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Trenbolone is a mogger compound, the ROI is insane if ran correctly but does come with a fair share of side effects
In this guide I will be explaining what tren is, its unique properties, side effects, and anciliries to take while running this roid
Trenbolone Overview
Trenbolone is a synthetic steroid not naturally occurring in humans, it is a 19 nor steroid derived from nandrolone. The chemical structure of trenbolone is unique, possessing a non-present carbon 19 atom and 3 double bonds located at carbons 4, 9, and 11. These properties in the chemical structure is what causes trenbolone to exhibit its high affinity to the AR, specifically the removal of the carbon 19 methyl group. The three double bonds on tren’s steroid core makes the molecule very rigid, combining this with the fact that it is a 19 nor meaning the C19 methyl group is missing makes it not a substrate for the aromatase enzyme. This triene shape also makes it resistant to 5 alpha reductase; this is because the electrons are delocalized across the conjugated double bonds, this helps the C4 double bond in the A ring resist 5AR thus yielding no DHT.
Tren obviously is much more potent than testosterone and has a higher binding affinity to the AR, like i said earlier this is because of the C19 not being present in tren’s molecule along with the triene structure. Tren has a similar binding affinity to dihydrotestosterone. Trenblone also has a slower dissociation rate from the androgen receptor which prolongs the receptor activation which enhances androgenic signaling. Trenbolone goes through genomic and non genomic pathways. Obviously the genomic pathway goes as follows: trenbolone enters the cytoplasm of a cell then binds to the ligand binding domain of the androgen receptor. The androgen receptor dissociates from chaperone proteins, dimerizes then translocates to the nucleus. Here it binds to AREs, recruits coactivators then alters the gene transcription and pumps out a biological effect. It's all simple stuff because tren is an androgen and goes through a lot of the same pathways endogenous androgens would go through. Tren also exerts its classical AR signaling at low concentrations so you don't need a lot of tren to get results.
On the topic of genomic signalling, Tren’s unique effects on the AR come from its chemical structure. This is obvious but when an androgen binds to the ligand binding domain of the AR it changes shape and recruits co activators through the formation of AF2. This is a hydrophobic groove in the receptor that allows for coactivator proteins to bind via amino acid sequences which help activate androgenic signaling. The AR also interacts with its own AF2 via the N terminal domain binding to the AF2 that can stabilize the AR and allow for longer signaling. Ligands change the receptor shape once bound to the receptors so tren could theoretically alter the AF2 more favorably compared to other androgens. Tren’s chemical structure could potentially alter the AF2 because once an androgen is in the LBD, helix 12 keeps it inside like a door, this is where the AF2 is formed. Tren could potentially make a better geometric place in the AF2 for coactivators and N terminal domain binding. Given tren’s strong androgenic signaling and enhanced effects this is very well the case.
Obviously being an androgen it can bind to mARs and activate downstream kinase cascades that are associated with muscle protein synthesis such as PI3K/akt/mTOR and MAPK/ERK. It also stabilizes β catenin which then helps with follistatin production which can antagonize myostatin on top of the androgen inhibiting myostatin directly by binding to the AR. Also PI3K/akt activation will of course inhibit foxO which will then drop production of degrading proteins such as MuRF and atrogin 1. The local IGF1 made from tren will also lead down into mTOR via the IGF1R. I'd recommend combining tren with something like oxymetholone so that the trenbolone occupies genomic AR signalling and the oxymetholone can handle non genomic signaling.
The fact that it doesn't aromatise makes you have nice dry gains. This is another reason why tren is the mogger cutting steroid that it is, along with GR antagonism and nutrient partitioning. Another cool thing about tren is that it may bind to the mineralocorticoid receptor, this of course helps with bloat as it antagonizes aldosterone. This may be a potential benefit because as we know tren has affinity to progesterone and glucocorticoid receptors and the mineralocorticoid receptor is in the same receptor family as those two and the AR. It's not crazy to assume that tren has an antagonist effect on the MR. Especially when this was observed in vitro upon taking tren’s cytotoxicity limit of 2.29 µM and finding activity for the mineralocorticoid receptor at concentrations lower than that, implying that its actual trenbolone activity rather than cell damage.
Tren has a low binding affinity to SHBG this allows way more of the hormone to be free and bind to ARs in target cells. This is why you always want to stay on the lower end of dosing when using tren, the number may look small but due to this property it's doing a lot more than you might think just looking at the dosing number.
Trenbolone enhances wnt pathway signalling via upregulation of β catenin and inhibition of notch pathways which antagonize wnt. This is obviously important as wnt is a growth pathway that is present in muscle and bone.
Tren enters myocyte/mesenchymal precursor cell → tren exerts negative effects on GSK3 and upregulates Numb via Tcf2/Lef gene transcription → more β catenin to exert his effects via wnt pathway and notch inhibition for further wnt signaling → muscle anabolism and mesenchymal precursor cells going down myogenesis lineage
In vivo it was shown to enhance this pathway using fish fins. Studies have observed this enhancement in myoblasts but we can also attribute this same mechanism to osteoblasts.
Trenbolone binds AR → more wnt ligand is created → wnt binds to frizzled receptors thus stabilizing β catenin → β catenin levels were raised because of trenbolones negative effects on GSK3 → more β catenin to bind with tren/AR complex as co activators → translocation to nucleus → osteogenetic gene transcription such as runx2 and osterix
Further adding on this, wnt upregulates OPG via TCF/LEC/tnfrsf11b gene transcription which further prevents resorption
Speaking of trenbolone acting on bone, it was shown that in studies using rats who were skeletally mature and who were orchiectomized that trenbolone partially or completely countered the bone loss from hypogonadism and maintained bone strength, enhancing the femoral neck in the rats. It's also good to note that in the presence of AIs the BMD caused from tren didn't get messed up at all which means that trenbolone doesn't need to aromatase into e2 to exert its effects on bone
In a study done on ORX rats testosterone and trenbolone were administered in the presence of anastrozole. The osteoclast surface was reduced in both groups however AI administration with test reduced the osteoclast surface reducing effects of test to that of SHAMs, while AI coadministration with tren resulted in zero reduction in trens osteoclast surface reducing effects. Maximum breaking loads of the femoral neck exceeded SHAMs in ORX + tren rats and was comparable to SHAMs in ORX + tren + AI rats. LABC mass was also greater in rats treated with tren compared to SHAMs, roughly 38-42% greater.
In the same study TE and tren also reduced the osteoblast surfaces in the bone that were caused from a high turnover rate due to ORX. This shows that the androgens reduced the turnover rate in hypogonadal rats and like the first statement, AI administration didn't change reduce trens effects
Gluticorticoid Receptor Antagonist
This is why tren mogs so hard while cutting, it just blocks the catabolic effects of cortisol. Tren decreases the amount of GR mRNA and also binds to the GR further antagonizing cortisol
The anti catabolic effects are not only in muscle as they are expressed in bone. GRs inhabit bone cells and cortisol can bind with them and increase sclerostin secretion and disrupt the OPG/RANKL axis and inhibits the wnt pathway which ultimately leads to osteoclastogenesis and bone resorption. Once tren enters this whole cascade just gets antagonized
IGF-1
Trenbolone makes you more sensitive to IGF1, in rat satellite cells it was shown that rats treated with tren had way more proliferation. In contrast it was shown that if you place tren directly in the medium of cultured satellite cells it did not have any proliferative effects. Comparing this with satellite cells from rats treated with tren who had greater proliferative effects to FGF and IGF1 clearly showing an increased sensitivity. So on top of potent paracrine IGF1 signalling, it contributes to increased systemic IGF1.
IGF1 also contributes to bone via IGF1R/akt+PI3K/mTOR activation which leads to the proliferation of osteblasts
Nutritional Parting
This refers to how much of your nutrients/calories goes to muscle or fat. Trenbolone has insane nutrient partitioning properties that make it so you can eat in a surplus and hardly gain any fat at all as it overwhelming goes to muscle tissue
This is caused by the increase of nitrogen retention in muscle tissues which drives better intake of nutrients to muscle. Tren also has positive effects on lipolysis so therefore there's not gonna be as much nutrients being stored as fat. Tren also improves glycogen stores in muscles which naturally makes you recover faster.
For an example let's say before tren 60% of your nutrients went to fat and 40% of it went to muscle, while on tren 70% will go to muscle while 30% will go to fat.
Side Effects
Gyno
Tren's strong affinity for the PR increases prolactin which can cause gyno
Neurotoxicity
Tren is neurotoxic. It can shorten neurites and cause neuron apoptosis. Tren accumulates a lot in your hippocampus, causing hippocampal neuron death and raising Aβ42 and caspase 3 levels essentially degrading your brain through the same pathways as alzheimer's disease. Along with that it also disrupts presenilin 1 and this is where it can mess with APP peptide production which leads to the upregulation of Aβ42 like we stated earlier.
Tren accumulates in hippocampus → decreases presenilin 1 and upregulates Aβ42 and caspase 3 activity → neurodegeneration/neuron apoptosis
Going along with AD like symptoms we have the fact that tren exacerbates TNF-α and IL1β inflammation which leads to activation of the hepatic IL6 inflammatory pathway which enhances release of LCN2 which then comes into the brain and expresses itself in the mPFC. This neurovisceral circuit eventually leads to the deposition of Aβ proteins which as you know is the pathway of which AD takes its toll.
Tren exacerbates TNF-α and IL1β → triggers hepatic IL6 inflammatory pathway → enhanced secretion of LCN2 which expresses itself in the brain → Aβ deposition → neurodegeneration
Tren increases neuroinflammation such as NLRP3 inflammasome, IL-6, IL-1α, and IL-1β as well as increasing proapoptotic proteins like caspase 3/7 and Bax while lowering anti apoptotic proteins such as DJ-1 and Bcl-1
Tren enters CNS → NLRP3 IL6 IL-1α IL-1β caspase 3/7 Bax increase Bcl-1 and DJ-1 decrease, tyrosine hydrolase reduction → domaminergic neuronal death worsening/neuronal apoptosis/dopamine pathway damage/substantia nigra damage
Tren causes declined mitochondrial function and causes lactate dehydrogenase release. This release is a marker of membrane damage and cell death. This mitochondrial decline comes from the neuroinflammatory cytokines I listed above, inhibition of neuroprotective proteins, as well as AR mediated pathways and oxidative stress.
Trensomnia is an effect you've heard thrown around if you know anything about tren, this is caused from an upregulation of orexin signaling which promotes wakefulness. Tren also disturbs motoneuron development and locomotion.
Tren enters CNS → upregulates orexin signaling → insomnia phenotype
I don't really know where to put this so fuck it, the thyroid is close enough to the brain. Tren suppresses t4 → t3 conversion
Tren creates a ton of ROS via an upregulation of nox, specifically hydroxyl radicals, the most destructive free radical, thus throwing off the balance of oxidants and antioxidants which then leads to oxidative stress.
Mental Side Effects
Tren can make you aggressive, this mechanism acts on NMDARs. Tren reduces these receptors in your hippocampus as well as your hypothalamus.
Anxiety is also a possibility on tren, the proposed mechanism is altering of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex. This can disrupt cortical glutamate making it increase and cause excitotoxicity and localized hypo reactivity which is linked to anxiety and social avoidance
Trenbolone suppresses endogenous testosterone and disturbs the TACR3 pathway in the hippocampus and thus inducing abnormal synaptic transmission signaling in the hippocampus, down regulation of synaptic proteins: PSD95, syn, gephyrin as well as metabolic imbalance in glutamate/GABA signaling. However having a test base will alleviate this, as observed in the rat study
Tren crosses BBB → down regulation of PSD95, syn, gephyrin, GABA/glutamate metabolic imbalance, down regulation of TACR3 hippocampus pathway → impaired synaptic plasticity and emotion regulation → anxiety behavior
Tren crosses BBB and disrupts maturation of oligodendrocytes → increase in glutamate and disruption of formation of the myelin sheath → excitotoxicity in the mPFC → anxiety
Trenbolone causes GABAergic disinhibition, tren can bind with GABAa receptors and make them go under allosteric modulation, modification of neuronal transmission and the activation and sensitivity of these receptors. As we know GABA is the inhibitory signals in your brain that calms your CNS, tren can basically change the way these receptors work to make you lower inhib and more aggressive
Tren crosses BBB → binds to GABAa receptors in the CNS → allosteric modulation of GABAa receptors → lower inhib/less inhibitory signals in CNS → impulsive behavior
Trenbolone of course suppresses the HPG axis and in a mice study this was found to disrupt sex steroids of course, altering AR and ERa levels in the testis. Tren also caused more dominant social behavior and stronger sexual attraction to females as well as males, when they checked for markers all they could find was increased c-Nos in the mPFC and the BLA.
Tren suppresses HPG axis → abnormal AR and ERa levels → disrupted sex steroid signaling → signaling in mPFC and BLA → social dominance and gayness
Proposed mechanism of course, but this could be how tren makes you gay.
19 nors cause shifts in density of serotonergic receptors in multiple regions in the brain, downregulation of 5HT1B receptor density in the hippocampus and in the medial globus pallidas. Upregulation of 5HT2 receptor density in the nucleus accumbens. Shifts in serotonergic receptors were also seen in more regions of the brain
By down regulating the 5HT1B it makes your serotonin brake not function properly and unable to inhibit impulsive behaviors, while this is happening an upregulation of 5HT2 makes it so that your reward system is hypersensitive making neutral things seem threatening and intense
Tren crosses BBB → up and down regulation of 5HT2 and 5HT1B serotonin receptors in multiple regions of the brain → Decreased impulse control and aggressive behavior
Tren isn't limited to mice studies when observing aggression, there have been studies that survey AAS users and have found a dose dependent relationship between trenbolone and verbal aggression
“After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression.”
“Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues.”
Tren not being to aromatase means there is pure androgenic signalling on your cardiovascular system without the added benefit of estrogen NO release and estrogen driven nephroprotectin. This results in high blood pressure which can also cause kidney problems. Although high creatinine is an issue, it doesn't really do much here as 19 nor cycles are relatively short.
Because estrogen cannot be provided from the trenbolone ligand, the androgenic effects on lipids is severe. Tren wrecks HDL while also raising LDL. This can lead to your arteries getting clogged and increasing workload on your cardiovascular system which therefore will lead to LVH.
Hematocrit will rise while on androgens and your blood will get thick, this is an issue because of clotting and more strain on the cardiovascular system.
Tren signals the adrenergic system which causes an overactive SNS which can narrow blood vessels forcing your heart to pump faster which leads to fast resting heart rate.
Tren also has hepatotoxic effects which in case reports was seen with severe transaminasemia which is a marker for AST/ALT enzymes in the bloodstream indicating hepatocyte injury. Also having hyperbilirubinemia caused by disrupted bile flow and also renal damage.
Liver markers showed cholestasis, sinusoidal dilation and cholangitis like changes, all are markers of hepatocyte injury and cholestatic injury.
All in all, trenbolone effects on the liver can be caused from oxidative stress, impaired bile export and disrupted hepatocyte transporter activity.
Memantine is an uncompetitive NMDA receptor antagonist that antagonizes glutamate which helps against neurodegeneration trenbolone will cause from glutamate excitotoxicity
Cerebrolysin - One Course Post Cycle
Peptide derived from pig brain with a low molecular weight allowing it to cross the BBB easily. Upregulates shh pathway to induce neural progenitor cell proliferation and oligodendrogenesis and neurogenesis. It mimics and stimulates neurotrophic growth factors in your brain like NTF3 and BDNF.
Cerebrolysin had been used for AD, traumatic brain injury and strokes with significantly beneficial results, should be able to cleave tren neurotoxicity adequately
Melatonin 100mg+
Sleep hormone that acts on MT1 and MT2 receptors to regulate circadian rhythm. At megadoses it can be a powerful antioxidant. It is a direct free radical scavenger and can neutralize a lot of ROS and RNS. It also stimulates a few antioxidant enzymes further pushing its antioxidant abilities.
Melatonin also binds to mt1 receptors on the mitochondrial membrane and dampening caspase activation through downstream pathways. Melatonin stimulates oxidative phosphorylation and promotes ATP production in neuronal and hepatocyte mitochondria.
Very mogger molecule that keeps cells safe from oxidative stress whilst also neutralizing ROS and RNS. One more thing about melatonin is that it inhibits NLRP3 inflammasome which is activated by tren and is linked to apoptosis
Propronal 10mg
Competitive nonselective beta blocker that acts on receptors β1 and β2 which can help reduce adrenaline and noradrenaline signaling and dampen the somatic feedback loop and its anxiety symptoms, thus reducing impulsive behavior and aggression and could potentially help with night sweats due to a relaxed SNS and suppressed somatic feedback loop
DORAs
Dual orexin receptor antagonists, targets both OX1R and OX2R to inhibit wakefulness signals of the orexin system that induce insomnia. No dependency issues arise either.
Empagliflozin 10mg
Increases mitochondria ATP production and reduces oxidative stress making the mitochondria more efficient
NACET 100mg
N-acetylcysteine with a longer half life and better bioavailability, is a precursor to glutathione which is your body's natural antioxidant. Crosses the BBB which allows for glutathione production in the CNS
9-Me-BC
Monoamine oxidase inhibitor that upregulates tyrosine hydrolase which can lead to dopaminergic synthesis. It also creates an anti inflammatory environment by decreasing inflammatory cytokines and receptors.
In studies it was shown to reverse the domaminergic neurotoxicity from MPP and make the dopaminergic immunoreactivity cells in the striata nigra go back to normal levels after exposed neurotoxicity.
Also reduces caspase 3 activity and increases ATP content and obviously dopaminergic neuron differentiation was increased
Astaxanthin
Carotenoid that has antioxidant benefits, crosses the BBB and suppresses the NF-κB pathway and also production of inflammatory cytokines. Linking to the membrane from inside to outside allows for better biological activity. Of course donates electrons to free radicals to neutralize them as well
Cardiovascular/Liver/Kidney protection
Telmisartan 160mg
Angiotensin 2 blocker that acts on angiotensin type 1 receptors to minimize vasoconstriction caused from overactive RAAS, also nice Insulin sensitivity bonus due to partial agonism of the PPARγ
Tadalafil 5-10mg
PDE5 Inhibitor that blocks the PDE5 enzyme from breaking down cGMP which lets smooth muscle relax and blood flow commence easier
Nebivolol 5-10mg
Highly selective β1 receptor antagonist that antagonizes adrenergic signaling in the heart, therefore lowering resting heart rate. Also has antihypertensive properties due to being a β3 agonist which stimulates nitric oxide release and vasodilation
Eplerenone 50mg
Selective MR antagonist that antagonizes aldosterone, thus stopping aldosterone from inducing myocardial fibrosis
Tudca 500mg
Bile acid that helps maintain bile flow to avoid cholestasis and also supports hepatocytes from ER stress by folding proteins
NACET 100mg
Cysteine → glutathione conversion used for antioxidant and hepatoprotection
Empagliflozin 10mg
SGLT2 inhibitor that handles glucose as well as having kidney protective properties by reducing workload placed on the kidneys. Cardio protection benefits are also included
Rupatadine 10mg
Histamine antagonist with selective peripheral H1 receptor antagonist activity blocking the receptors of PAF. This helps for tren’s PAF inflammatory signalling, you can throw this into a lot of cycles with AAS due to the inflammation
Pentoxifylline 400mg
Phosphodiesterase inhibitor that makes blood less vicious and makes red blood cells more flexible via increase ethyrocyte ATP and cyclic nucleotide levels which allows blood to travel through narrow passages which will be helpful with raised hematocrit from tren
Pemafibrate 0.2mg
The superior fibrate that selectively binds to PPARa for serum triglyceride reduction as well as increasing HDL. Helps liver function and doesn't place strain on the kidneys and can be taken along side with statins due to low drug interactions
Lipids/Prolactin/Thyroid
Pitavastatin 2-4mg
HMG-CoA reductase Inhibitor which is the enzyme used by the liver to make cholesterol. This causes an inhibition of mevalonic acid which then upregulates LDL receptors in hepatocytes to make up for the inhibition. These extra receptors grab LDL from your blood stream which leads to LDL catabolism. Also increases and enhances HDL
Ezetimibe 10mg
NPC1L1 protein blocker that inhibits the reabsorption of cholesterol from the small intestine and inhibiting the amount of cholesterol hepatocytes can use, thus making your body use circulating cholesterol which can help with high cholesterol especially when paired with a statin
P5P 200mg
L-tyrosine → L-DOPA → dopamine is the pathway in which p5p enhances. P5P is the active coenzyme b6 and helps L-DOPA convert into dopamine and bind to d2 receptors in the hypothalamus which puts a brake on prolactin secretion when reaching the pituitary
Cabergolin 0.5 - 2.5mg
D2 agonist that binds to dopamine receptors in the anterior pituitary and puts a brake on prolactin secretion
T4 + T3
Inactive and active thyroid hormones that control metabolic rate among other things. Since your conversion will slow down we'll just supplement these. Make sure to taper off nearing the end of your cycle and that your natural production of these hormones have rebounded
Hair/Skin
Isotretinoin 10-40mg
Shrinks sebaceous glands and reduces sebum production for no acne
Topical Estriol
Nice addition to any skincare routine, acts on ERs in the skin to promote elastin synthesis and is especially nice when used with retinoids
ru58841/kx-826
Both topical anti androgens, works by competing for androgen receptors and binding them so androgens can't bind to the AR, essential for compounds that bypass 5 alpha reduction.
Although tren itself isn't that androgenic due to the methyl group removal, these are still a nice edition if you plan on running DHT derivatives on your cycle
Esters
Trenbolone Acetate
Fastest acting ester with a half life of approximately 1-2 days, This calls for ED or EOD injections
Trenbolone Enanthate
Longer acting ester with a half life of approximately 11 days, would still make injections EOD at least so you don't inject a ton of androgens at once and experience worse sides
Trenbolone Hexahydrolbenzoylcarbonate
Between the two other esters with a half life of approximately 8 days, nobody runs this ester due to it not being pharmaceutically produced anymore
Conclusion
Hopefully you learned something and truly imagine the CNS destruction of tren but also the high ROI when managed correctly
Trenbolone is a synthetic steroid not naturally occurring in humans, it is a 19 nor steroid derived from nandrolone. The chemical structure of trenbolone is unique, possessing a non-present carbon 19 atom and 3 double bonds located at carbons 4, 9, and 11. These properties in the chemical structure is what causes trenbolone to exhibit its high affinity to the AR, specifically the removal of the carbon 19 methyl group. The three double bonds on tren’s steroid core makes the molecule very rigid, combining this with the fact that it is a 19 nor meaning the C19 methyl group is missing makes it not a substrate for the aromatase enzyme. This triene shape also makes it resistant to 5 alpha reductase; this is because the electrons are delocalized across the conjugated double bonds, this helps the C4 double bond in the A ring resist 5AR thus yielding no DHT.
Tren obviously is much more potent than testosterone and has a higher binding affinity to the AR, like i said earlier this is because of the C19 not being present in tren’s molecule along with the triene structure. Tren has a similar binding affinity to dihydrotestosterone. Trenblone also has a slower dissociation rate from the androgen receptor which prolongs the receptor activation which enhances androgenic signaling. Trenbolone goes through genomic and non genomic pathways. Obviously the genomic pathway goes as follows: trenbolone enters the cytoplasm of a cell then binds to the ligand binding domain of the androgen receptor. The androgen receptor dissociates from chaperone proteins, dimerizes then translocates to the nucleus. Here it binds to AREs, recruits coactivators then alters the gene transcription and pumps out a biological effect. It's all simple stuff because tren is an androgen and goes through a lot of the same pathways endogenous androgens would go through. Tren also exerts its classical AR signaling at low concentrations so you don't need a lot of tren to get results.
On the topic of genomic signalling, Tren’s unique effects on the AR come from its chemical structure. This is obvious but when an androgen binds to the ligand binding domain of the AR it changes shape and recruits co activators through the formation of AF2. This is a hydrophobic groove in the receptor that allows for coactivator proteins to bind via amino acid sequences which help activate androgenic signaling. The AR also interacts with its own AF2 via the N terminal domain binding to the AF2 that can stabilize the AR and allow for longer signaling. Ligands change the receptor shape once bound to the receptors so tren could theoretically alter the AF2 more favorably compared to other androgens. Tren’s chemical structure could potentially alter the AF2 because once an androgen is in the LBD, helix 12 keeps it inside like a door, this is where the AF2 is formed. Tren could potentially make a better geometric place in the AF2 for coactivators and N terminal domain binding. Given tren’s strong androgenic signaling and enhanced effects this is very well the case.
Obviously being an androgen it can bind to mARs and activate downstream kinase cascades that are associated with muscle protein synthesis such as PI3K/akt/mTOR and MAPK/ERK. It also stabilizes β catenin which then helps with follistatin production which can antagonize myostatin on top of the androgen inhibiting myostatin directly by binding to the AR. Also PI3K/akt activation will of course inhibit foxO which will then drop production of degrading proteins such as MuRF and atrogin 1. The local IGF1 made from tren will also lead down into mTOR via the IGF1R. I'd recommend combining tren with something like oxymetholone so that the trenbolone occupies genomic AR signalling and the oxymetholone can handle non genomic signaling.
The fact that it doesn't aromatise makes you have nice dry gains. This is another reason why tren is the mogger cutting steroid that it is, along with GR antagonism and nutrient partitioning. Another cool thing about tren is that it may bind to the mineralocorticoid receptor, this of course helps with bloat as it antagonizes aldosterone. This may be a potential benefit because as we know tren has affinity to progesterone and glucocorticoid receptors and the mineralocorticoid receptor is in the same receptor family as those two and the AR. It's not crazy to assume that tren has an antagonist effect on the MR. Especially when this was observed in vitro upon taking tren’s cytotoxicity limit of 2.29 µM and finding activity for the mineralocorticoid receptor at concentrations lower than that, implying that its actual trenbolone activity rather than cell damage.
Tren has a low binding affinity to SHBG this allows way more of the hormone to be free and bind to ARs in target cells. This is why you always want to stay on the lower end of dosing when using tren, the number may look small but due to this property it's doing a lot more than you might think just looking at the dosing number.
Trenbolone enhances wnt pathway signalling via upregulation of β catenin and inhibition of notch pathways which antagonize wnt. This is obviously important as wnt is a growth pathway that is present in muscle and bone.
Tren enters myocyte/mesenchymal precursor cell → tren exerts negative effects on GSK3 and upregulates Numb via Tcf2/Lef gene transcription → more β catenin to exert his effects via wnt pathway and notch inhibition for further wnt signaling → muscle anabolism and mesenchymal precursor cells going down myogenesis lineage
In vivo it was shown to enhance this pathway using fish fins. Studies have observed this enhancement in myoblasts but we can also attribute this same mechanism to osteoblasts.
Trenbolone binds AR → more wnt ligand is created → wnt binds to frizzled receptors thus stabilizing β catenin → β catenin levels were raised because of trenbolones negative effects on GSK3 → more β catenin to bind with tren/AR complex as co activators → translocation to nucleus → osteogenetic gene transcription such as runx2 and osterix
Further adding on this, wnt upregulates OPG via TCF/LEC/tnfrsf11b gene transcription which further prevents resorption
Speaking of trenbolone acting on bone, it was shown that in studies using rats who were skeletally mature and who were orchiectomized that trenbolone partially or completely countered the bone loss from hypogonadism and maintained bone strength, enhancing the femoral neck in the rats. It's also good to note that in the presence of AIs the BMD caused from tren didn't get messed up at all which means that trenbolone doesn't need to aromatase into e2 to exert its effects on bone
In a study done on ORX rats testosterone and trenbolone were administered in the presence of anastrozole. The osteoclast surface was reduced in both groups however AI administration with test reduced the osteoclast surface reducing effects of test to that of SHAMs, while AI coadministration with tren resulted in zero reduction in trens osteoclast surface reducing effects. Maximum breaking loads of the femoral neck exceeded SHAMs in ORX + tren rats and was comparable to SHAMs in ORX + tren + AI rats. LABC mass was also greater in rats treated with tren compared to SHAMs, roughly 38-42% greater.
In the same study TE and tren also reduced the osteoblast surfaces in the bone that were caused from a high turnover rate due to ORX. This shows that the androgens reduced the turnover rate in hypogonadal rats and like the first statement, AI administration didn't change reduce trens effects
Gluticorticoid Receptor Antagonist
This is why tren mogs so hard while cutting, it just blocks the catabolic effects of cortisol. Tren decreases the amount of GR mRNA and also binds to the GR further antagonizing cortisol
The anti catabolic effects are not only in muscle as they are expressed in bone. GRs inhabit bone cells and cortisol can bind with them and increase sclerostin secretion and disrupt the OPG/RANKL axis and inhibits the wnt pathway which ultimately leads to osteoclastogenesis and bone resorption. Once tren enters this whole cascade just gets antagonized
IGF-1
Trenbolone makes you more sensitive to IGF1, in rat satellite cells it was shown that rats treated with tren had way more proliferation. In contrast it was shown that if you place tren directly in the medium of cultured satellite cells it did not have any proliferative effects. Comparing this with satellite cells from rats treated with tren who had greater proliferative effects to FGF and IGF1 clearly showing an increased sensitivity. So on top of potent paracrine IGF1 signalling, it contributes to increased systemic IGF1.
IGF1 also contributes to bone via IGF1R/akt+PI3K/mTOR activation which leads to the proliferation of osteblasts
Nutritional Parting
This refers to how much of your nutrients/calories goes to muscle or fat. Trenbolone has insane nutrient partitioning properties that make it so you can eat in a surplus and hardly gain any fat at all as it overwhelming goes to muscle tissue
This is caused by the increase of nitrogen retention in muscle tissues which drives better intake of nutrients to muscle. Tren also has positive effects on lipolysis so therefore there's not gonna be as much nutrients being stored as fat. Tren also improves glycogen stores in muscles which naturally makes you recover faster.
For an example let's say before tren 60% of your nutrients went to fat and 40% of it went to muscle, while on tren 70% will go to muscle while 30% will go to fat.
Side Effects
Gyno
Tren's strong affinity for the PR increases prolactin which can cause gyno
Neurotoxicity
Tren is neurotoxic. It can shorten neurites and cause neuron apoptosis. Tren accumulates a lot in your hippocampus, causing hippocampal neuron death and raising Aβ42 and caspase 3 levels essentially degrading your brain through the same pathways as alzheimer's disease. Along with that it also disrupts presenilin 1 and this is where it can mess with APP peptide production which leads to the upregulation of Aβ42 like we stated earlier.
Tren accumulates in hippocampus → decreases presenilin 1 and upregulates Aβ42 and caspase 3 activity → neurodegeneration/neuron apoptosis
Going along with AD like symptoms we have the fact that tren exacerbates TNF-α and IL1β inflammation which leads to activation of the hepatic IL6 inflammatory pathway which enhances release of LCN2 which then comes into the brain and expresses itself in the mPFC. This neurovisceral circuit eventually leads to the deposition of Aβ proteins which as you know is the pathway of which AD takes its toll.
Tren exacerbates TNF-α and IL1β → triggers hepatic IL6 inflammatory pathway → enhanced secretion of LCN2 which expresses itself in the brain → Aβ deposition → neurodegeneration
Tren increases neuroinflammation such as NLRP3 inflammasome, IL-6, IL-1α, and IL-1β as well as increasing proapoptotic proteins like caspase 3/7 and Bax while lowering anti apoptotic proteins such as DJ-1 and Bcl-1
Tren enters CNS → NLRP3 IL6 IL-1α IL-1β caspase 3/7 Bax increase Bcl-1 and DJ-1 decrease, tyrosine hydrolase reduction → domaminergic neuronal death worsening/neuronal apoptosis/dopamine pathway damage/substantia nigra damage
Tren causes declined mitochondrial function and causes lactate dehydrogenase release. This release is a marker of membrane damage and cell death. This mitochondrial decline comes from the neuroinflammatory cytokines I listed above, inhibition of neuroprotective proteins, as well as AR mediated pathways and oxidative stress.
Trensomnia is an effect you've heard thrown around if you know anything about tren, this is caused from an upregulation of orexin signaling which promotes wakefulness. Tren also disturbs motoneuron development and locomotion.
Tren enters CNS → upregulates orexin signaling → insomnia phenotype
I don't really know where to put this so fuck it, the thyroid is close enough to the brain. Tren suppresses t4 → t3 conversion
Tren creates a ton of ROS via an upregulation of nox, specifically hydroxyl radicals, the most destructive free radical, thus throwing off the balance of oxidants and antioxidants which then leads to oxidative stress.
Mental Side Effects
Tren can make you aggressive, this mechanism acts on NMDARs. Tren reduces these receptors in your hippocampus as well as your hypothalamus.
Anxiety is also a possibility on tren, the proposed mechanism is altering of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex. This can disrupt cortical glutamate making it increase and cause excitotoxicity and localized hypo reactivity which is linked to anxiety and social avoidance
Trenbolone suppresses endogenous testosterone and disturbs the TACR3 pathway in the hippocampus and thus inducing abnormal synaptic transmission signaling in the hippocampus, down regulation of synaptic proteins: PSD95, syn, gephyrin as well as metabolic imbalance in glutamate/GABA signaling. However having a test base will alleviate this, as observed in the rat study
Tren crosses BBB → down regulation of PSD95, syn, gephyrin, GABA/glutamate metabolic imbalance, down regulation of TACR3 hippocampus pathway → impaired synaptic plasticity and emotion regulation → anxiety behavior
Tren crosses BBB and disrupts maturation of oligodendrocytes → increase in glutamate and disruption of formation of the myelin sheath → excitotoxicity in the mPFC → anxiety
Trenbolone causes GABAergic disinhibition, tren can bind with GABAa receptors and make them go under allosteric modulation, modification of neuronal transmission and the activation and sensitivity of these receptors. As we know GABA is the inhibitory signals in your brain that calms your CNS, tren can basically change the way these receptors work to make you lower inhib and more aggressive
Tren crosses BBB → binds to GABAa receptors in the CNS → allosteric modulation of GABAa receptors → lower inhib/less inhibitory signals in CNS → impulsive behavior
Trenbolone of course suppresses the HPG axis and in a mice study this was found to disrupt sex steroids of course, altering AR and ERa levels in the testis. Tren also caused more dominant social behavior and stronger sexual attraction to females as well as males, when they checked for markers all they could find was increased c-Nos in the mPFC and the BLA.
Tren suppresses HPG axis → abnormal AR and ERa levels → disrupted sex steroid signaling → signaling in mPFC and BLA → social dominance and gayness
Proposed mechanism of course, but this could be how tren makes you gay.
19 nors cause shifts in density of serotonergic receptors in multiple regions in the brain, downregulation of 5HT1B receptor density in the hippocampus and in the medial globus pallidas. Upregulation of 5HT2 receptor density in the nucleus accumbens. Shifts in serotonergic receptors were also seen in more regions of the brain
By down regulating the 5HT1B it makes your serotonin brake not function properly and unable to inhibit impulsive behaviors, while this is happening an upregulation of 5HT2 makes it so that your reward system is hypersensitive making neutral things seem threatening and intense
Tren crosses BBB → up and down regulation of 5HT2 and 5HT1B serotonin receptors in multiple regions of the brain → Decreased impulse control and aggressive behavior
Tren isn't limited to mice studies when observing aggression, there have been studies that survey AAS users and have found a dose dependent relationship between trenbolone and verbal aggression
“After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression.”
“Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues.”
Tren not being to aromatase means there is pure androgenic signalling on your cardiovascular system without the added benefit of estrogen NO release and estrogen driven nephroprotectin. This results in high blood pressure which can also cause kidney problems. Although high creatinine is an issue, it doesn't really do much here as 19 nor cycles are relatively short.
Because estrogen cannot be provided from the trenbolone ligand, the androgenic effects on lipids is severe. Tren wrecks HDL while also raising LDL. This can lead to your arteries getting clogged and increasing workload on your cardiovascular system which therefore will lead to LVH.
Hematocrit will rise while on androgens and your blood will get thick, this is an issue because of clotting and more strain on the cardiovascular system.
Tren signals the adrenergic system which causes an overactive SNS which can narrow blood vessels forcing your heart to pump faster which leads to fast resting heart rate.
Tren also has hepatotoxic effects which in case reports was seen with severe transaminasemia which is a marker for AST/ALT enzymes in the bloodstream indicating hepatocyte injury. Also having hyperbilirubinemia caused by disrupted bile flow and also renal damage.
Liver markers showed cholestasis, sinusoidal dilation and cholangitis like changes, all are markers of hepatocyte injury and cholestatic injury.
All in all, trenbolone effects on the liver can be caused from oxidative stress, impaired bile export and disrupted hepatocyte transporter activity.
Memantine is an uncompetitive NMDA receptor antagonist that antagonizes glutamate which helps against neurodegeneration trenbolone will cause from glutamate excitotoxicity
Cerebrolysin - One Course Post Cycle
Peptide derived from pig brain with a low molecular weight allowing it to cross the BBB easily. Upregulates shh pathway to induce neural progenitor cell proliferation and oligodendrogenesis and neurogenesis. It mimics and stimulates neurotrophic growth factors in your brain like NTF3 and BDNF.
Cerebrolysin had been used for AD, traumatic brain injury and strokes with significantly beneficial results, should be able to cleave tren neurotoxicity adequately
Melatonin 100mg+
Sleep hormone that acts on MT1 and MT2 receptors to regulate circadian rhythm. At megadoses it can be a powerful antioxidant. It is a direct free radical scavenger and can neutralize a lot of ROS and RNS. It also stimulates a few antioxidant enzymes further pushing its antioxidant abilities.
Melatonin also binds to mt1 receptors on the mitochondrial membrane and dampening caspase activation through downstream pathways. Melatonin stimulates oxidative phosphorylation and promotes ATP production in neuronal and hepatocyte mitochondria.
Very mogger molecule that keeps cells safe from oxidative stress whilst also neutralizing ROS and RNS. One more thing about melatonin is that it inhibits NLRP3 inflammasome which is activated by tren and is linked to apoptosis
Propronal 10mg
Competitive nonselective beta blocker that acts on receptors β1 and β2 which can help reduce adrenaline and noradrenaline signaling and dampen the somatic feedback loop and its anxiety symptoms, thus reducing impulsive behavior and aggression and could potentially help with night sweats due to a relaxed SNS and suppressed somatic feedback loop
DORAs
Dual orexin receptor antagonists, targets both OX1R and OX2R to inhibit wakefulness signals of the orexin system that induce insomnia. No dependency issues arise either.
Empagliflozin 10mg
Increases mitochondria ATP production and reduces oxidative stress making the mitochondria more efficient
NACET 100mg
N-acetylcysteine with a longer half life and better bioavailability, is a precursor to glutathione which is your body's natural antioxidant. Crosses the BBB which allows for glutathione production in the CNS
9-Me-BC
Monoamine oxidase inhibitor that upregulates tyrosine hydrolase which can lead to dopaminergic synthesis. It also creates an anti inflammatory environment by decreasing inflammatory cytokines and receptors.
In studies it was shown to reverse the domaminergic neurotoxicity from MPP and make the dopaminergic immunoreactivity cells in the striata nigra go back to normal levels after exposed neurotoxicity.
Also reduces caspase 3 activity and increases ATP content and obviously dopaminergic neuron differentiation was increased
Astaxanthin
Carotenoid that has antioxidant benefits, crosses the BBB and suppresses the NF-κB pathway and also production of inflammatory cytokines. Linking to the membrane from inside to outside allows for better biological activity. Of course donates electrons to free radicals to neutralize them as well
Cardiovascular/Liver/Kidney protection
Telmisartan 160mg
Angiotensin 2 blocker that acts on angiotensin type 1 receptors to minimize vasoconstriction caused from overactive RAAS, also nice Insulin sensitivity bonus due to partial agonism of the PPARγ
Tadalafil 5-10mg
PDE5 Inhibitor that blocks the PDE5 enzyme from breaking down cGMP which lets smooth muscle relax and blood flow commence easier
Nebivolol 5-10mg
Highly selective β1 receptor antagonist that antagonizes adrenergic signaling in the heart, therefore lowering resting heart rate. Also has antihypertensive properties due to being a β3 agonist which stimulates nitric oxide release and vasodilation
Eplerenone 50mg
Selective MR antagonist that antagonizes aldosterone, thus stopping aldosterone from inducing myocardial fibrosis
Tudca 500mg
Bile acid that helps maintain bile flow to avoid cholestasis and also supports hepatocytes from ER stress by folding proteins
NACET 100mg
Cysteine → glutathione conversion used for antioxidant and hepatoprotection
Empagliflozin 10mg
SGLT2 inhibitor that handles glucose as well as having kidney protective properties by reducing workload placed on the kidneys. Cardio protection benefits are also included
Rupatadine 10mg
Histamine antagonist with selective peripheral H1 receptor antagonist activity blocking the receptors of PAF. This helps for tren’s PAF inflammatory signalling, you can throw this into a lot of cycles with AAS due to the inflammation
Pentoxifylline 400mg
Phosphodiesterase inhibitor that makes blood less vicious and makes red blood cells more flexible via increase ethyrocyte ATP and cyclic nucleotide levels which allows blood to travel through narrow passages which will be helpful with raised hematocrit from tren
Pemafibrate 0.2mg
The superior fibrate that selectively binds to PPARa for serum triglyceride reduction as well as increasing HDL. Helps liver function and doesn't place strain on the kidneys and can be taken along side with statins due to low drug interactions
Lipids/Prolactin/Thyroid
Pitavastatin 2-4mg
HMG-CoA reductase Inhibitor which is the enzyme used by the liver to make cholesterol. This causes an inhibition of mevalonic acid which then upregulates LDL receptors in hepatocytes to make up for the inhibition. These extra receptors grab LDL from your blood stream which leads to LDL catabolism. Also increases and enhances HDL
Ezetimibe 10mg
NPC1L1 protein blocker that inhibits the reabsorption of cholesterol from the small intestine and inhibiting the amount of cholesterol hepatocytes can use, thus making your body use circulating cholesterol which can help with high cholesterol especially when paired with a statin
P5P 200mg
L-tyrosine → L-DOPA → dopamine is the pathway in which p5p enhances. P5P is the active coenzyme b6 and helps L-DOPA convert into dopamine and bind to d2 receptors in the hypothalamus which puts a brake on prolactin secretion when reaching the pituitary
Cabergolin 0.5 - 2.5mg
D2 agonist that binds to dopamine receptors in the anterior pituitary and puts a brake on prolactin secretion
T4 + T3
Inactive and active thyroid hormones that control metabolic rate among other things. Since your conversion will slow down we'll just supplement these. Make sure to taper off nearing the end of your cycle and that your natural production of these hormones have rebounded
Hair/Skin
Isotretinoin 10-40mg
Shrinks sebaceous glands and reduces sebum production for no acne
Topical Estriol
Nice addition to any skincare routine, acts on ERs in the skin to promote elastin synthesis and is especially nice when used with retinoids
ru58841/kx-826
Both topical anti androgens, works by competing for androgen receptors and binding them so androgens can't bind to the AR, essential for compounds that bypass 5 alpha reduction.
Although tren itself isn't that androgenic due to the methyl group removal, these are still a nice edition if you plan on running DHT derivatives on your cycle
Esters
Trenbolone Acetate
Fastest acting ester with a half life of approximately 1-2 days, This calls for ED or EOD injections
Trenbolone Enanthate
Longer acting ester with a half life of approximately 11 days, would still make injections EOD at least so you don't inject a ton of androgens at once and experience worse sides
Trenbolone Hexahydrolbenzoylcarbonate
Between the two other esters with a half life of approximately 8 days, nobody runs this ester due to it not being pharmaceutically produced anymore
Conclusion
Hopefully you learned something and truly imagine the CNS destruction of tren but also the high ROI when managed correctly
Trenbolone is a synthetic steroid not naturally occurring in humans, it is a 19 nor steroid derived from nandrolone. The chemical structure of trenbolone is unique, possessing a non-present carbon 19 atom and 3 double bonds located at carbons 4, 9, and 11. These properties in the chemical structure is what causes trenbolone to exhibit its high affinity to the AR, specifically the removal of the carbon 19 methyl group. The three double bonds on tren’s steroid core makes the molecule very rigid, combining this with the fact that it is a 19 nor meaning the C19 methyl group is missing makes it not a substrate for the aromatase enzyme. This triene shape also makes it resistant to 5 alpha reductase; this is because the electrons are delocalized across the conjugated double bonds, this helps the C4 double bond in the A ring resist 5AR thus yielding no DHT.
Tren obviously is much more potent than testosterone and has a higher binding affinity to the AR, like i said earlier this is because of the C19 not being present in tren’s molecule along with the triene structure. Tren has a similar binding affinity to dihydrotestosterone. Trenblone also has a slower dissociation rate from the androgen receptor which prolongs the receptor activation which enhances androgenic signaling. Trenbolone goes through genomic and non genomic pathways. Obviously the genomic pathway goes as follows: trenbolone enters the cytoplasm of a cell then binds to the ligand binding domain of the androgen receptor. The androgen receptor dissociates from chaperone proteins, dimerizes then translocates to the nucleus. Here it binds to AREs, recruits coactivators then alters the gene transcription and pumps out a biological effect. It's all simple stuff because tren is an androgen and goes through a lot of the same pathways endogenous androgens would go through. Tren also exerts its classical AR signaling at low concentrations so you don't need a lot of tren to get results.
On the topic of genomic signalling, Tren’s unique effects on the AR come from its chemical structure. This is obvious but when an androgen binds to the ligand binding domain of the AR it changes shape and recruits co activators through the formation of AF2. This is a hydrophobic groove in the receptor that allows for coactivator proteins to bind via amino acid sequences which help activate androgenic signaling. The AR also interacts with its own AF2 via the N terminal domain binding to the AF2 that can stabilize the AR and allow for longer signaling. Ligands change the receptor shape once bound to the receptors so tren could theoretically alter the AF2 more favorably compared to other androgens. Tren’s chemical structure could potentially alter the AF2 because once an androgen is in the LBD, helix 12 keeps it inside like a door, this is where the AF2 is formed. Tren could potentially make a better geometric place in the AF2 for coactivators and N terminal domain binding. Given tren’s strong androgenic signaling and enhanced effects this is very well the case.
Obviously being an androgen it can bind to mARs and activate downstream kinase cascades that are associated with muscle protein synthesis such as PI3K/akt/mTOR and MAPK/ERK. It also stabilizes β catenin which then helps with follistatin production which can antagonize myostatin on top of the androgen inhibiting myostatin directly by binding to the AR. Also PI3K/akt activation will of course inhibit foxO which will then drop production of degrading proteins such as MuRF and atrogin 1. The local IGF1 made from tren will also lead down into mTOR via the IGF1R. I'd recommend combining tren with something like oxymetholone so that the trenbolone occupies genomic AR signalling and the oxymetholone can handle non genomic signaling.
The fact that it doesn't aromatise makes you have nice dry gains. This is another reason why tren is the mogger cutting steroid that it is, along with GR antagonism and nutrient partitioning. Another cool thing about tren is that it may bind to the mineralocorticoid receptor, this of course helps with bloat as it antagonizes aldosterone. This may be a potential benefit because as we know tren has affinity to progesterone and glucocorticoid receptors and the mineralocorticoid receptor is in the same receptor family as those two and the AR. It's not crazy to assume that tren has an antagonist effect on the MR. Especially when this was observed in vitro upon taking tren’s cytotoxicity limit of 2.29 µM and finding activity for the mineralocorticoid receptor at concentrations lower than that, implying that its actual trenbolone activity rather than cell damage.
Tren has a low binding affinity to SHBG this allows way more of the hormone to be free and bind to ARs in target cells. This is why you always want to stay on the lower end of dosing when using tren, the number may look small but due to this property it's doing a lot more than you might think just looking at the dosing number.
Trenbolone enhances wnt pathway signalling via upregulation of β catenin and inhibition of notch pathways which antagonize wnt. This is obviously important as wnt is a growth pathway that is present in muscle and bone.
Tren enters myocyte/mesenchymal precursor cell → tren exerts negative effects on GSK3 and upregulates Numb via Tcf2/Lef gene transcription → more β catenin to exert his effects via wnt pathway and notch inhibition for further wnt signaling → muscle anabolism and mesenchymal precursor cells going down myogenesis lineage
In vivo it was shown to enhance this pathway using fish fins. Studies have observed this enhancement in myoblasts but we can also attribute this same mechanism to osteoblasts.
Trenbolone binds AR → more wnt ligand is created → wnt binds to frizzled receptors thus stabilizing β catenin → β catenin levels were raised because of trenbolones negative effects on GSK3 → more β catenin to bind with tren/AR complex as co activators → translocation to nucleus → osteogenetic gene transcription such as runx2 and osterix
Further adding on this, wnt upregulates OPG via TCF/LEC/tnfrsf11b gene transcription which further prevents resorption
Speaking of trenbolone acting on bone, it was shown that in studies using rats who were skeletally mature and who were orchiectomized that trenbolone partially or completely countered the bone loss from hypogonadism and maintained bone strength, enhancing the femoral neck in the rats. It's also good to note that in the presence of AIs the BMD caused from tren didn't get messed up at all which means that trenbolone doesn't need to aromatase into e2 to exert its effects on bone
In a study done on ORX rats testosterone and trenbolone were administered in the presence of anastrozole. The osteoclast surface was reduced in both groups however AI administration with test reduced the osteoclast surface reducing effects of test to that of SHAMs, while AI coadministration with tren resulted in zero reduction in trens osteoclast surface reducing effects. Maximum breaking loads of the femoral neck exceeded SHAMs in ORX + tren rats and was comparable to SHAMs in ORX + tren + AI rats. LABC mass was also greater in rats treated with tren compared to SHAMs, roughly 38-42% greater.
In the same study TE and tren also reduced the osteoblast surfaces in the bone that were caused from a high turnover rate due to ORX. This shows that the androgens reduced the turnover rate in hypogonadal rats and like the first statement, AI administration didn't change reduce trens effects
Gluticorticoid Receptor Antagonist
This is why tren mogs so hard while cutting, it just blocks the catabolic effects of cortisol. Tren decreases the amount of GR mRNA and also binds to the GR further antagonizing cortisol
The anti catabolic effects are not only in muscle as they are expressed in bone. GRs inhabit bone cells and cortisol can bind with them and increase sclerostin secretion and disrupt the OPG/RANKL axis and inhibits the wnt pathway which ultimately leads to osteoclastogenesis and bone resorption. Once tren enters this whole cascade just gets antagonized
IGF-1
Trenbolone makes you more sensitive to IGF1, in rat satellite cells it was shown that rats treated with tren had way more proliferation. In contrast it was shown that if you place tren directly in the medium of cultured satellite cells it did not have any proliferative effects. Comparing this with satellite cells from rats treated with tren who had greater proliferative effects to FGF and IGF1 clearly showing an increased sensitivity. So on top of potent paracrine IGF1 signalling, it contributes to increased systemic IGF1.
IGF1 also contributes to bone via IGF1R/akt+PI3K/mTOR activation which leads to the proliferation of osteblasts
Nutritional Parting
This refers to how much of your nutrients/calories goes to muscle or fat. Trenbolone has insane nutrient partitioning properties that make it so you can eat in a surplus and hardly gain any fat at all as it overwhelming goes to muscle tissue
This is caused by the increase of nitrogen retention in muscle tissues which drives better intake of nutrients to muscle. Tren also has positive effects on lipolysis so therefore there's not gonna be as much nutrients being stored as fat. Tren also improves glycogen stores in muscles which naturally makes you recover faster.
For an example let's say before tren 60% of your nutrients went to fat and 40% of it went to muscle, while on tren 70% will go to muscle while 30% will go to fat.
Side Effects
Gyno
Tren's strong affinity for the PR increases prolactin which can cause gyno
Neurotoxicity
Tren is neurotoxic. It can shorten neurites and cause neuron apoptosis. Tren accumulates a lot in your hippocampus, causing hippocampal neuron death and raising Aβ42 and caspase 3 levels essentially degrading your brain through the same pathways as alzheimer's disease. Along with that it also disrupts presenilin 1 and this is where it can mess with APP peptide production which leads to the upregulation of Aβ42 like we stated earlier.
Tren accumulates in hippocampus → decreases presenilin 1 and upregulates Aβ42 and caspase 3 activity → neurodegeneration/neuron apoptosis
Going along with AD like symptoms we have the fact that tren exacerbates TNF-α and IL1β inflammation which leads to activation of the hepatic IL6 inflammatory pathway which enhances release of LCN2 which then comes into the brain and expresses itself in the mPFC. This neurovisceral circuit eventually leads to the deposition of Aβ proteins which as you know is the pathway of which AD takes its toll.
Tren exacerbates TNF-α and IL1β → triggers hepatic IL6 inflammatory pathway → enhanced secretion of LCN2 which expresses itself in the brain → Aβ deposition → neurodegeneration
Tren increases neuroinflammation such as NLRP3 inflammasome, IL-6, IL-1α, and IL-1β as well as increasing proapoptotic proteins like caspase 3/7 and Bax while lowering anti apoptotic proteins such as DJ-1 and Bcl-1
Tren enters CNS → NLRP3 IL6 IL-1α IL-1β caspase 3/7 Bax increase Bcl-1 and DJ-1 decrease, tyrosine hydrolase reduction → domaminergic neuronal death worsening/neuronal apoptosis/dopamine pathway damage/substantia nigra damage
Tren causes declined mitochondrial function and causes lactate dehydrogenase release. This release is a marker of membrane damage and cell death. This mitochondrial decline comes from the neuroinflammatory cytokines I listed above, inhibition of neuroprotective proteins, as well as AR mediated pathways and oxidative stress.
Trensomnia is an effect you've heard thrown around if you know anything about tren, this is caused from an upregulation of orexin signaling which promotes wakefulness. Tren also disturbs motoneuron development and locomotion.
Tren enters CNS → upregulates orexin signaling → insomnia phenotype
I don't really know where to put this so fuck it, the thyroid is close enough to the brain. Tren suppresses t4 → t3 conversion
Tren creates a ton of ROS via an upregulation of nox, specifically hydroxyl radicals, the most destructive free radical, thus throwing off the balance of oxidants and antioxidants which then leads to oxidative stress.
Mental Side Effects
Tren can make you aggressive, this mechanism acts on NMDARs. Tren reduces these receptors in your hippocampus as well as your hypothalamus.
Anxiety is also a possibility on tren, the proposed mechanism is altering of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex. This can disrupt cortical glutamate making it increase and cause excitotoxicity and localized hypo reactivity which is linked to anxiety and social avoidance
Trenbolone suppresses endogenous testosterone and disturbs the TACR3 pathway in the hippocampus and thus inducing abnormal synaptic transmission signaling in the hippocampus, down regulation of synaptic proteins: PSD95, syn, gephyrin as well as metabolic imbalance in glutamate/GABA signaling. However having a test base will alleviate this, as observed in the rat study
Tren crosses BBB → down regulation of PSD95, syn, gephyrin, GABA/glutamate metabolic imbalance, down regulation of TACR3 hippocampus pathway → impaired synaptic plasticity and emotion regulation → anxiety behavior
Tren crosses BBB and disrupts maturation of oligodendrocytes → increase in glutamate and disruption of formation of the myelin sheath → excitotoxicity in the mPFC → anxiety
Trenbolone causes GABAergic disinhibition, tren can bind with GABAa receptors and make them go under allosteric modulation, modification of neuronal transmission and the activation and sensitivity of these receptors. As we know GABA is the inhibitory signals in your brain that calms your CNS, tren can basically change the way these receptors work to make you lower inhib and more aggressive
Tren crosses BBB → binds to GABAa receptors in the CNS → allosteric modulation of GABAa receptors → lower inhib/less inhibitory signals in CNS → impulsive behavior
Trenbolone of course suppresses the HPG axis and in a mice study this was found to disrupt sex steroids of course, altering AR and ERa levels in the testis. Tren also caused more dominant social behavior and stronger sexual attraction to females as well as males, when they checked for markers all they could find was increased c-Nos in the mPFC and the BLA.
Tren suppresses HPG axis → abnormal AR and ERa levels → disrupted sex steroid signaling → signaling in mPFC and BLA → social dominance and gayness
Proposed mechanism of course, but this could be how tren makes you gay.
19 nors cause shifts in density of serotonergic receptors in multiple regions in the brain, downregulation of 5HT1B receptor density in the hippocampus and in the medial globus pallidas. Upregulation of 5HT2 receptor density in the nucleus accumbens. Shifts in serotonergic receptors were also seen in more regions of the brain
By down regulating the 5HT1B it makes your serotonin brake not function properly and unable to inhibit impulsive behaviors, while this is happening an upregulation of 5HT2 makes it so that your reward system is hypersensitive making neutral things seem threatening and intense
Tren crosses BBB → up and down regulation of 5HT2 and 5HT1B serotonin receptors in multiple regions of the brain → Decreased impulse control and aggressive behavior
Tren isn't limited to mice studies when observing aggression, there have been studies that survey AAS users and have found a dose dependent relationship between trenbolone and verbal aggression
“After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression.”
“Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues.”
Tren not being to aromatase means there is pure androgenic signalling on your cardiovascular system without the added benefit of estrogen NO release and estrogen driven nephroprotectin. This results in high blood pressure which can also cause kidney problems. Although high creatinine is an issue, it doesn't really do much here as 19 nor cycles are relatively short.
Because estrogen cannot be provided from the trenbolone ligand, the androgenic effects on lipids is severe. Tren wrecks HDL while also raising LDL. This can lead to your arteries getting clogged and increasing workload on your cardiovascular system which therefore will lead to LVH.
Hematocrit will rise while on androgens and your blood will get thick, this is an issue because of clotting and more strain on the cardiovascular system.
Tren signals the adrenergic system which causes an overactive SNS which can narrow blood vessels forcing your heart to pump faster which leads to fast resting heart rate.
Tren also has hepatotoxic effects which in case reports was seen with severe transaminasemia which is a marker for AST/ALT enzymes in the bloodstream indicating hepatocyte injury. Also having hyperbilirubinemia caused by disrupted bile flow and also renal damage.
Liver markers showed cholestasis, sinusoidal dilation and cholangitis like changes, all are markers of hepatocyte injury and cholestatic injury.
All in all, trenbolone effects on the liver can be caused from oxidative stress, impaired bile export and disrupted hepatocyte transporter activity.
Memantine is an uncompetitive NMDA receptor antagonist that antagonizes glutamate which helps against neurodegeneration trenbolone will cause from glutamate excitotoxicity
Cerebrolysin - One Course Post Cycle
Peptide derived from pig brain with a low molecular weight allowing it to cross the BBB easily. Upregulates shh pathway to induce neural progenitor cell proliferation and oligodendrogenesis and neurogenesis. It mimics and stimulates neurotrophic growth factors in your brain like NTF3 and BDNF.
Cerebrolysin had been used for AD, traumatic brain injury and strokes with significantly beneficial results, should be able to cleave tren neurotoxicity adequately
Melatonin 100mg+
Sleep hormone that acts on MT1 and MT2 receptors to regulate circadian rhythm. At megadoses it can be a powerful antioxidant. It is a direct free radical scavenger and can neutralize a lot of ROS and RNS. It also stimulates a few antioxidant enzymes further pushing its antioxidant abilities.
Melatonin also binds to mt1 receptors on the mitochondrial membrane and dampening caspase activation through downstream pathways. Melatonin stimulates oxidative phosphorylation and promotes ATP production in neuronal and hepatocyte mitochondria.
Very mogger molecule that keeps cells safe from oxidative stress whilst also neutralizing ROS and RNS. One more thing about melatonin is that it inhibits NLRP3 inflammasome which is activated by tren and is linked to apoptosis
Propronal 10mg
Competitive nonselective beta blocker that acts on receptors β1 and β2 which can help reduce adrenaline and noradrenaline signaling and dampen the somatic feedback loop and its anxiety symptoms, thus reducing impulsive behavior and aggression and could potentially help with night sweats due to a relaxed SNS and suppressed somatic feedback loop
DORAs
Dual orexin receptor antagonists, targets both OX1R and OX2R to inhibit wakefulness signals of the orexin system that induce insomnia. No dependency issues arise either.
Empagliflozin 10mg
Increases mitochondria ATP production and reduces oxidative stress making the mitochondria more efficient
NACET 100mg
N-acetylcysteine with a longer half life and better bioavailability, is a precursor to glutathione which is your body's natural antioxidant. Crosses the BBB which allows for glutathione production in the CNS
9-Me-BC
Monoamine oxidase inhibitor that upregulates tyrosine hydrolase which can lead to dopaminergic synthesis. It also creates an anti inflammatory environment by decreasing inflammatory cytokines and receptors.
In studies it was shown to reverse the domaminergic neurotoxicity from MPP and make the dopaminergic immunoreactivity cells in the striata nigra go back to normal levels after exposed neurotoxicity.
Also reduces caspase 3 activity and increases ATP content and obviously dopaminergic neuron differentiation was increased
Astaxanthin
Carotenoid that has antioxidant benefits, crosses the BBB and suppresses the NF-κB pathway and also production of inflammatory cytokines. Linking to the membrane from inside to outside allows for better biological activity. Of course donates electrons to free radicals to neutralize them as well
Cardiovascular/Liver/Kidney protection
Telmisartan 160mg
Angiotensin 2 blocker that acts on angiotensin type 1 receptors to minimize vasoconstriction caused from overactive RAAS, also nice Insulin sensitivity bonus due to partial agonism of the PPARγ
Tadalafil 5-10mg
PDE5 Inhibitor that blocks the PDE5 enzyme from breaking down cGMP which lets smooth muscle relax and blood flow commence easier
Nebivolol 5-10mg
Highly selective β1 receptor antagonist that antagonizes adrenergic signaling in the heart, therefore lowering resting heart rate. Also has antihypertensive properties due to being a β3 agonist which stimulates nitric oxide release and vasodilation
Eplerenone 50mg
Selective MR antagonist that antagonizes aldosterone, thus stopping aldosterone from inducing myocardial fibrosis
Tudca 500mg
Bile acid that helps maintain bile flow to avoid cholestasis and also supports hepatocytes from ER stress by folding proteins
NACET 100mg
Cysteine → glutathione conversion used for antioxidant and hepatoprotection
Empagliflozin 10mg
SGLT2 inhibitor that handles glucose as well as having kidney protective properties by reducing workload placed on the kidneys. Cardio protection benefits are also included
Rupatadine 10mg
Histamine antagonist with selective peripheral H1 receptor antagonist activity blocking the receptors of PAF. This helps for tren’s PAF inflammatory signalling, you can throw this into a lot of cycles with AAS due to the inflammation
Pentoxifylline 400mg
Phosphodiesterase inhibitor that makes blood less vicious and makes red blood cells more flexible via increase ethyrocyte ATP and cyclic nucleotide levels which allows blood to travel through narrow passages which will be helpful with raised hematocrit from tren
Pemafibrate 0.2mg
The superior fibrate that selectively binds to PPARa for serum triglyceride reduction as well as increasing HDL. Helps liver function and doesn't place strain on the kidneys and can be taken along side with statins due to low drug interactions
Lipids/Prolactin/Thyroid
Pitavastatin 2-4mg
HMG-CoA reductase Inhibitor which is the enzyme used by the liver to make cholesterol. This causes an inhibition of mevalonic acid which then upregulates LDL receptors in hepatocytes to make up for the inhibition. These extra receptors grab LDL from your blood stream which leads to LDL catabolism. Also increases and enhances HDL
Ezetimibe 10mg
NPC1L1 protein blocker that inhibits the reabsorption of cholesterol from the small intestine and inhibiting the amount of cholesterol hepatocytes can use, thus making your body use circulating cholesterol which can help with high cholesterol especially when paired with a statin
P5P 200mg
L-tyrosine → L-DOPA → dopamine is the pathway in which p5p enhances. P5P is the active coenzyme b6 and helps L-DOPA convert into dopamine and bind to d2 receptors in the hypothalamus which puts a brake on prolactin secretion when reaching the pituitary
Cabergolin 0.5 - 2.5mg
D2 agonist that binds to dopamine receptors in the anterior pituitary and puts a brake on prolactin secretion
T4 + T3
Inactive and active thyroid hormones that control metabolic rate among other things. Since your conversion will slow down we'll just supplement these. Make sure to taper off nearing the end of your cycle and that your natural production of these hormones have rebounded
Hair/Skin
Isotretinoin 10-40mg
Shrinks sebaceous glands and reduces sebum production for no acne
Topical Estriol
Nice addition to any skincare routine, acts on ERs in the skin to promote elastin synthesis and is especially nice when used with retinoids
ru58841/kx-826
Both topical anti androgens, works by competing for androgen receptors and binding them so androgens can't bind to the AR, essential for compounds that bypass 5 alpha reduction.
Although tren itself isn't that androgenic due to the methyl group removal, these are still a nice edition if you plan on running DHT derivatives on your cycle
Esters
Trenbolone Acetate
Fastest acting ester with a half life of approximately 1-2 days, This calls for ED or EOD injections
Trenbolone Enanthate
Longer acting ester with a half life of approximately 11 days, would still make injections EOD at least so you don't inject a ton of androgens at once and experience worse sides
Trenbolone Hexahydrolbenzoylcarbonate
Between the two other esters with a half life of approximately 8 days, nobody runs this ester due to it not being pharmaceutically produced anymore
Conclusion
Hopefully you learned something and truly imagine the CNS destruction of tren but also the high ROI when managed correctly
Trenbolone is a synthetic steroid not naturally occurring in humans, it is a 19 nor steroid derived from nandrolone. The chemical structure of trenbolone is unique, possessing a non-present carbon 19 atom and 3 double bonds located at carbons 4, 9, and 11. These properties in the chemical structure is what causes trenbolone to exhibit its high affinity to the AR, specifically the removal of the carbon 19 methyl group. The three double bonds on tren’s steroid core makes the molecule very rigid, combining this with the fact that it is a 19 nor meaning the C19 methyl group is missing makes it not a substrate for the aromatase enzyme. This triene shape also makes it resistant to 5 alpha reductase; this is because the electrons are delocalized across the conjugated double bonds, this helps the C4 double bond in the A ring resist 5AR thus yielding no DHT.
Tren obviously is much more potent than testosterone and has a higher binding affinity to the AR, like i said earlier this is because of the C19 not being present in tren’s molecule along with the triene structure. Tren has a similar binding affinity to dihydrotestosterone. Trenblone also has a slower dissociation rate from the androgen receptor which prolongs the receptor activation which enhances androgenic signaling. Trenbolone goes through genomic and non genomic pathways. Obviously the genomic pathway goes as follows: trenbolone enters the cytoplasm of a cell then binds to the ligand binding domain of the androgen receptor. The androgen receptor dissociates from chaperone proteins, dimerizes then translocates to the nucleus. Here it binds to AREs, recruits coactivators then alters the gene transcription and pumps out a biological effect. It's all simple stuff because tren is an androgen and goes through a lot of the same pathways endogenous androgens would go through. Tren also exerts its classical AR signaling at low concentrations so you don't need a lot of tren to get results.
On the topic of genomic signalling, Tren’s unique effects on the AR come from its chemical structure. This is obvious but when an androgen binds to the ligand binding domain of the AR it changes shape and recruits co activators through the formation of AF2. This is a hydrophobic groove in the receptor that allows for coactivator proteins to bind via amino acid sequences which help activate androgenic signaling. The AR also interacts with its own AF2 via the N terminal domain binding to the AF2 that can stabilize the AR and allow for longer signaling. Ligands change the receptor shape once bound to the receptors so tren could theoretically alter the AF2 more favorably compared to other androgens. Tren’s chemical structure could potentially alter the AF2 because once an androgen is in the LBD, helix 12 keeps it inside like a door, this is where the AF2 is formed. Tren could potentially make a better geometric place in the AF2 for coactivators and N terminal domain binding. Given tren’s strong androgenic signaling and enhanced effects this is very well the case.
Obviously being an androgen it can bind to mARs and activate downstream kinase cascades that are associated with muscle protein synthesis such as PI3K/akt/mTOR and MAPK/ERK. It also stabilizes β catenin which then helps with follistatin production which can antagonize myostatin on top of the androgen inhibiting myostatin directly by binding to the AR. Also PI3K/akt activation will of course inhibit foxO which will then drop production of degrading proteins such as MuRF and atrogin 1. The local IGF1 made from tren will also lead down into mTOR via the IGF1R. I'd recommend combining tren with something like oxymetholone so that the trenbolone occupies genomic AR signalling and the oxymetholone can handle non genomic signaling.
The fact that it doesn't aromatise makes you have nice dry gains. This is another reason why tren is the mogger cutting steroid that it is, along with GR antagonism and nutrient partitioning. Another cool thing about tren is that it may bind to the mineralocorticoid receptor, this of course helps with bloat as it antagonizes aldosterone. This may be a potential benefit because as we know tren has affinity to progesterone and glucocorticoid receptors and the mineralocorticoid receptor is in the same receptor family as those two and the AR. It's not crazy to assume that tren has an antagonist effect on the MR. Especially when this was observed in vitro upon taking tren’s cytotoxicity limit of 2.29 µM and finding activity for the mineralocorticoid receptor at concentrations lower than that, implying that its actual trenbolone activity rather than cell damage.
Tren has a low binding affinity to SHBG this allows way more of the hormone to be free and bind to ARs in target cells. This is why you always want to stay on the lower end of dosing when using tren, the number may look small but due to this property it's doing a lot more than you might think just looking at the dosing number.
Trenbolone enhances wnt pathway signalling via upregulation of β catenin and inhibition of notch pathways which antagonize wnt. This is obviously important as wnt is a growth pathway that is present in muscle and bone.
Tren enters myocyte/mesenchymal precursor cell → tren exerts negative effects on GSK3 and upregulates Numb via Tcf2/Lef gene transcription → more β catenin to exert his effects via wnt pathway and notch inhibition for further wnt signaling → muscle anabolism and mesenchymal precursor cells going down myogenesis lineage
In vivo it was shown to enhance this pathway using fish fins. Studies have observed this enhancement in myoblasts but we can also attribute this same mechanism to osteoblasts.
Trenbolone binds AR → more wnt ligand is created → wnt binds to frizzled receptors thus stabilizing β catenin → β catenin levels were raised because of trenbolones negative effects on GSK3 → more β catenin to bind with tren/AR complex as co activators → translocation to nucleus → osteogenetic gene transcription such as runx2 and osterix
Further adding on this, wnt upregulates OPG via TCF/LEC/tnfrsf11b gene transcription which further prevents resorption
Speaking of trenbolone acting on bone, it was shown that in studies using rats who were skeletally mature and who were orchiectomized that trenbolone partially or completely countered the bone loss from hypogonadism and maintained bone strength, enhancing the femoral neck in the rats. It's also good to note that in the presence of AIs the BMD caused from tren didn't get messed up at all which means that trenbolone doesn't need to aromatase into e2 to exert its effects on bone
In a study done on ORX rats testosterone and trenbolone were administered in the presence of anastrozole. The osteoclast surface was reduced in both groups however AI administration with test reduced the osteoclast surface reducing effects of test to that of SHAMs, while AI coadministration with tren resulted in zero reduction in trens osteoclast surface reducing effects. Maximum breaking loads of the femoral neck exceeded SHAMs in ORX + tren rats and was comparable to SHAMs in ORX + tren + AI rats. LABC mass was also greater in rats treated with tren compared to SHAMs, roughly 38-42% greater.
In the same study TE and tren also reduced the osteoblast surfaces in the bone that were caused from a high turnover rate due to ORX. This shows that the androgens reduced the turnover rate in hypogonadal rats and like the first statement, AI administration didn't change reduce trens effects
Gluticorticoid Receptor Antagonist
This is why tren mogs so hard while cutting, it just blocks the catabolic effects of cortisol. Tren decreases the amount of GR mRNA and also binds to the GR further antagonizing cortisol
The anti catabolic effects are not only in muscle as they are expressed in bone. GRs inhabit bone cells and cortisol can bind with them and increase sclerostin secretion and disrupt the OPG/RANKL axis and inhibits the wnt pathway which ultimately leads to osteoclastogenesis and bone resorption. Once tren enters this whole cascade just gets antagonized
IGF-1
Trenbolone makes you more sensitive to IGF1, in rat satellite cells it was shown that rats treated with tren had way more proliferation. In contrast it was shown that if you place tren directly in the medium of cultured satellite cells it did not have any proliferative effects. Comparing this with satellite cells from rats treated with tren who had greater proliferative effects to FGF and IGF1 clearly showing an increased sensitivity. So on top of potent paracrine IGF1 signalling, it contributes to increased systemic IGF1.
IGF1 also contributes to bone via IGF1R/akt+PI3K/mTOR activation which leads to the proliferation of osteblasts
Nutritional Parting
This refers to how much of your nutrients/calories goes to muscle or fat. Trenbolone has insane nutrient partitioning properties that make it so you can eat in a surplus and hardly gain any fat at all as it overwhelming goes to muscle tissue
This is caused by the increase of nitrogen retention in muscle tissues which drives better intake of nutrients to muscle. Tren also has positive effects on lipolysis so therefore there's not gonna be as much nutrients being stored as fat. Tren also improves glycogen stores in muscles which naturally makes you recover faster.
For an example let's say before tren 60% of your nutrients went to fat and 40% of it went to muscle, while on tren 70% will go to muscle while 30% will go to fat.
Side Effects
Gyno
Tren's strong affinity for the PR increases prolactin which can cause gyno
Neurotoxicity
Tren is neurotoxic. It can shorten neurites and cause neuron apoptosis. Tren accumulates a lot in your hippocampus, causing hippocampal neuron death and raising Aβ42 and caspase 3 levels essentially degrading your brain through the same pathways as alzheimer's disease. Along with that it also disrupts presenilin 1 and this is where it can mess with APP peptide production which leads to the upregulation of Aβ42 like we stated earlier.
Tren accumulates in hippocampus → decreases presenilin 1 and upregulates Aβ42 and caspase 3 activity → neurodegeneration/neuron apoptosis
Going along with AD like symptoms we have the fact that tren exacerbates TNF-α and IL1β inflammation which leads to activation of the hepatic IL6 inflammatory pathway which enhances release of LCN2 which then comes into the brain and expresses itself in the mPFC. This neurovisceral circuit eventually leads to the deposition of Aβ proteins which as you know is the pathway of which AD takes its toll.
Tren exacerbates TNF-α and IL1β → triggers hepatic IL6 inflammatory pathway → enhanced secretion of LCN2 which expresses itself in the brain → Aβ deposition → neurodegeneration
Tren increases neuroinflammation such as NLRP3 inflammasome, IL-6, IL-1α, and IL-1β as well as increasing proapoptotic proteins like caspase 3/7 and Bax while lowering anti apoptotic proteins such as DJ-1 and Bcl-1
Tren enters CNS → NLRP3 IL6 IL-1α IL-1β caspase 3/7 Bax increase Bcl-1 and DJ-1 decrease, tyrosine hydrolase reduction → domaminergic neuronal death worsening/neuronal apoptosis/dopamine pathway damage/substantia nigra damage
Tren causes declined mitochondrial function and causes lactate dehydrogenase release. This release is a marker of membrane damage and cell death. This mitochondrial decline comes from the neuroinflammatory cytokines I listed above, inhibition of neuroprotective proteins, as well as AR mediated pathways and oxidative stress.
Trensomnia is an effect you've heard thrown around if you know anything about tren, this is caused from an upregulation of orexin signaling which promotes wakefulness. Tren also disturbs motoneuron development and locomotion.
Tren enters CNS → upregulates orexin signaling → insomnia phenotype
I don't really know where to put this so fuck it, the thyroid is close enough to the brain. Tren suppresses t4 → t3 conversion
Tren creates a ton of ROS via an upregulation of nox, specifically hydroxyl radicals, the most destructive free radical, thus throwing off the balance of oxidants and antioxidants which then leads to oxidative stress.
Mental Side Effects
Tren can make you aggressive, this mechanism acts on NMDARs. Tren reduces these receptors in your hippocampus as well as your hypothalamus.
Anxiety is also a possibility on tren, the proposed mechanism is altering of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex. This can disrupt cortical glutamate making it increase and cause excitotoxicity and localized hypo reactivity which is linked to anxiety and social avoidance
Trenbolone suppresses endogenous testosterone and disturbs the TACR3 pathway in the hippocampus and thus inducing abnormal synaptic transmission signaling in the hippocampus, down regulation of synaptic proteins: PSD95, syn, gephyrin as well as metabolic imbalance in glutamate/GABA signaling. However having a test base will alleviate this, as observed in the rat study
Tren crosses BBB → down regulation of PSD95, syn, gephyrin, GABA/glutamate metabolic imbalance, down regulation of TACR3 hippocampus pathway → impaired synaptic plasticity and emotion regulation → anxiety behavior
Tren crosses BBB and disrupts maturation of oligodendrocytes → increase in glutamate and disruption of formation of the myelin sheath → excitotoxicity in the mPFC → anxiety
Trenbolone causes GABAergic disinhibition, tren can bind with GABAa receptors and make them go under allosteric modulation, modification of neuronal transmission and the activation and sensitivity of these receptors. As we know GABA is the inhibitory signals in your brain that calms your CNS, tren can basically change the way these receptors work to make you lower inhib and more aggressive
Tren crosses BBB → binds to GABAa receptors in the CNS → allosteric modulation of GABAa receptors → lower inhib/less inhibitory signals in CNS → impulsive behavior
Trenbolone of course suppresses the HPG axis and in a mice study this was found to disrupt sex steroids of course, altering AR and ERa levels in the testis. Tren also caused more dominant social behavior and stronger sexual attraction to females as well as males, when they checked for markers all they could find was increased c-Nos in the mPFC and the BLA.
Tren suppresses HPG axis → abnormal AR and ERa levels → disrupted sex steroid signaling → signaling in mPFC and BLA → social dominance and gayness
Proposed mechanism of course, but this could be how tren makes you gay.
19 nors cause shifts in density of serotonergic receptors in multiple regions in the brain, downregulation of 5HT1B receptor density in the hippocampus and in the medial globus pallidas. Upregulation of 5HT2 receptor density in the nucleus accumbens. Shifts in serotonergic receptors were also seen in more regions of the brain
By down regulating the 5HT1B it makes your serotonin brake not function properly and unable to inhibit impulsive behaviors, while this is happening an upregulation of 5HT2 makes it so that your reward system is hypersensitive making neutral things seem threatening and intense
Tren crosses BBB → up and down regulation of 5HT2 and 5HT1B serotonin receptors in multiple regions of the brain → Decreased impulse control and aggressive behavior
Tren isn't limited to mice studies when observing aggression, there have been studies that survey AAS users and have found a dose dependent relationship between trenbolone and verbal aggression
“After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression.”
“Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues.”
Tren not being to aromatase means there is pure androgenic signalling on your cardiovascular system without the added benefit of estrogen NO release and estrogen driven nephroprotectin. This results in high blood pressure which can also cause kidney problems. Although high creatinine is an issue, it doesn't really do much here as 19 nor cycles are relatively short.
Because estrogen cannot be provided from the trenbolone ligand, the androgenic effects on lipids is severe. Tren wrecks HDL while also raising LDL. This can lead to your arteries getting clogged and increasing workload on your cardiovascular system which therefore will lead to LVH.
Hematocrit will rise while on androgens and your blood will get thick, this is an issue because of clotting and more strain on the cardiovascular system.
Tren signals the adrenergic system which causes an overactive SNS which can narrow blood vessels forcing your heart to pump faster which leads to fast resting heart rate.
Tren also has hepatotoxic effects which in case reports was seen with severe transaminasemia which is a marker for AST/ALT enzymes in the bloodstream indicating hepatocyte injury. Also having hyperbilirubinemia caused by disrupted bile flow and also renal damage.
Liver markers showed cholestasis, sinusoidal dilation and cholangitis like changes, all are markers of hepatocyte injury and cholestatic injury.
All in all, trenbolone effects on the liver can be caused from oxidative stress, impaired bile export and disrupted hepatocyte transporter activity.
Memantine is an uncompetitive NMDA receptor antagonist that antagonizes glutamate which helps against neurodegeneration trenbolone will cause from glutamate excitotoxicity
Cerebrolysin - One Course Post Cycle
Peptide derived from pig brain with a low molecular weight allowing it to cross the BBB easily. Upregulates shh pathway to induce neural progenitor cell proliferation and oligodendrogenesis and neurogenesis. It mimics and stimulates neurotrophic growth factors in your brain like NTF3 and BDNF.
Cerebrolysin had been used for AD, traumatic brain injury and strokes with significantly beneficial results, should be able to cleave tren neurotoxicity adequately
Melatonin 100mg+
Sleep hormone that acts on MT1 and MT2 receptors to regulate circadian rhythm. At megadoses it can be a powerful antioxidant. It is a direct free radical scavenger and can neutralize a lot of ROS and RNS. It also stimulates a few antioxidant enzymes further pushing its antioxidant abilities.
Melatonin also binds to mt1 receptors on the mitochondrial membrane and dampening caspase activation through downstream pathways. Melatonin stimulates oxidative phosphorylation and promotes ATP production in neuronal and hepatocyte mitochondria.
Very mogger molecule that keeps cells safe from oxidative stress whilst also neutralizing ROS and RNS. One more thing about melatonin is that it inhibits NLRP3 inflammasome which is activated by tren and is linked to apoptosis
Propronal 10mg
Competitive nonselective beta blocker that acts on receptors β1 and β2 which can help reduce adrenaline and noradrenaline signaling and dampen the somatic feedback loop and its anxiety symptoms, thus reducing impulsive behavior and aggression and could potentially help with night sweats due to a relaxed SNS and suppressed somatic feedback loop
DORAs
Dual orexin receptor antagonists, targets both OX1R and OX2R to inhibit wakefulness signals of the orexin system that induce insomnia. No dependency issues arise either.
Empagliflozin 10mg
Increases mitochondria ATP production and reduces oxidative stress making the mitochondria more efficient
NACET 100mg
N-acetylcysteine with a longer half life and better bioavailability, is a precursor to glutathione which is your body's natural antioxidant. Crosses the BBB which allows for glutathione production in the CNS
9-Me-BC
Monoamine oxidase inhibitor that upregulates tyrosine hydrolase which can lead to dopaminergic synthesis. It also creates an anti inflammatory environment by decreasing inflammatory cytokines and receptors.
In studies it was shown to reverse the domaminergic neurotoxicity from MPP and make the dopaminergic immunoreactivity cells in the striata nigra go back to normal levels after exposed neurotoxicity.
Also reduces caspase 3 activity and increases ATP content and obviously dopaminergic neuron differentiation was increased
Astaxanthin
Carotenoid that has antioxidant benefits, crosses the BBB and suppresses the NF-κB pathway and also production of inflammatory cytokines. Linking to the membrane from inside to outside allows for better biological activity. Of course donates electrons to free radicals to neutralize them as well
Cardiovascular/Liver/Kidney protection
Telmisartan 160mg
Angiotensin 2 blocker that acts on angiotensin type 1 receptors to minimize vasoconstriction caused from overactive RAAS, also nice Insulin sensitivity bonus due to partial agonism of the PPARγ
Tadalafil 5-10mg
PDE5 Inhibitor that blocks the PDE5 enzyme from breaking down cGMP which lets smooth muscle relax and blood flow commence easier
Nebivolol 5-10mg
Highly selective β1 receptor antagonist that antagonizes adrenergic signaling in the heart, therefore lowering resting heart rate. Also has antihypertensive properties due to being a β3 agonist which stimulates nitric oxide release and vasodilation
Eplerenone 50mg
Selective MR antagonist that antagonizes aldosterone, thus stopping aldosterone from inducing myocardial fibrosis
Tudca 500mg
Bile acid that helps maintain bile flow to avoid cholestasis and also supports hepatocytes from ER stress by folding proteins
NACET 100mg
Cysteine → glutathione conversion used for antioxidant and hepatoprotection
Empagliflozin 10mg
SGLT2 inhibitor that handles glucose as well as having kidney protective properties by reducing workload placed on the kidneys. Cardio protection benefits are also included
Rupatadine 10mg
Histamine antagonist with selective peripheral H1 receptor antagonist activity blocking the receptors of PAF. This helps for tren’s PAF inflammatory signalling, you can throw this into a lot of cycles with AAS due to the inflammation
Pentoxifylline 400mg
Phosphodiesterase inhibitor that makes blood less vicious and makes red blood cells more flexible via increase ethyrocyte ATP and cyclic nucleotide levels which allows blood to travel through narrow passages which will be helpful with raised hematocrit from tren
Pemafibrate 0.2mg
The superior fibrate that selectively binds to PPARa for serum triglyceride reduction as well as increasing HDL. Helps liver function and doesn't place strain on the kidneys and can be taken along side with statins due to low drug interactions
Lipids/Prolactin/Thyroid
Pitavastatin 2-4mg
HMG-CoA reductase Inhibitor which is the enzyme used by the liver to make cholesterol. This causes an inhibition of mevalonic acid which then upregulates LDL receptors in hepatocytes to make up for the inhibition. These extra receptors grab LDL from your blood stream which leads to LDL catabolism. Also increases and enhances HDL
Ezetimibe 10mg
NPC1L1 protein blocker that inhibits the reabsorption of cholesterol from the small intestine and inhibiting the amount of cholesterol hepatocytes can use, thus making your body use circulating cholesterol which can help with high cholesterol especially when paired with a statin
P5P 200mg
L-tyrosine → L-DOPA → dopamine is the pathway in which p5p enhances. P5P is the active coenzyme b6 and helps L-DOPA convert into dopamine and bind to d2 receptors in the hypothalamus which puts a brake on prolactin secretion when reaching the pituitary
Cabergolin 0.5 - 2.5mg
D2 agonist that binds to dopamine receptors in the anterior pituitary and puts a brake on prolactin secretion
T4 + T3
Inactive and active thyroid hormones that control metabolic rate among other things. Since your conversion will slow down we'll just supplement these. Make sure to taper off nearing the end of your cycle and that your natural production of these hormones have rebounded
Hair/Skin
Isotretinoin 10-40mg
Shrinks sebaceous glands and reduces sebum production for no acne
Topical Estriol
Nice addition to any skincare routine, acts on ERs in the skin to promote elastin synthesis and is especially nice when used with retinoids
ru58841/kx-826
Both topical anti androgens, works by competing for androgen receptors and binding them so androgens can't bind to the AR, essential for compounds that bypass 5 alpha reduction.
Although tren itself isn't that androgenic due to the methyl group removal, these are still a nice edition if you plan on running DHT derivatives on your cycle
Esters
Trenbolone Acetate
Fastest acting ester with a half life of approximately 1-2 days, This calls for ED or EOD injections
Trenbolone Enanthate
Longer acting ester with a half life of approximately 11 days, would still make injections EOD at least so you don't inject a ton of androgens at once and experience worse sides
Trenbolone Hexahydrolbenzoylcarbonate
Between the two other esters with a half life of approximately 8 days, nobody runs this ester due to it not being pharmaceutically produced anymore
Conclusion
Hopefully you learned something and truly imagine the CNS destruction of tren but also the high ROI when managed correctly
Trenbolone is a synthetic steroid not naturally occurring in humans, it is a 19 nor steroid derived from nandrolone. The chemical structure of trenbolone is unique, possessing a non-present carbon 19 atom and 3 double bonds located at carbons 4, 9, and 11. These properties in the chemical structure is what causes trenbolone to exhibit its high affinity to the AR, specifically the removal of the carbon 19 methyl group. The three double bonds on tren’s steroid core makes the molecule very rigid, combining this with the fact that it is a 19 nor meaning the C19 methyl group is missing makes it not a substrate for the aromatase enzyme. This triene shape also makes it resistant to 5 alpha reductase; this is because the electrons are delocalized across the conjugated double bonds, this helps the C4 double bond in the A ring resist 5AR thus yielding no DHT.
Tren obviously is much more potent than testosterone and has a higher binding affinity to the AR, like i said earlier this is because of the C19 not being present in tren’s molecule along with the triene structure. Tren has a similar binding affinity to dihydrotestosterone. Trenblone also has a slower dissociation rate from the androgen receptor which prolongs the receptor activation which enhances androgenic signaling. Trenbolone goes through genomic and non genomic pathways. Obviously the genomic pathway goes as follows: trenbolone enters the cytoplasm of a cell then binds to the ligand binding domain of the androgen receptor. The androgen receptor dissociates from chaperone proteins, dimerizes then translocates to the nucleus. Here it binds to AREs, recruits coactivators then alters the gene transcription and pumps out a biological effect. It's all simple stuff because tren is an androgen and goes through a lot of the same pathways endogenous androgens would go through. Tren also exerts its classical AR signaling at low concentrations so you don't need a lot of tren to get results.
On the topic of genomic signalling, Tren’s unique effects on the AR come from its chemical structure. This is obvious but when an androgen binds to the ligand binding domain of the AR it changes shape and recruits co activators through the formation of AF2. This is a hydrophobic groove in the receptor that allows for coactivator proteins to bind via amino acid sequences which help activate androgenic signaling. The AR also interacts with its own AF2 via the N terminal domain binding to the AF2 that can stabilize the AR and allow for longer signaling. Ligands change the receptor shape once bound to the receptors so tren could theoretically alter the AF2 more favorably compared to other androgens. Tren’s chemical structure could potentially alter the AF2 because once an androgen is in the LBD, helix 12 keeps it inside like a door, this is where the AF2 is formed. Tren could potentially make a better geometric place in the AF2 for coactivators and N terminal domain binding. Given tren’s strong androgenic signaling and enhanced effects this is very well the case.
Obviously being an androgen it can bind to mARs and activate downstream kinase cascades that are associated with muscle protein synthesis such as PI3K/akt/mTOR and MAPK/ERK. It also stabilizes β catenin which then helps with follistatin production which can antagonize myostatin on top of the androgen inhibiting myostatin directly by binding to the AR. Also PI3K/akt activation will of course inhibit foxO which will then drop production of degrading proteins such as MuRF and atrogin 1. The local IGF1 made from tren will also lead down into mTOR via the IGF1R. I'd recommend combining tren with something like oxymetholone so that the trenbolone occupies genomic AR signalling and the oxymetholone can handle non genomic signaling.
The fact that it doesn't aromatise makes you have nice dry gains. This is another reason why tren is the mogger cutting steroid that it is, along with GR antagonism and nutrient partitioning. Another cool thing about tren is that it may bind to the mineralocorticoid receptor, this of course helps with bloat as it antagonizes aldosterone. This may be a potential benefit because as we know tren has affinity to progesterone and glucocorticoid receptors and the mineralocorticoid receptor is in the same receptor family as those two and the AR. It's not crazy to assume that tren has an antagonist effect on the MR. Especially when this was observed in vitro upon taking tren’s cytotoxicity limit of 2.29 µM and finding activity for the mineralocorticoid receptor at concentrations lower than that, implying that its actual trenbolone activity rather than cell damage.
Tren has a low binding affinity to SHBG this allows way more of the hormone to be free and bind to ARs in target cells. This is why you always want to stay on the lower end of dosing when using tren, the number may look small but due to this property it's doing a lot more than you might think just looking at the dosing number.
Trenbolone enhances wnt pathway signalling via upregulation of β catenin and inhibition of notch pathways which antagonize wnt. This is obviously important as wnt is a growth pathway that is present in muscle and bone.
Tren enters myocyte/mesenchymal precursor cell → tren exerts negative effects on GSK3 and upregulates Numb via Tcf2/Lef gene transcription → more β catenin to exert his effects via wnt pathway and notch inhibition for further wnt signaling → muscle anabolism and mesenchymal precursor cells going down myogenesis lineage
In vivo it was shown to enhance this pathway using fish fins. Studies have observed this enhancement in myoblasts but we can also attribute this same mechanism to osteoblasts.
Trenbolone binds AR → more wnt ligand is created → wnt binds to frizzled receptors thus stabilizing β catenin → β catenin levels were raised because of trenbolones negative effects on GSK3 → more β catenin to bind with tren/AR complex as co activators → translocation to nucleus → osteogenetic gene transcription such as runx2 and osterix
Further adding on this, wnt upregulates OPG via TCF/LEC/tnfrsf11b gene transcription which further prevents resorption
Speaking of trenbolone acting on bone, it was shown that in studies using rats who were skeletally mature and who were orchiectomized that trenbolone partially or completely countered the bone loss from hypogonadism and maintained bone strength, enhancing the femoral neck in the rats. It's also good to note that in the presence of AIs the BMD caused from tren didn't get messed up at all which means that trenbolone doesn't need to aromatase into e2 to exert its effects on bone
In a study done on ORX rats testosterone and trenbolone were administered in the presence of anastrozole. The osteoclast surface was reduced in both groups however AI administration with test reduced the osteoclast surface reducing effects of test to that of SHAMs, while AI coadministration with tren resulted in zero reduction in trens osteoclast surface reducing effects. Maximum breaking loads of the femoral neck exceeded SHAMs in ORX + tren rats and was comparable to SHAMs in ORX + tren + AI rats. LABC mass was also greater in rats treated with tren compared to SHAMs, roughly 38-42% greater.
In the same study TE and tren also reduced the osteoblast surfaces in the bone that were caused from a high turnover rate due to ORX. This shows that the androgens reduced the turnover rate in hypogonadal rats and like the first statement, AI administration didn't change reduce trens effects
Gluticorticoid Receptor Antagonist
This is why tren mogs so hard while cutting, it just blocks the catabolic effects of cortisol. Tren decreases the amount of GR mRNA and also binds to the GR further antagonizing cortisol
The anti catabolic effects are not only in muscle as they are expressed in bone. GRs inhabit bone cells and cortisol can bind with them and increase sclerostin secretion and disrupt the OPG/RANKL axis and inhibits the wnt pathway which ultimately leads to osteoclastogenesis and bone resorption. Once tren enters this whole cascade just gets antagonized
IGF-1
Trenbolone makes you more sensitive to IGF1, in rat satellite cells it was shown that rats treated with tren had way more proliferation. In contrast it was shown that if you place tren directly in the medium of cultured satellite cells it did not have any proliferative effects. Comparing this with satellite cells from rats treated with tren who had greater proliferative effects to FGF and IGF1 clearly showing an increased sensitivity. So on top of potent paracrine IGF1 signalling, it contributes to increased systemic IGF1.
IGF1 also contributes to bone via IGF1R/akt+PI3K/mTOR activation which leads to the proliferation of osteblasts
Nutritional Parting
This refers to how much of your nutrients/calories goes to muscle or fat. Trenbolone has insane nutrient partitioning properties that make it so you can eat in a surplus and hardly gain any fat at all as it overwhelming goes to muscle tissue
This is caused by the increase of nitrogen retention in muscle tissues which drives better intake of nutrients to muscle. Tren also has positive effects on lipolysis so therefore there's not gonna be as much nutrients being stored as fat. Tren also improves glycogen stores in muscles which naturally makes you recover faster.
For an example let's say before tren 60% of your nutrients went to fat and 40% of it went to muscle, while on tren 70% will go to muscle while 30% will go to fat.
Side Effects
Gyno
Tren's strong affinity for the PR increases prolactin which can cause gyno
Neurotoxicity
Tren is neurotoxic. It can shorten neurites and cause neuron apoptosis. Tren accumulates a lot in your hippocampus, causing hippocampal neuron death and raising Aβ42 and caspase 3 levels essentially degrading your brain through the same pathways as alzheimer's disease. Along with that it also disrupts presenilin 1 and this is where it can mess with APP peptide production which leads to the upregulation of Aβ42 like we stated earlier.
Tren accumulates in hippocampus → decreases presenilin 1 and upregulates Aβ42 and caspase 3 activity → neurodegeneration/neuron apoptosis
Going along with AD like symptoms we have the fact that tren exacerbates TNF-α and IL1β inflammation which leads to activation of the hepatic IL6 inflammatory pathway which enhances release of LCN2 which then comes into the brain and expresses itself in the mPFC. This neurovisceral circuit eventually leads to the deposition of Aβ proteins which as you know is the pathway of which AD takes its toll.
Tren exacerbates TNF-α and IL1β → triggers hepatic IL6 inflammatory pathway → enhanced secretion of LCN2 which expresses itself in the brain → Aβ deposition → neurodegeneration
Tren increases neuroinflammation such as NLRP3 inflammasome, IL-6, IL-1α, and IL-1β as well as increasing proapoptotic proteins like caspase 3/7 and Bax while lowering anti apoptotic proteins such as DJ-1 and Bcl-1
Tren enters CNS → NLRP3 IL6 IL-1α IL-1β caspase 3/7 Bax increase Bcl-1 and DJ-1 decrease, tyrosine hydrolase reduction → domaminergic neuronal death worsening/neuronal apoptosis/dopamine pathway damage/substantia nigra damage
Tren causes declined mitochondrial function and causes lactate dehydrogenase release. This release is a marker of membrane damage and cell death. This mitochondrial decline comes from the neuroinflammatory cytokines I listed above, inhibition of neuroprotective proteins, as well as AR mediated pathways and oxidative stress.
Trensomnia is an effect you've heard thrown around if you know anything about tren, this is caused from an upregulation of orexin signaling which promotes wakefulness. Tren also disturbs motoneuron development and locomotion.
Tren enters CNS → upregulates orexin signaling → insomnia phenotype
I don't really know where to put this so fuck it, the thyroid is close enough to the brain. Tren suppresses t4 → t3 conversion
Tren creates a ton of ROS via an upregulation of nox, specifically hydroxyl radicals, the most destructive free radical, thus throwing off the balance of oxidants and antioxidants which then leads to oxidative stress.
Mental Side Effects
Tren can make you aggressive, this mechanism acts on NMDARs. Tren reduces these receptors in your hippocampus as well as your hypothalamus.
Anxiety is also a possibility on tren, the proposed mechanism is altering of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex. This can disrupt cortical glutamate making it increase and cause excitotoxicity and localized hypo reactivity which is linked to anxiety and social avoidance
Trenbolone suppresses endogenous testosterone and disturbs the TACR3 pathway in the hippocampus and thus inducing abnormal synaptic transmission signaling in the hippocampus, down regulation of synaptic proteins: PSD95, syn, gephyrin as well as metabolic imbalance in glutamate/GABA signaling. However having a test base will alleviate this, as observed in the rat study
Tren crosses BBB → down regulation of PSD95, syn, gephyrin, GABA/glutamate metabolic imbalance, down regulation of TACR3 hippocampus pathway → impaired synaptic plasticity and emotion regulation → anxiety behavior
Tren crosses BBB and disrupts maturation of oligodendrocytes → increase in glutamate and disruption of formation of the myelin sheath → excitotoxicity in the mPFC → anxiety
Trenbolone causes GABAergic disinhibition, tren can bind with GABAa receptors and make them go under allosteric modulation, modification of neuronal transmission and the activation and sensitivity of these receptors. As we know GABA is the inhibitory signals in your brain that calms your CNS, tren can basically change the way these receptors work to make you lower inhib and more aggressive
Tren crosses BBB → binds to GABAa receptors in the CNS → allosteric modulation of GABAa receptors → lower inhib/less inhibitory signals in CNS → impulsive behavior
Trenbolone of course suppresses the HPG axis and in a mice study this was found to disrupt sex steroids of course, altering AR and ERa levels in the testis. Tren also caused more dominant social behavior and stronger sexual attraction to females as well as males, when they checked for markers all they could find was increased c-Nos in the mPFC and the BLA.
Tren suppresses HPG axis → abnormal AR and ERa levels → disrupted sex steroid signaling → signaling in mPFC and BLA → social dominance and gayness
Proposed mechanism of course, but this could be how tren makes you gay.
19 nors cause shifts in density of serotonergic receptors in multiple regions in the brain, downregulation of 5HT1B receptor density in the hippocampus and in the medial globus pallidas. Upregulation of 5HT2 receptor density in the nucleus accumbens. Shifts in serotonergic receptors were also seen in more regions of the brain
By down regulating the 5HT1B it makes your serotonin brake not function properly and unable to inhibit impulsive behaviors, while this is happening an upregulation of 5HT2 makes it so that your reward system is hypersensitive making neutral things seem threatening and intense
Tren crosses BBB → up and down regulation of 5HT2 and 5HT1B serotonin receptors in multiple regions of the brain → Decreased impulse control and aggressive behavior
Tren isn't limited to mice studies when observing aggression, there have been studies that survey AAS users and have found a dose dependent relationship between trenbolone and verbal aggression
“After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression.”
“Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues.”
Tren not being to aromatase means there is pure androgenic signalling on your cardiovascular system without the added benefit of estrogen NO release and estrogen driven nephroprotectin. This results in high blood pressure which can also cause kidney problems. Although high creatinine is an issue, it doesn't really do much here as 19 nor cycles are relatively short.
Because estrogen cannot be provided from the trenbolone ligand, the androgenic effects on lipids is severe. Tren wrecks HDL while also raising LDL. This can lead to your arteries getting clogged and increasing workload on your cardiovascular system which therefore will lead to LVH.
Hematocrit will rise while on androgens and your blood will get thick, this is an issue because of clotting and more strain on the cardiovascular system.
Tren signals the adrenergic system which causes an overactive SNS which can narrow blood vessels forcing your heart to pump faster which leads to fast resting heart rate.
Tren also has hepatotoxic effects which in case reports was seen with severe transaminasemia which is a marker for AST/ALT enzymes in the bloodstream indicating hepatocyte injury. Also having hyperbilirubinemia caused by disrupted bile flow and also renal damage.
Liver markers showed cholestasis, sinusoidal dilation and cholangitis like changes, all are markers of hepatocyte injury and cholestatic injury.
All in all, trenbolone effects on the liver can be caused from oxidative stress, impaired bile export and disrupted hepatocyte transporter activity.
Memantine is an uncompetitive NMDA receptor antagonist that antagonizes glutamate which helps against neurodegeneration trenbolone will cause from glutamate excitotoxicity
Cerebrolysin - One Course Post Cycle
Peptide derived from pig brain with a low molecular weight allowing it to cross the BBB easily. Upregulates shh pathway to induce neural progenitor cell proliferation and oligodendrogenesis and neurogenesis. It mimics and stimulates neurotrophic growth factors in your brain like NTF3 and BDNF.
Cerebrolysin had been used for AD, traumatic brain injury and strokes with significantly beneficial results, should be able to cleave tren neurotoxicity adequately
Melatonin 100mg+
Sleep hormone that acts on MT1 and MT2 receptors to regulate circadian rhythm. At megadoses it can be a powerful antioxidant. It is a direct free radical scavenger and can neutralize a lot of ROS and RNS. It also stimulates a few antioxidant enzymes further pushing its antioxidant abilities.
Melatonin also binds to mt1 receptors on the mitochondrial membrane and dampening caspase activation through downstream pathways. Melatonin stimulates oxidative phosphorylation and promotes ATP production in neuronal and hepatocyte mitochondria.
Very mogger molecule that keeps cells safe from oxidative stress whilst also neutralizing ROS and RNS. One more thing about melatonin is that it inhibits NLRP3 inflammasome which is activated by tren and is linked to apoptosis
Propronal 10mg
Competitive nonselective beta blocker that acts on receptors β1 and β2 which can help reduce adrenaline and noradrenaline signaling and dampen the somatic feedback loop and its anxiety symptoms, thus reducing impulsive behavior and aggression and could potentially help with night sweats due to a relaxed SNS and suppressed somatic feedback loop
DORAs
Dual orexin receptor antagonists, targets both OX1R and OX2R to inhibit wakefulness signals of the orexin system that induce insomnia. No dependency issues arise either.
Empagliflozin 10mg
Increases mitochondria ATP production and reduces oxidative stress making the mitochondria more efficient
NACET 100mg
N-acetylcysteine with a longer half life and better bioavailability, is a precursor to glutathione which is your body's natural antioxidant. Crosses the BBB which allows for glutathione production in the CNS
9-Me-BC
Monoamine oxidase inhibitor that upregulates tyrosine hydrolase which can lead to dopaminergic synthesis. It also creates an anti inflammatory environment by decreasing inflammatory cytokines and receptors.
In studies it was shown to reverse the domaminergic neurotoxicity from MPP and make the dopaminergic immunoreactivity cells in the striata nigra go back to normal levels after exposed neurotoxicity.
Also reduces caspase 3 activity and increases ATP content and obviously dopaminergic neuron differentiation was increased
Astaxanthin
Carotenoid that has antioxidant benefits, crosses the BBB and suppresses the NF-κB pathway and also production of inflammatory cytokines. Linking to the membrane from inside to outside allows for better biological activity. Of course donates electrons to free radicals to neutralize them as well
Cardiovascular/Liver/Kidney protection
Telmisartan 160mg
Angiotensin 2 blocker that acts on angiotensin type 1 receptors to minimize vasoconstriction caused from overactive RAAS, also nice Insulin sensitivity bonus due to partial agonism of the PPARγ
Tadalafil 5-10mg
PDE5 Inhibitor that blocks the PDE5 enzyme from breaking down cGMP which lets smooth muscle relax and blood flow commence easier
Nebivolol 5-10mg
Highly selective β1 receptor antagonist that antagonizes adrenergic signaling in the heart, therefore lowering resting heart rate. Also has antihypertensive properties due to being a β3 agonist which stimulates nitric oxide release and vasodilation
Eplerenone 50mg
Selective MR antagonist that antagonizes aldosterone, thus stopping aldosterone from inducing myocardial fibrosis
Tudca 500mg
Bile acid that helps maintain bile flow to avoid cholestasis and also supports hepatocytes from ER stress by folding proteins
NACET 100mg
Cysteine → glutathione conversion used for antioxidant and hepatoprotection
Empagliflozin 10mg
SGLT2 inhibitor that handles glucose as well as having kidney protective properties by reducing workload placed on the kidneys. Cardio protection benefits are also included
Rupatadine 10mg
Histamine antagonist with selective peripheral H1 receptor antagonist activity blocking the receptors of PAF. This helps for tren’s PAF inflammatory signalling, you can throw this into a lot of cycles with AAS due to the inflammation
Pentoxifylline 400mg
Phosphodiesterase inhibitor that makes blood less vicious and makes red blood cells more flexible via increase ethyrocyte ATP and cyclic nucleotide levels which allows blood to travel through narrow passages which will be helpful with raised hematocrit from tren
Pemafibrate 0.2mg
The superior fibrate that selectively binds to PPARa for serum triglyceride reduction as well as increasing HDL. Helps liver function and doesn't place strain on the kidneys and can be taken along side with statins due to low drug interactions
Lipids/Prolactin/Thyroid
Pitavastatin 2-4mg
HMG-CoA reductase Inhibitor which is the enzyme used by the liver to make cholesterol. This causes an inhibition of mevalonic acid which then upregulates LDL receptors in hepatocytes to make up for the inhibition. These extra receptors grab LDL from your blood stream which leads to LDL catabolism. Also increases and enhances HDL
Ezetimibe 10mg
NPC1L1 protein blocker that inhibits the reabsorption of cholesterol from the small intestine and inhibiting the amount of cholesterol hepatocytes can use, thus making your body use circulating cholesterol which can help with high cholesterol especially when paired with a statin
P5P 200mg
L-tyrosine → L-DOPA → dopamine is the pathway in which p5p enhances. P5P is the active coenzyme b6 and helps L-DOPA convert into dopamine and bind to d2 receptors in the hypothalamus which puts a brake on prolactin secretion when reaching the pituitary
Cabergolin 0.5 - 2.5mg
D2 agonist that binds to dopamine receptors in the anterior pituitary and puts a brake on prolactin secretion
T4 + T3
Inactive and active thyroid hormones that control metabolic rate among other things. Since your conversion will slow down we'll just supplement these. Make sure to taper off nearing the end of your cycle and that your natural production of these hormones have rebounded
Hair/Skin
Isotretinoin 10-40mg
Shrinks sebaceous glands and reduces sebum production for no acne
Topical Estriol
Nice addition to any skincare routine, acts on ERs in the skin to promote elastin synthesis and is especially nice when used with retinoids
ru58841/kx-826
Both topical anti androgens, works by competing for androgen receptors and binding them so androgens can't bind to the AR, essential for compounds that bypass 5 alpha reduction.
Although tren itself isn't that androgenic due to the methyl group removal, these are still a nice edition if you plan on running DHT derivatives on your cycle
Esters
Trenbolone Acetate
Fastest acting ester with a half life of approximately 1-2 days, This calls for ED or EOD injections
Trenbolone Enanthate
Longer acting ester with a half life of approximately 11 days, would still make injections EOD at least so you don't inject a ton of androgens at once and experience worse sides
Trenbolone Hexahydrolbenzoylcarbonate
Between the two other esters with a half life of approximately 8 days, nobody runs this ester due to it not being pharmaceutically produced anymore
Conclusion
Hopefully you learned something and truly imagine the CNS destruction of tren but also the high ROI when managed correctly
Trenbolone is a synthetic steroid not naturally occurring in humans, it is a 19 nor steroid derived from nandrolone. The chemical structure of trenbolone is unique, possessing a non-present carbon 19 atom and 3 double bonds located at carbons 4, 9, and 11. These properties in the chemical structure is what causes trenbolone to exhibit its high affinity to the AR, specifically the removal of the carbon 19 methyl group. The three double bonds on tren’s steroid core makes the molecule very rigid, combining this with the fact that it is a 19 nor meaning the C19 methyl group is missing makes it not a substrate for the aromatase enzyme. This triene shape also makes it resistant to 5 alpha reductase; this is because the electrons are delocalized across the conjugated double bonds, this helps the C4 double bond in the A ring resist 5AR thus yielding no DHT.
Tren obviously is much more potent than testosterone and has a higher binding affinity to the AR, like i said earlier this is because of the C19 not being present in tren’s molecule along with the triene structure. Tren has a similar binding affinity to dihydrotestosterone. Trenblone also has a slower dissociation rate from the androgen receptor which prolongs the receptor activation which enhances androgenic signaling. Trenbolone goes through genomic and non genomic pathways. Obviously the genomic pathway goes as follows: trenbolone enters the cytoplasm of a cell then binds to the ligand binding domain of the androgen receptor. The androgen receptor dissociates from chaperone proteins, dimerizes then translocates to the nucleus. Here it binds to AREs, recruits coactivators then alters the gene transcription and pumps out a biological effect. It's all simple stuff because tren is an androgen and goes through a lot of the same pathways endogenous androgens would go through. Tren also exerts its classical AR signaling at low concentrations so you don't need a lot of tren to get results.
On the topic of genomic signalling, Tren’s unique effects on the AR come from its chemical structure. This is obvious but when an androgen binds to the ligand binding domain of the AR it changes shape and recruits co activators through the formation of AF2. This is a hydrophobic groove in the receptor that allows for coactivator proteins to bind via amino acid sequences which help activate androgenic signaling. The AR also interacts with its own AF2 via the N terminal domain binding to the AF2 that can stabilize the AR and allow for longer signaling. Ligands change the receptor shape once bound to the receptors so tren could theoretically alter the AF2 more favorably compared to other androgens. Tren’s chemical structure could potentially alter the AF2 because once an androgen is in the LBD, helix 12 keeps it inside like a door, this is where the AF2 is formed. Tren could potentially make a better geometric place in the AF2 for coactivators and N terminal domain binding. Given tren’s strong androgenic signaling and enhanced effects this is very well the case.
Obviously being an androgen it can bind to mARs and activate downstream kinase cascades that are associated with muscle protein synthesis such as PI3K/akt/mTOR and MAPK/ERK. It also stabilizes β catenin which then helps with follistatin production which can antagonize myostatin on top of the androgen inhibiting myostatin directly by binding to the AR. Also PI3K/akt activation will of course inhibit foxO which will then drop production of degrading proteins such as MuRF and atrogin 1. The local IGF1 made from tren will also lead down into mTOR via the IGF1R. I'd recommend combining tren with something like oxymetholone so that the trenbolone occupies genomic AR signalling and the oxymetholone can handle non genomic signaling.
The fact that it doesn't aromatise makes you have nice dry gains. This is another reason why tren is the mogger cutting steroid that it is, along with GR antagonism and nutrient partitioning. Another cool thing about tren is that it may bind to the mineralocorticoid receptor, this of course helps with bloat as it antagonizes aldosterone. This may be a potential benefit because as we know tren has affinity to progesterone and glucocorticoid receptors and the mineralocorticoid receptor is in the same receptor family as those two and the AR. It's not crazy to assume that tren has an antagonist effect on the MR. Especially when this was observed in vitro upon taking tren’s cytotoxicity limit of 2.29 µM and finding activity for the mineralocorticoid receptor at concentrations lower than that, implying that its actual trenbolone activity rather than cell damage.
Tren has a low binding affinity to SHBG this allows way more of the hormone to be free and bind to ARs in target cells. This is why you always want to stay on the lower end of dosing when using tren, the number may look small but due to this property it's doing a lot more than you might think just looking at the dosing number.
Trenbolone enhances wnt pathway signalling via upregulation of β catenin and inhibition of notch pathways which antagonize wnt. This is obviously important as wnt is a growth pathway that is present in muscle and bone.
Tren enters myocyte/mesenchymal precursor cell → tren exerts negative effects on GSK3 and upregulates Numb via Tcf2/Lef gene transcription → more β catenin to exert his effects via wnt pathway and notch inhibition for further wnt signaling → muscle anabolism and mesenchymal precursor cells going down myogenesis lineage
In vivo it was shown to enhance this pathway using fish fins. Studies have observed this enhancement in myoblasts but we can also attribute this same mechanism to osteoblasts.
Trenbolone binds AR → more wnt ligand is created → wnt binds to frizzled receptors thus stabilizing β catenin → β catenin levels were raised because of trenbolones negative effects on GSK3 → more β catenin to bind with tren/AR complex as co activators → translocation to nucleus → osteogenetic gene transcription such as runx2 and osterix
Further adding on this, wnt upregulates OPG via TCF/LEC/tnfrsf11b gene transcription which further prevents resorption
Speaking of trenbolone acting on bone, it was shown that in studies using rats who were skeletally mature and who were orchiectomized that trenbolone partially or completely countered the bone loss from hypogonadism and maintained bone strength, enhancing the femoral neck in the rats. It's also good to note that in the presence of AIs the BMD caused from tren didn't get messed up at all which means that trenbolone doesn't need to aromatase into e2 to exert its effects on bone
In a study done on ORX rats testosterone and trenbolone were administered in the presence of anastrozole. The osteoclast surface was reduced in both groups however AI administration with test reduced the osteoclast surface reducing effects of test to that of SHAMs, while AI coadministration with tren resulted in zero reduction in trens osteoclast surface reducing effects. Maximum breaking loads of the femoral neck exceeded SHAMs in ORX + tren rats and was comparable to SHAMs in ORX + tren + AI rats. LABC mass was also greater in rats treated with tren compared to SHAMs, roughly 38-42% greater.
In the same study TE and tren also reduced the osteoblast surfaces in the bone that were caused from a high turnover rate due to ORX. This shows that the androgens reduced the turnover rate in hypogonadal rats and like the first statement, AI administration didn't change reduce trens effects
Gluticorticoid Receptor Antagonist
This is why tren mogs so hard while cutting, it just blocks the catabolic effects of cortisol. Tren decreases the amount of GR mRNA and also binds to the GR further antagonizing cortisol
The anti catabolic effects are not only in muscle as they are expressed in bone. GRs inhabit bone cells and cortisol can bind with them and increase sclerostin secretion and disrupt the OPG/RANKL axis and inhibits the wnt pathway which ultimately leads to osteoclastogenesis and bone resorption. Once tren enters this whole cascade just gets antagonized
IGF-1
Trenbolone makes you more sensitive to IGF1, in rat satellite cells it was shown that rats treated with tren had way more proliferation. In contrast it was shown that if you place tren directly in the medium of cultured satellite cells it did not have any proliferative effects. Comparing this with satellite cells from rats treated with tren who had greater proliferative effects to FGF and IGF1 clearly showing an increased sensitivity. So on top of potent paracrine IGF1 signalling, it contributes to increased systemic IGF1.
IGF1 also contributes to bone via IGF1R/akt+PI3K/mTOR activation which leads to the proliferation of osteblasts
Nutritional Parting
This refers to how much of your nutrients/calories goes to muscle or fat. Trenbolone has insane nutrient partitioning properties that make it so you can eat in a surplus and hardly gain any fat at all as it overwhelming goes to muscle tissue
This is caused by the increase of nitrogen retention in muscle tissues which drives better intake of nutrients to muscle. Tren also has positive effects on lipolysis so therefore there's not gonna be as much nutrients being stored as fat. Tren also improves glycogen stores in muscles which naturally makes you recover faster.
For an example let's say before tren 60% of your nutrients went to fat and 40% of it went to muscle, while on tren 70% will go to muscle while 30% will go to fat.
Side Effects
Gyno
Tren's strong affinity for the PR increases prolactin which can cause gyno
Neurotoxicity
Tren is neurotoxic. It can shorten neurites and cause neuron apoptosis. Tren accumulates a lot in your hippocampus, causing hippocampal neuron death and raising Aβ42 and caspase 3 levels essentially degrading your brain through the same pathways as alzheimer's disease. Along with that it also disrupts presenilin 1 and this is where it can mess with APP peptide production which leads to the upregulation of Aβ42 like we stated earlier.
Tren accumulates in hippocampus → decreases presenilin 1 and upregulates Aβ42 and caspase 3 activity → neurodegeneration/neuron apoptosis
Going along with AD like symptoms we have the fact that tren exacerbates TNF-α and IL1β inflammation which leads to activation of the hepatic IL6 inflammatory pathway which enhances release of LCN2 which then comes into the brain and expresses itself in the mPFC. This neurovisceral circuit eventually leads to the deposition of Aβ proteins which as you know is the pathway of which AD takes its toll.
Tren exacerbates TNF-α and IL1β → triggers hepatic IL6 inflammatory pathway → enhanced secretion of LCN2 which expresses itself in the brain → Aβ deposition → neurodegeneration
Tren increases neuroinflammation such as NLRP3 inflammasome, IL-6, IL-1α, and IL-1β as well as increasing proapoptotic proteins like caspase 3/7 and Bax while lowering anti apoptotic proteins such as DJ-1 and Bcl-1
Tren enters CNS → NLRP3 IL6 IL-1α IL-1β caspase 3/7 Bax increase Bcl-1 and DJ-1 decrease, tyrosine hydrolase reduction → domaminergic neuronal death worsening/neuronal apoptosis/dopamine pathway damage/substantia nigra damage
Tren causes declined mitochondrial function and causes lactate dehydrogenase release. This release is a marker of membrane damage and cell death. This mitochondrial decline comes from the neuroinflammatory cytokines I listed above, inhibition of neuroprotective proteins, as well as AR mediated pathways and oxidative stress.
Trensomnia is an effect you've heard thrown around if you know anything about tren, this is caused from an upregulation of orexin signaling which promotes wakefulness. Tren also disturbs motoneuron development and locomotion.
Tren enters CNS → upregulates orexin signaling → insomnia phenotype
I don't really know where to put this so fuck it, the thyroid is close enough to the brain. Tren suppresses t4 → t3 conversion
Tren creates a ton of ROS via an upregulation of nox, specifically hydroxyl radicals, the most destructive free radical, thus throwing off the balance of oxidants and antioxidants which then leads to oxidative stress.
Mental Side Effects
Tren can make you aggressive, this mechanism acts on NMDARs. Tren reduces these receptors in your hippocampus as well as your hypothalamus.
Anxiety is also a possibility on tren, the proposed mechanism is altering of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex. This can disrupt cortical glutamate making it increase and cause excitotoxicity and localized hypo reactivity which is linked to anxiety and social avoidance
Trenbolone suppresses endogenous testosterone and disturbs the TACR3 pathway in the hippocampus and thus inducing abnormal synaptic transmission signaling in the hippocampus, down regulation of synaptic proteins: PSD95, syn, gephyrin as well as metabolic imbalance in glutamate/GABA signaling. However having a test base will alleviate this, as observed in the rat study
Tren crosses BBB → down regulation of PSD95, syn, gephyrin, GABA/glutamate metabolic imbalance, down regulation of TACR3 hippocampus pathway → impaired synaptic plasticity and emotion regulation → anxiety behavior
Tren crosses BBB and disrupts maturation of oligodendrocytes → increase in glutamate and disruption of formation of the myelin sheath → excitotoxicity in the mPFC → anxiety
Trenbolone causes GABAergic disinhibition, tren can bind with GABAa receptors and make them go under allosteric modulation, modification of neuronal transmission and the activation and sensitivity of these receptors. As we know GABA is the inhibitory signals in your brain that calms your CNS, tren can basically change the way these receptors work to make you lower inhib and more aggressive
Tren crosses BBB → binds to GABAa receptors in the CNS → allosteric modulation of GABAa receptors → lower inhib/less inhibitory signals in CNS → impulsive behavior
Trenbolone of course suppresses the HPG axis and in a mice study this was found to disrupt sex steroids of course, altering AR and ERa levels in the testis. Tren also caused more dominant social behavior and stronger sexual attraction to females as well as males, when they checked for markers all they could find was increased c-Nos in the mPFC and the BLA.
Tren suppresses HPG axis → abnormal AR and ERa levels → disrupted sex steroid signaling → signaling in mPFC and BLA → social dominance and gayness
Proposed mechanism of course, but this could be how tren makes you gay.
19 nors cause shifts in density of serotonergic receptors in multiple regions in the brain, downregulation of 5HT1B receptor density in the hippocampus and in the medial globus pallidas. Upregulation of 5HT2 receptor density in the nucleus accumbens. Shifts in serotonergic receptors were also seen in more regions of the brain
By down regulating the 5HT1B it makes your serotonin brake not function properly and unable to inhibit impulsive behaviors, while this is happening an upregulation of 5HT2 makes it so that your reward system is hypersensitive making neutral things seem threatening and intense
Tren crosses BBB → up and down regulation of 5HT2 and 5HT1B serotonin receptors in multiple regions of the brain → Decreased impulse control and aggressive behavior
Tren isn't limited to mice studies when observing aggression, there have been studies that survey AAS users and have found a dose dependent relationship between trenbolone and verbal aggression
“After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression.”
“Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues.”
Tren not being to aromatase means there is pure androgenic signalling on your cardiovascular system without the added benefit of estrogen NO release and estrogen driven nephroprotectin. This results in high blood pressure which can also cause kidney problems. Although high creatinine is an issue, it doesn't really do much here as 19 nor cycles are relatively short.
Because estrogen cannot be provided from the trenbolone ligand, the androgenic effects on lipids is severe. Tren wrecks HDL while also raising LDL. This can lead to your arteries getting clogged and increasing workload on your cardiovascular system which therefore will lead to LVH.
Hematocrit will rise while on androgens and your blood will get thick, this is an issue because of clotting and more strain on the cardiovascular system.
Tren signals the adrenergic system which causes an overactive SNS which can narrow blood vessels forcing your heart to pump faster which leads to fast resting heart rate.
Tren also has hepatotoxic effects which in case reports was seen with severe transaminasemia which is a marker for AST/ALT enzymes in the bloodstream indicating hepatocyte injury. Also having hyperbilirubinemia caused by disrupted bile flow and also renal damage.
Liver markers showed cholestasis, sinusoidal dilation and cholangitis like changes, all are markers of hepatocyte injury and cholestatic injury.
All in all, trenbolone effects on the liver can be caused from oxidative stress, impaired bile export and disrupted hepatocyte transporter activity.
Memantine is an uncompetitive NMDA receptor antagonist that antagonizes glutamate which helps against neurodegeneration trenbolone will cause from glutamate excitotoxicity
Cerebrolysin - One Course Post Cycle
Peptide derived from pig brain with a low molecular weight allowing it to cross the BBB easily. Upregulates shh pathway to induce neural progenitor cell proliferation and oligodendrogenesis and neurogenesis. It mimics and stimulates neurotrophic growth factors in your brain like NTF3 and BDNF.
Cerebrolysin had been used for AD, traumatic brain injury and strokes with significantly beneficial results, should be able to cleave tren neurotoxicity adequately
Melatonin 100mg+
Sleep hormone that acts on MT1 and MT2 receptors to regulate circadian rhythm. At megadoses it can be a powerful antioxidant. It is a direct free radical scavenger and can neutralize a lot of ROS and RNS. It also stimulates a few antioxidant enzymes further pushing its antioxidant abilities.
Melatonin also binds to mt1 receptors on the mitochondrial membrane and dampening caspase activation through downstream pathways. Melatonin stimulates oxidative phosphorylation and promotes ATP production in neuronal and hepatocyte mitochondria.
Very mogger molecule that keeps cells safe from oxidative stress whilst also neutralizing ROS and RNS. One more thing about melatonin is that it inhibits NLRP3 inflammasome which is activated by tren and is linked to apoptosis
Propronal 10mg
Competitive nonselective beta blocker that acts on receptors β1 and β2 which can help reduce adrenaline and noradrenaline signaling and dampen the somatic feedback loop and its anxiety symptoms, thus reducing impulsive behavior and aggression and could potentially help with night sweats due to a relaxed SNS and suppressed somatic feedback loop
DORAs
Dual orexin receptor antagonists, targets both OX1R and OX2R to inhibit wakefulness signals of the orexin system that induce insomnia. No dependency issues arise either.
Empagliflozin 10mg
Increases mitochondria ATP production and reduces oxidative stress making the mitochondria more efficient
NACET 100mg
N-acetylcysteine with a longer half life and better bioavailability, is a precursor to glutathione which is your body's natural antioxidant. Crosses the BBB which allows for glutathione production in the CNS
9-Me-BC
Monoamine oxidase inhibitor that upregulates tyrosine hydrolase which can lead to dopaminergic synthesis. It also creates an anti inflammatory environment by decreasing inflammatory cytokines and receptors.
In studies it was shown to reverse the domaminergic neurotoxicity from MPP and make the dopaminergic immunoreactivity cells in the striata nigra go back to normal levels after exposed neurotoxicity.
Also reduces caspase 3 activity and increases ATP content and obviously dopaminergic neuron differentiation was increased
Astaxanthin
Carotenoid that has antioxidant benefits, crosses the BBB and suppresses the NF-κB pathway and also production of inflammatory cytokines. Linking to the membrane from inside to outside allows for better biological activity. Of course donates electrons to free radicals to neutralize them as well
Cardiovascular/Liver/Kidney protection
Telmisartan 160mg
Angiotensin 2 blocker that acts on angiotensin type 1 receptors to minimize vasoconstriction caused from overactive RAAS, also nice Insulin sensitivity bonus due to partial agonism of the PPARγ
Tadalafil 5-10mg
PDE5 Inhibitor that blocks the PDE5 enzyme from breaking down cGMP which lets smooth muscle relax and blood flow commence easier
Nebivolol 5-10mg
Highly selective β1 receptor antagonist that antagonizes adrenergic signaling in the heart, therefore lowering resting heart rate. Also has antihypertensive properties due to being a β3 agonist which stimulates nitric oxide release and vasodilation
Eplerenone 50mg
Selective MR antagonist that antagonizes aldosterone, thus stopping aldosterone from inducing myocardial fibrosis
Tudca 500mg
Bile acid that helps maintain bile flow to avoid cholestasis and also supports hepatocytes from ER stress by folding proteins
NACET 100mg
Cysteine → glutathione conversion used for antioxidant and hepatoprotection
Empagliflozin 10mg
SGLT2 inhibitor that handles glucose as well as having kidney protective properties by reducing workload placed on the kidneys. Cardio protection benefits are also included
Rupatadine 10mg
Histamine antagonist with selective peripheral H1 receptor antagonist activity blocking the receptors of PAF. This helps for tren’s PAF inflammatory signalling, you can throw this into a lot of cycles with AAS due to the inflammation
Pentoxifylline 400mg
Phosphodiesterase inhibitor that makes blood less vicious and makes red blood cells more flexible via increase ethyrocyte ATP and cyclic nucleotide levels which allows blood to travel through narrow passages which will be helpful with raised hematocrit from tren
Pemafibrate 0.2mg
The superior fibrate that selectively binds to PPARa for serum triglyceride reduction as well as increasing HDL. Helps liver function and doesn't place strain on the kidneys and can be taken along side with statins due to low drug interactions
Lipids/Prolactin/Thyroid
Pitavastatin 2-4mg
HMG-CoA reductase Inhibitor which is the enzyme used by the liver to make cholesterol. This causes an inhibition of mevalonic acid which then upregulates LDL receptors in hepatocytes to make up for the inhibition. These extra receptors grab LDL from your blood stream which leads to LDL catabolism. Also increases and enhances HDL
Ezetimibe 10mg
NPC1L1 protein blocker that inhibits the reabsorption of cholesterol from the small intestine and inhibiting the amount of cholesterol hepatocytes can use, thus making your body use circulating cholesterol which can help with high cholesterol especially when paired with a statin
P5P 200mg
L-tyrosine → L-DOPA → dopamine is the pathway in which p5p enhances. P5P is the active coenzyme b6 and helps L-DOPA convert into dopamine and bind to d2 receptors in the hypothalamus which puts a brake on prolactin secretion when reaching the pituitary
Cabergolin 0.5 - 2.5mg
D2 agonist that binds to dopamine receptors in the anterior pituitary and puts a brake on prolactin secretion
T4 + T3
Inactive and active thyroid hormones that control metabolic rate among other things. Since your conversion will slow down we'll just supplement these. Make sure to taper off nearing the end of your cycle and that your natural production of these hormones have rebounded
Hair/Skin
Isotretinoin 10-40mg
Shrinks sebaceous glands and reduces sebum production for no acne
Topical Estriol
Nice addition to any skincare routine, acts on ERs in the skin to promote elastin synthesis and is especially nice when used with retinoids
ru58841/kx-826
Both topical anti androgens, works by competing for androgen receptors and binding them so androgens can't bind to the AR, essential for compounds that bypass 5 alpha reduction.
Although tren itself isn't that androgenic due to the methyl group removal, these are still a nice edition if you plan on running DHT derivatives on your cycle
Esters
Trenbolone Acetate
Fastest acting ester with a half life of approximately 1-2 days, This calls for ED or EOD injections
Trenbolone Enanthate
Longer acting ester with a half life of approximately 11 days, would still make injections EOD at least so you don't inject a ton of androgens at once and experience worse sides
Trenbolone Hexahydrolbenzoylcarbonate
Between the two other esters with a half life of approximately 8 days, nobody runs this ester due to it not being pharmaceutically produced anymore
Conclusion
Hopefully you learned something and truly imagine the CNS destruction of tren but also the high ROI when managed correctly
Trenbolone is a synthetic steroid not naturally occurring in humans, it is a 19 nor steroid derived from nandrolone. The chemical structure of trenbolone is unique, possessing a non-present carbon 19 atom and 3 double bonds located at carbons 4, 9, and 11. These properties in the chemical structure is what causes trenbolone to exhibit its high affinity to the AR, specifically the removal of the carbon 19 methyl group. The three double bonds on tren’s steroid core makes the molecule very rigid, combining this with the fact that it is a 19 nor meaning the C19 methyl group is missing makes it not a substrate for the aromatase enzyme. This triene shape also makes it resistant to 5 alpha reductase; this is because the electrons are delocalized across the conjugated double bonds, this helps the C4 double bond in the A ring resist 5AR thus yielding no DHT.
Tren obviously is much more potent than testosterone and has a higher binding affinity to the AR, like i said earlier this is because of the C19 not being present in tren’s molecule along with the triene structure. Tren has a similar binding affinity to dihydrotestosterone. Trenblone also has a slower dissociation rate from the androgen receptor which prolongs the receptor activation which enhances androgenic signaling. Trenbolone goes through genomic and non genomic pathways. Obviously the genomic pathway goes as follows: trenbolone enters the cytoplasm of a cell then binds to the ligand binding domain of the androgen receptor. The androgen receptor dissociates from chaperone proteins, dimerizes then translocates to the nucleus. Here it binds to AREs, recruits coactivators then alters the gene transcription and pumps out a biological effect. It's all simple stuff because tren is an androgen and goes through a lot of the same pathways endogenous androgens would go through. Tren also exerts its classical AR signaling at low concentrations so you don't need a lot of tren to get results.
On the topic of genomic signalling, Tren’s unique effects on the AR come from its chemical structure. This is obvious but when an androgen binds to the ligand binding domain of the AR it changes shape and recruits co activators through the formation of AF2. This is a hydrophobic groove in the receptor that allows for coactivator proteins to bind via amino acid sequences which help activate androgenic signaling. The AR also interacts with its own AF2 via the N terminal domain binding to the AF2 that can stabilize the AR and allow for longer signaling. Ligands change the receptor shape once bound to the receptors so tren could theoretically alter the AF2 more favorably compared to other androgens. Tren’s chemical structure could potentially alter the AF2 because once an androgen is in the LBD, helix 12 keeps it inside like a door, this is where the AF2 is formed. Tren could potentially make a better geometric place in the AF2 for coactivators and N terminal domain binding. Given tren’s strong androgenic signaling and enhanced effects this is very well the case.
Obviously being an androgen it can bind to mARs and activate downstream kinase cascades that are associated with muscle protein synthesis such as PI3K/akt/mTOR and MAPK/ERK. It also stabilizes β catenin which then helps with follistatin production which can antagonize myostatin on top of the androgen inhibiting myostatin directly by binding to the AR. Also PI3K/akt activation will of course inhibit foxO which will then drop production of degrading proteins such as MuRF and atrogin 1. The local IGF1 made from tren will also lead down into mTOR via the IGF1R. I'd recommend combining tren with something like oxymetholone so that the trenbolone occupies genomic AR signalling and the oxymetholone can handle non genomic signaling.
The fact that it doesn't aromatise makes you have nice dry gains. This is another reason why tren is the mogger cutting steroid that it is, along with GR antagonism and nutrient partitioning. Another cool thing about tren is that it may bind to the mineralocorticoid receptor, this of course helps with bloat as it antagonizes aldosterone. This may be a potential benefit because as we know tren has affinity to progesterone and glucocorticoid receptors and the mineralocorticoid receptor is in the same receptor family as those two and the AR. It's not crazy to assume that tren has an antagonist effect on the MR. Especially when this was observed in vitro upon taking tren’s cytotoxicity limit of 2.29 µM and finding activity for the mineralocorticoid receptor at concentrations lower than that, implying that its actual trenbolone activity rather than cell damage.
Tren has a low binding affinity to SHBG this allows way more of the hormone to be free and bind to ARs in target cells. This is why you always want to stay on the lower end of dosing when using tren, the number may look small but due to this property it's doing a lot more than you might think just looking at the dosing number.
Trenbolone enhances wnt pathway signalling via upregulation of β catenin and inhibition of notch pathways which antagonize wnt. This is obviously important as wnt is a growth pathway that is present in muscle and bone.
Tren enters myocyte/mesenchymal precursor cell → tren exerts negative effects on GSK3 and upregulates Numb via Tcf2/Lef gene transcription → more β catenin to exert his effects via wnt pathway and notch inhibition for further wnt signaling → muscle anabolism and mesenchymal precursor cells going down myogenesis lineage
In vivo it was shown to enhance this pathway using fish fins. Studies have observed this enhancement in myoblasts but we can also attribute this same mechanism to osteoblasts.
Trenbolone binds AR → more wnt ligand is created → wnt binds to frizzled receptors thus stabilizing β catenin → β catenin levels were raised because of trenbolones negative effects on GSK3 → more β catenin to bind with tren/AR complex as co activators → translocation to nucleus → osteogenetic gene transcription such as runx2 and osterix
Further adding on this, wnt upregulates OPG via TCF/LEC/tnfrsf11b gene transcription which further prevents resorption
Speaking of trenbolone acting on bone, it was shown that in studies using rats who were skeletally mature and who were orchiectomized that trenbolone partially or completely countered the bone loss from hypogonadism and maintained bone strength, enhancing the femoral neck in the rats. It's also good to note that in the presence of AIs the BMD caused from tren didn't get messed up at all which means that trenbolone doesn't need to aromatase into e2 to exert its effects on bone
In a study done on ORX rats testosterone and trenbolone were administered in the presence of anastrozole. The osteoclast surface was reduced in both groups however AI administration with test reduced the osteoclast surface reducing effects of test to that of SHAMs, while AI coadministration with tren resulted in zero reduction in trens osteoclast surface reducing effects. Maximum breaking loads of the femoral neck exceeded SHAMs in ORX + tren rats and was comparable to SHAMs in ORX + tren + AI rats. LABC mass was also greater in rats treated with tren compared to SHAMs, roughly 38-42% greater.
In the same study TE and tren also reduced the osteoblast surfaces in the bone that were caused from a high turnover rate due to ORX. This shows that the androgens reduced the turnover rate in hypogonadal rats and like the first statement, AI administration didn't change reduce trens effects
Gluticorticoid Receptor Antagonist
This is why tren mogs so hard while cutting, it just blocks the catabolic effects of cortisol. Tren decreases the amount of GR mRNA and also binds to the GR further antagonizing cortisol
The anti catabolic effects are not only in muscle as they are expressed in bone. GRs inhabit bone cells and cortisol can bind with them and increase sclerostin secretion and disrupt the OPG/RANKL axis and inhibits the wnt pathway which ultimately leads to osteoclastogenesis and bone resorption. Once tren enters this whole cascade just gets antagonized
IGF-1
Trenbolone makes you more sensitive to IGF1, in rat satellite cells it was shown that rats treated with tren had way more proliferation. In contrast it was shown that if you place tren directly in the medium of cultured satellite cells it did not have any proliferative effects. Comparing this with satellite cells from rats treated with tren who had greater proliferative effects to FGF and IGF1 clearly showing an increased sensitivity. So on top of potent paracrine IGF1 signalling, it contributes to increased systemic IGF1.
IGF1 also contributes to bone via IGF1R/akt+PI3K/mTOR activation which leads to the proliferation of osteblasts
Nutritional Parting
This refers to how much of your nutrients/calories goes to muscle or fat. Trenbolone has insane nutrient partitioning properties that make it so you can eat in a surplus and hardly gain any fat at all as it overwhelming goes to muscle tissue
This is caused by the increase of nitrogen retention in muscle tissues which drives better intake of nutrients to muscle. Tren also has positive effects on lipolysis so therefore there's not gonna be as much nutrients being stored as fat. Tren also improves glycogen stores in muscles which naturally makes you recover faster.
For an example let's say before tren 60% of your nutrients went to fat and 40% of it went to muscle, while on tren 70% will go to muscle while 30% will go to fat.
Side Effects
Gyno
Tren's strong affinity for the PR increases prolactin which can cause gyno
Neurotoxicity
Tren is neurotoxic. It can shorten neurites and cause neuron apoptosis. Tren accumulates a lot in your hippocampus, causing hippocampal neuron death and raising Aβ42 and caspase 3 levels essentially degrading your brain through the same pathways as alzheimer's disease. Along with that it also disrupts presenilin 1 and this is where it can mess with APP peptide production which leads to the upregulation of Aβ42 like we stated earlier.
Tren accumulates in hippocampus → decreases presenilin 1 and upregulates Aβ42 and caspase 3 activity → neurodegeneration/neuron apoptosis
Going along with AD like symptoms we have the fact that tren exacerbates TNF-α and IL1β inflammation which leads to activation of the hepatic IL6 inflammatory pathway which enhances release of LCN2 which then comes into the brain and expresses itself in the mPFC. This neurovisceral circuit eventually leads to the deposition of Aβ proteins which as you know is the pathway of which AD takes its toll.
Tren exacerbates TNF-α and IL1β → triggers hepatic IL6 inflammatory pathway → enhanced secretion of LCN2 which expresses itself in the brain → Aβ deposition → neurodegeneration
Tren increases neuroinflammation such as NLRP3 inflammasome, IL-6, IL-1α, and IL-1β as well as increasing proapoptotic proteins like caspase 3/7 and Bax while lowering anti apoptotic proteins such as DJ-1 and Bcl-1
Tren enters CNS → NLRP3 IL6 IL-1α IL-1β caspase 3/7 Bax increase Bcl-1 and DJ-1 decrease, tyrosine hydrolase reduction → domaminergic neuronal death worsening/neuronal apoptosis/dopamine pathway damage/substantia nigra damage
Tren causes declined mitochondrial function and causes lactate dehydrogenase release. This release is a marker of membrane damage and cell death. This mitochondrial decline comes from the neuroinflammatory cytokines I listed above, inhibition of neuroprotective proteins, as well as AR mediated pathways and oxidative stress.
Trensomnia is an effect you've heard thrown around if you know anything about tren, this is caused from an upregulation of orexin signaling which promotes wakefulness. Tren also disturbs motoneuron development and locomotion.
Tren enters CNS → upregulates orexin signaling → insomnia phenotype
I don't really know where to put this so fuck it, the thyroid is close enough to the brain. Tren suppresses t4 → t3 conversion
Tren creates a ton of ROS via an upregulation of nox, specifically hydroxyl radicals, the most destructive free radical, thus throwing off the balance of oxidants and antioxidants which then leads to oxidative stress.
Mental Side Effects
Tren can make you aggressive, this mechanism acts on NMDARs. Tren reduces these receptors in your hippocampus as well as your hypothalamus.
Anxiety is also a possibility on tren, the proposed mechanism is altering of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex. This can disrupt cortical glutamate making it increase and cause excitotoxicity and localized hypo reactivity which is linked to anxiety and social avoidance
Trenbolone suppresses endogenous testosterone and disturbs the TACR3 pathway in the hippocampus and thus inducing abnormal synaptic transmission signaling in the hippocampus, down regulation of synaptic proteins: PSD95, syn, gephyrin as well as metabolic imbalance in glutamate/GABA signaling. However having a test base will alleviate this, as observed in the rat study
Tren crosses BBB → down regulation of PSD95, syn, gephyrin, GABA/glutamate metabolic imbalance, down regulation of TACR3 hippocampus pathway → impaired synaptic plasticity and emotion regulation → anxiety behavior
Tren crosses BBB and disrupts maturation of oligodendrocytes → increase in glutamate and disruption of formation of the myelin sheath → excitotoxicity in the mPFC → anxiety
Trenbolone causes GABAergic disinhibition, tren can bind with GABAa receptors and make them go under allosteric modulation, modification of neuronal transmission and the activation and sensitivity of these receptors. As we know GABA is the inhibitory signals in your brain that calms your CNS, tren can basically change the way these receptors work to make you lower inhib and more aggressive
Tren crosses BBB → binds to GABAa receptors in the CNS → allosteric modulation of GABAa receptors → lower inhib/less inhibitory signals in CNS → impulsive behavior
Trenbolone of course suppresses the HPG axis and in a mice study this was found to disrupt sex steroids of course, altering AR and ERa levels in the testis. Tren also caused more dominant social behavior and stronger sexual attraction to females as well as males, when they checked for markers all they could find was increased c-Nos in the mPFC and the BLA.
Tren suppresses HPG axis → abnormal AR and ERa levels → disrupted sex steroid signaling → signaling in mPFC and BLA → social dominance and gayness
Proposed mechanism of course, but this could be how tren makes you gay.
19 nors cause shifts in density of serotonergic receptors in multiple regions in the brain, downregulation of 5HT1B receptor density in the hippocampus and in the medial globus pallidas. Upregulation of 5HT2 receptor density in the nucleus accumbens. Shifts in serotonergic receptors were also seen in more regions of the brain
By down regulating the 5HT1B it makes your serotonin brake not function properly and unable to inhibit impulsive behaviors, while this is happening an upregulation of 5HT2 makes it so that your reward system is hypersensitive making neutral things seem threatening and intense
Tren crosses BBB → up and down regulation of 5HT2 and 5HT1B serotonin receptors in multiple regions of the brain → Decreased impulse control and aggressive behavior
Tren isn't limited to mice studies when observing aggression, there have been studies that survey AAS users and have found a dose dependent relationship between trenbolone and verbal aggression
“After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression.”
“Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues.”
Tren not being to aromatase means there is pure androgenic signalling on your cardiovascular system without the added benefit of estrogen NO release and estrogen driven nephroprotectin. This results in high blood pressure which can also cause kidney problems. Although high creatinine is an issue, it doesn't really do much here as 19 nor cycles are relatively short.
Because estrogen cannot be provided from the trenbolone ligand, the androgenic effects on lipids is severe. Tren wrecks HDL while also raising LDL. This can lead to your arteries getting clogged and increasing workload on your cardiovascular system which therefore will lead to LVH.
Hematocrit will rise while on androgens and your blood will get thick, this is an issue because of clotting and more strain on the cardiovascular system.
Tren signals the adrenergic system which causes an overactive SNS which can narrow blood vessels forcing your heart to pump faster which leads to fast resting heart rate.
Tren also has hepatotoxic effects which in case reports was seen with severe transaminasemia which is a marker for AST/ALT enzymes in the bloodstream indicating hepatocyte injury. Also having hyperbilirubinemia caused by disrupted bile flow and also renal damage.
Liver markers showed cholestasis, sinusoidal dilation and cholangitis like changes, all are markers of hepatocyte injury and cholestatic injury.
All in all, trenbolone effects on the liver can be caused from oxidative stress, impaired bile export and disrupted hepatocyte transporter activity.
Memantine is an uncompetitive NMDA receptor antagonist that antagonizes glutamate which helps against neurodegeneration trenbolone will cause from glutamate excitotoxicity
Cerebrolysin - One Course Post Cycle
Peptide derived from pig brain with a low molecular weight allowing it to cross the BBB easily. Upregulates shh pathway to induce neural progenitor cell proliferation and oligodendrogenesis and neurogenesis. It mimics and stimulates neurotrophic growth factors in your brain like NTF3 and BDNF.
Cerebrolysin had been used for AD, traumatic brain injury and strokes with significantly beneficial results, should be able to cleave tren neurotoxicity adequately
Melatonin 100mg+
Sleep hormone that acts on MT1 and MT2 receptors to regulate circadian rhythm. At megadoses it can be a powerful antioxidant. It is a direct free radical scavenger and can neutralize a lot of ROS and RNS. It also stimulates a few antioxidant enzymes further pushing its antioxidant abilities.
Melatonin also binds to mt1 receptors on the mitochondrial membrane and dampening caspase activation through downstream pathways. Melatonin stimulates oxidative phosphorylation and promotes ATP production in neuronal and hepatocyte mitochondria.
Very mogger molecule that keeps cells safe from oxidative stress whilst also neutralizing ROS and RNS. One more thing about melatonin is that it inhibits NLRP3 inflammasome which is activated by tren and is linked to apoptosis
Propronal 10mg
Competitive nonselective beta blocker that acts on receptors β1 and β2 which can help reduce adrenaline and noradrenaline signaling and dampen the somatic feedback loop and its anxiety symptoms, thus reducing impulsive behavior and aggression and could potentially help with night sweats due to a relaxed SNS and suppressed somatic feedback loop
DORAs
Dual orexin receptor antagonists, targets both OX1R and OX2R to inhibit wakefulness signals of the orexin system that induce insomnia. No dependency issues arise either.
Empagliflozin 10mg
Increases mitochondria ATP production and reduces oxidative stress making the mitochondria more efficient
NACET 100mg
N-acetylcysteine with a longer half life and better bioavailability, is a precursor to glutathione which is your body's natural antioxidant. Crosses the BBB which allows for glutathione production in the CNS
9-Me-BC
Monoamine oxidase inhibitor that upregulates tyrosine hydrolase which can lead to dopaminergic synthesis. It also creates an anti inflammatory environment by decreasing inflammatory cytokines and receptors.
In studies it was shown to reverse the domaminergic neurotoxicity from MPP and make the dopaminergic immunoreactivity cells in the striata nigra go back to normal levels after exposed neurotoxicity.
Also reduces caspase 3 activity and increases ATP content and obviously dopaminergic neuron differentiation was increased
Astaxanthin
Carotenoid that has antioxidant benefits, crosses the BBB and suppresses the NF-κB pathway and also production of inflammatory cytokines. Linking to the membrane from inside to outside allows for better biological activity. Of course donates electrons to free radicals to neutralize them as well
Cardiovascular/Liver/Kidney protection
Telmisartan 160mg
Angiotensin 2 blocker that acts on angiotensin type 1 receptors to minimize vasoconstriction caused from overactive RAAS, also nice Insulin sensitivity bonus due to partial agonism of the PPARγ
Tadalafil 5-10mg
PDE5 Inhibitor that blocks the PDE5 enzyme from breaking down cGMP which lets smooth muscle relax and blood flow commence easier
Nebivolol 5-10mg
Highly selective β1 receptor antagonist that antagonizes adrenergic signaling in the heart, therefore lowering resting heart rate. Also has antihypertensive properties due to being a β3 agonist which stimulates nitric oxide release and vasodilation
Eplerenone 50mg
Selective MR antagonist that antagonizes aldosterone, thus stopping aldosterone from inducing myocardial fibrosis
Tudca 500mg
Bile acid that helps maintain bile flow to avoid cholestasis and also supports hepatocytes from ER stress by folding proteins
NACET 100mg
Cysteine → glutathione conversion used for antioxidant and hepatoprotection
Empagliflozin 10mg
SGLT2 inhibitor that handles glucose as well as having kidney protective properties by reducing workload placed on the kidneys. Cardio protection benefits are also included
Rupatadine 10mg
Histamine antagonist with selective peripheral H1 receptor antagonist activity blocking the receptors of PAF. This helps for tren’s PAF inflammatory signalling, you can throw this into a lot of cycles with AAS due to the inflammation
Pentoxifylline 400mg
Phosphodiesterase inhibitor that makes blood less vicious and makes red blood cells more flexible via increase ethyrocyte ATP and cyclic nucleotide levels which allows blood to travel through narrow passages which will be helpful with raised hematocrit from tren
Pemafibrate 0.2mg
The superior fibrate that selectively binds to PPARa for serum triglyceride reduction as well as increasing HDL. Helps liver function and doesn't place strain on the kidneys and can be taken along side with statins due to low drug interactions
Lipids/Prolactin/Thyroid
Pitavastatin 2-4mg
HMG-CoA reductase Inhibitor which is the enzyme used by the liver to make cholesterol. This causes an inhibition of mevalonic acid which then upregulates LDL receptors in hepatocytes to make up for the inhibition. These extra receptors grab LDL from your blood stream which leads to LDL catabolism. Also increases and enhances HDL
Ezetimibe 10mg
NPC1L1 protein blocker that inhibits the reabsorption of cholesterol from the small intestine and inhibiting the amount of cholesterol hepatocytes can use, thus making your body use circulating cholesterol which can help with high cholesterol especially when paired with a statin
P5P 200mg
L-tyrosine → L-DOPA → dopamine is the pathway in which p5p enhances. P5P is the active coenzyme b6 and helps L-DOPA convert into dopamine and bind to d2 receptors in the hypothalamus which puts a brake on prolactin secretion when reaching the pituitary
Cabergolin 0.5 - 2.5mg
D2 agonist that binds to dopamine receptors in the anterior pituitary and puts a brake on prolactin secretion
T4 + T3
Inactive and active thyroid hormones that control metabolic rate among other things. Since your conversion will slow down we'll just supplement these. Make sure to taper off nearing the end of your cycle and that your natural production of these hormones have rebounded
Hair/Skin
Isotretinoin 10-40mg
Shrinks sebaceous glands and reduces sebum production for no acne
Topical Estriol
Nice addition to any skincare routine, acts on ERs in the skin to promote elastin synthesis and is especially nice when used with retinoids
ru58841/kx-826
Both topical anti androgens, works by competing for androgen receptors and binding them so androgens can't bind to the AR, essential for compounds that bypass 5 alpha reduction.
Although tren itself isn't that androgenic due to the methyl group removal, these are still a nice edition if you plan on running DHT derivatives on your cycle
Esters
Trenbolone Acetate
Fastest acting ester with a half life of approximately 1-2 days, This calls for ED or EOD injections
Trenbolone Enanthate
Longer acting ester with a half life of approximately 11 days, would still make injections EOD at least so you don't inject a ton of androgens at once and experience worse sides
Trenbolone Hexahydrolbenzoylcarbonate
Between the two other esters with a half life of approximately 8 days, nobody runs this ester due to it not being pharmaceutically produced anymore
Conclusion
Hopefully you learned something and truly imagine the CNS destruction of tren but also the high ROI when managed correctly
Trenbolone is a synthetic steroid not naturally occurring in humans, it is a 19 nor steroid derived from nandrolone. The chemical structure of trenbolone is unique, possessing a non-present carbon 19 atom and 3 double bonds located at carbons 4, 9, and 11. These properties in the chemical structure is what causes trenbolone to exhibit its high affinity to the AR, specifically the removal of the carbon 19 methyl group. The three double bonds on tren’s steroid core makes the molecule very rigid, combining this with the fact that it is a 19 nor meaning the C19 methyl group is missing makes it not a substrate for the aromatase enzyme. This triene shape also makes it resistant to 5 alpha reductase; this is because the electrons are delocalized across the conjugated double bonds, this helps the C4 double bond in the A ring resist 5AR thus yielding no DHT.
Tren obviously is much more potent than testosterone and has a higher binding affinity to the AR, like i said earlier this is because of the C19 not being present in tren’s molecule along with the triene structure. Tren has a similar binding affinity to dihydrotestosterone. Trenblone also has a slower dissociation rate from the androgen receptor which prolongs the receptor activation which enhances androgenic signaling. Trenbolone goes through genomic and non genomic pathways. Obviously the genomic pathway goes as follows: trenbolone enters the cytoplasm of a cell then binds to the ligand binding domain of the androgen receptor. The androgen receptor dissociates from chaperone proteins, dimerizes then translocates to the nucleus. Here it binds to AREs, recruits coactivators then alters the gene transcription and pumps out a biological effect. It's all simple stuff because tren is an androgen and goes through a lot of the same pathways endogenous androgens would go through. Tren also exerts its classical AR signaling at low concentrations so you don't need a lot of tren to get results.
On the topic of genomic signalling, Tren’s unique effects on the AR come from its chemical structure. This is obvious but when an androgen binds to the ligand binding domain of the AR it changes shape and recruits co activators through the formation of AF2. This is a hydrophobic groove in the receptor that allows for coactivator proteins to bind via amino acid sequences which help activate androgenic signaling. The AR also interacts with its own AF2 via the N terminal domain binding to the AF2 that can stabilize the AR and allow for longer signaling. Ligands change the receptor shape once bound to the receptors so tren could theoretically alter the AF2 more favorably compared to other androgens. Tren’s chemical structure could potentially alter the AF2 because once an androgen is in the LBD, helix 12 keeps it inside like a door, this is where the AF2 is formed. Tren could potentially make a better geometric place in the AF2 for coactivators and N terminal domain binding. Given tren’s strong androgenic signaling and enhanced effects this is very well the case.
Obviously being an androgen it can bind to mARs and activate downstream kinase cascades that are associated with muscle protein synthesis such as PI3K/akt/mTOR and MAPK/ERK. It also stabilizes β catenin which then helps with follistatin production which can antagonize myostatin on top of the androgen inhibiting myostatin directly by binding to the AR. Also PI3K/akt activation will of course inhibit foxO which will then drop production of degrading proteins such as MuRF and atrogin 1. The local IGF1 made from tren will also lead down into mTOR via the IGF1R. I'd recommend combining tren with something like oxymetholone so that the trenbolone occupies genomic AR signalling and the oxymetholone can handle non genomic signaling.
The fact that it doesn't aromatise makes you have nice dry gains. This is another reason why tren is the mogger cutting steroid that it is, along with GR antagonism and nutrient partitioning. Another cool thing about tren is that it may bind to the mineralocorticoid receptor, this of course helps with bloat as it antagonizes aldosterone. This may be a potential benefit because as we know tren has affinity to progesterone and glucocorticoid receptors and the mineralocorticoid receptor is in the same receptor family as those two and the AR. It's not crazy to assume that tren has an antagonist effect on the MR. Especially when this was observed in vitro upon taking tren’s cytotoxicity limit of 2.29 µM and finding activity for the mineralocorticoid receptor at concentrations lower than that, implying that its actual trenbolone activity rather than cell damage.
Tren has a low binding affinity to SHBG this allows way more of the hormone to be free and bind to ARs in target cells. This is why you always want to stay on the lower end of dosing when using tren, the number may look small but due to this property it's doing a lot more than you might think just looking at the dosing number.
Trenbolone enhances wnt pathway signalling via upregulation of β catenin and inhibition of notch pathways which antagonize wnt. This is obviously important as wnt is a growth pathway that is present in muscle and bone.
Tren enters myocyte/mesenchymal precursor cell → tren exerts negative effects on GSK3 and upregulates Numb via Tcf2/Lef gene transcription → more β catenin to exert his effects via wnt pathway and notch inhibition for further wnt signaling → muscle anabolism and mesenchymal precursor cells going down myogenesis lineage
In vivo it was shown to enhance this pathway using fish fins. Studies have observed this enhancement in myoblasts but we can also attribute this same mechanism to osteoblasts.
Trenbolone binds AR → more wnt ligand is created → wnt binds to frizzled receptors thus stabilizing β catenin → β catenin levels were raised because of trenbolones negative effects on GSK3 → more β catenin to bind with tren/AR complex as co activators → translocation to nucleus → osteogenetic gene transcription such as runx2 and osterix
Further adding on this, wnt upregulates OPG via TCF/LEC/tnfrsf11b gene transcription which further prevents resorption
Speaking of trenbolone acting on bone, it was shown that in studies using rats who were skeletally mature and who were orchiectomized that trenbolone partially or completely countered the bone loss from hypogonadism and maintained bone strength, enhancing the femoral neck in the rats. It's also good to note that in the presence of AIs the BMD caused from tren didn't get messed up at all which means that trenbolone doesn't need to aromatase into e2 to exert its effects on bone
In a study done on ORX rats testosterone and trenbolone were administered in the presence of anastrozole. The osteoclast surface was reduced in both groups however AI administration with test reduced the osteoclast surface reducing effects of test to that of SHAMs, while AI coadministration with tren resulted in zero reduction in trens osteoclast surface reducing effects. Maximum breaking loads of the femoral neck exceeded SHAMs in ORX + tren rats and was comparable to SHAMs in ORX + tren + AI rats. LABC mass was also greater in rats treated with tren compared to SHAMs, roughly 38-42% greater.
In the same study TE and tren also reduced the osteoblast surfaces in the bone that were caused from a high turnover rate due to ORX. This shows that the androgens reduced the turnover rate in hypogonadal rats and like the first statement, AI administration didn't change reduce trens effects
Gluticorticoid Receptor Antagonist
This is why tren mogs so hard while cutting, it just blocks the catabolic effects of cortisol. Tren decreases the amount of GR mRNA and also binds to the GR further antagonizing cortisol
The anti catabolic effects are not only in muscle as they are expressed in bone. GRs inhabit bone cells and cortisol can bind with them and increase sclerostin secretion and disrupt the OPG/RANKL axis and inhibits the wnt pathway which ultimately leads to osteoclastogenesis and bone resorption. Once tren enters this whole cascade just gets antagonized
IGF-1
Trenbolone makes you more sensitive to IGF1, in rat satellite cells it was shown that rats treated with tren had way more proliferation. In contrast it was shown that if you place tren directly in the medium of cultured satellite cells it did not have any proliferative effects. Comparing this with satellite cells from rats treated with tren who had greater proliferative effects to FGF and IGF1 clearly showing an increased sensitivity. So on top of potent paracrine IGF1 signalling, it contributes to increased systemic IGF1.
IGF1 also contributes to bone via IGF1R/akt+PI3K/mTOR activation which leads to the proliferation of osteblasts
Nutritional Parting
This refers to how much of your nutrients/calories goes to muscle or fat. Trenbolone has insane nutrient partitioning properties that make it so you can eat in a surplus and hardly gain any fat at all as it overwhelming goes to muscle tissue
This is caused by the increase of nitrogen retention in muscle tissues which drives better intake of nutrients to muscle. Tren also has positive effects on lipolysis so therefore there's not gonna be as much nutrients being stored as fat. Tren also improves glycogen stores in muscles which naturally makes you recover faster.
For an example let's say before tren 60% of your nutrients went to fat and 40% of it went to muscle, while on tren 70% will go to muscle while 30% will go to fat.
Side Effects
Gyno
Tren's strong affinity for the PR increases prolactin which can cause gyno
Neurotoxicity
Tren is neurotoxic. It can shorten neurites and cause neuron apoptosis. Tren accumulates a lot in your hippocampus, causing hippocampal neuron death and raising Aβ42 and caspase 3 levels essentially degrading your brain through the same pathways as alzheimer's disease. Along with that it also disrupts presenilin 1 and this is where it can mess with APP peptide production which leads to the upregulation of Aβ42 like we stated earlier.
Tren accumulates in hippocampus → decreases presenilin 1 and upregulates Aβ42 and caspase 3 activity → neurodegeneration/neuron apoptosis
Going along with AD like symptoms we have the fact that tren exacerbates TNF-α and IL1β inflammation which leads to activation of the hepatic IL6 inflammatory pathway which enhances release of LCN2 which then comes into the brain and expresses itself in the mPFC. This neurovisceral circuit eventually leads to the deposition of Aβ proteins which as you know is the pathway of which AD takes its toll.
Tren exacerbates TNF-α and IL1β → triggers hepatic IL6 inflammatory pathway → enhanced secretion of LCN2 which expresses itself in the brain → Aβ deposition → neurodegeneration
Tren increases neuroinflammation such as NLRP3 inflammasome, IL-6, IL-1α, and IL-1β as well as increasing proapoptotic proteins like caspase 3/7 and Bax while lowering anti apoptotic proteins such as DJ-1 and Bcl-1
Tren enters CNS → NLRP3 IL6 IL-1α IL-1β caspase 3/7 Bax increase Bcl-1 and DJ-1 decrease, tyrosine hydrolase reduction → domaminergic neuronal death worsening/neuronal apoptosis/dopamine pathway damage/substantia nigra damage
Tren causes declined mitochondrial function and causes lactate dehydrogenase release. This release is a marker of membrane damage and cell death. This mitochondrial decline comes from the neuroinflammatory cytokines I listed above, inhibition of neuroprotective proteins, as well as AR mediated pathways and oxidative stress.
Trensomnia is an effect you've heard thrown around if you know anything about tren, this is caused from an upregulation of orexin signaling which promotes wakefulness. Tren also disturbs motoneuron development and locomotion.
Tren enters CNS → upregulates orexin signaling → insomnia phenotype
I don't really know where to put this so fuck it, the thyroid is close enough to the brain. Tren suppresses t4 → t3 conversion
Tren creates a ton of ROS via an upregulation of nox, specifically hydroxyl radicals, the most destructive free radical, thus throwing off the balance of oxidants and antioxidants which then leads to oxidative stress.
Mental Side Effects
Tren can make you aggressive, this mechanism acts on NMDARs. Tren reduces these receptors in your hippocampus as well as your hypothalamus.
Anxiety is also a possibility on tren, the proposed mechanism is altering of oligodendrocytes and the formation of the myelin sheath in the medial prefrontal cortex. This can disrupt cortical glutamate making it increase and cause excitotoxicity and localized hypo reactivity which is linked to anxiety and social avoidance
Trenbolone suppresses endogenous testosterone and disturbs the TACR3 pathway in the hippocampus and thus inducing abnormal synaptic transmission signaling in the hippocampus, down regulation of synaptic proteins: PSD95, syn, gephyrin as well as metabolic imbalance in glutamate/GABA signaling. However having a test base will alleviate this, as observed in the rat study
Tren crosses BBB → down regulation of PSD95, syn, gephyrin, GABA/glutamate metabolic imbalance, down regulation of TACR3 hippocampus pathway → impaired synaptic plasticity and emotion regulation → anxiety behavior
Tren crosses BBB and disrupts maturation of oligodendrocytes → increase in glutamate and disruption of formation of the myelin sheath → excitotoxicity in the mPFC → anxiety
Trenbolone causes GABAergic disinhibition, tren can bind with GABAa receptors and make them go under allosteric modulation, modification of neuronal transmission and the activation and sensitivity of these receptors. As we know GABA is the inhibitory signals in your brain that calms your CNS, tren can basically change the way these receptors work to make you lower inhib and more aggressive
Tren crosses BBB → binds to GABAa receptors in the CNS → allosteric modulation of GABAa receptors → lower inhib/less inhibitory signals in CNS → impulsive behavior
Trenbolone of course suppresses the HPG axis and in a mice study this was found to disrupt sex steroids of course, altering AR and ERa levels in the testis. Tren also caused more dominant social behavior and stronger sexual attraction to females as well as males, when they checked for markers all they could find was increased c-Nos in the mPFC and the BLA.
Tren suppresses HPG axis → abnormal AR and ERa levels → disrupted sex steroid signaling → signaling in mPFC and BLA → social dominance and gayness
Proposed mechanism of course, but this could be how tren makes you gay.
19 nors cause shifts in density of serotonergic receptors in multiple regions in the brain, downregulation of 5HT1B receptor density in the hippocampus and in the medial globus pallidas. Upregulation of 5HT2 receptor density in the nucleus accumbens. Shifts in serotonergic receptors were also seen in more regions of the brain
By down regulating the 5HT1B it makes your serotonin brake not function properly and unable to inhibit impulsive behaviors, while this is happening an upregulation of 5HT2 makes it so that your reward system is hypersensitive making neutral things seem threatening and intense
Tren crosses BBB → up and down regulation of 5HT2 and 5HT1B serotonin receptors in multiple regions of the brain → Decreased impulse control and aggressive behavior
Tren isn't limited to mice studies when observing aggression, there have been studies that survey AAS users and have found a dose dependent relationship between trenbolone and verbal aggression
“After controlling for age and BMI, dose of trenbolone was significantly (p=0.045) associated with higher levels of verbal aggression.”
“Of all the AAS, trenbolone was viewed as having the most deleterious consequences for those who used it. Users reported an extreme shift in risk profile for psychosocial harms, particularly increased aggression and violent behaviour, as well as impulsivity regulation issues.”
Tren not being to aromatase means there is pure androgenic signalling on your cardiovascular system without the added benefit of estrogen NO release and estrogen driven nephroprotectin. This results in high blood pressure which can also cause kidney problems. Although high creatinine is an issue, it doesn't really do much here as 19 nor cycles are relatively short.
Because estrogen cannot be provided from the trenbolone ligand, the androgenic effects on lipids is severe. Tren wrecks HDL while also raising LDL. This can lead to your arteries getting clogged and increasing workload on your cardiovascular system which therefore will lead to LVH.
Hematocrit will rise while on androgens and your blood will get thick, this is an issue because of clotting and more strain on the cardiovascular system.
Tren signals the adrenergic system which causes an overactive SNS which can narrow blood vessels forcing your heart to pump faster which leads to fast resting heart rate.
Tren also has hepatotoxic effects which in case reports was seen with severe transaminasemia which is a marker for AST/ALT enzymes in the bloodstream indicating hepatocyte injury. Also having hyperbilirubinemia caused by disrupted bile flow and also renal damage.
Liver markers showed cholestasis, sinusoidal dilation and cholangitis like changes, all are markers of hepatocyte injury and cholestatic injury.
All in all, trenbolone effects on the liver can be caused from oxidative stress, impaired bile export and disrupted hepatocyte transporter activity.
Memantine is an uncompetitive NMDA receptor antagonist that antagonizes glutamate which helps against neurodegeneration trenbolone will cause from glutamate excitotoxicity
Cerebrolysin - One Course Post Cycle
Peptide derived from pig brain with a low molecular weight allowing it to cross the BBB easily. Upregulates shh pathway to induce neural progenitor cell proliferation and oligodendrogenesis and neurogenesis. It mimics and stimulates neurotrophic growth factors in your brain like NTF3 and BDNF.
Cerebrolysin had been used for AD, traumatic brain injury and strokes with significantly beneficial results, should be able to cleave tren neurotoxicity adequately
Melatonin 100mg+
Sleep hormone that acts on MT1 and MT2 receptors to regulate circadian rhythm. At megadoses it can be a powerful antioxidant. It is a direct free radical scavenger and can neutralize a lot of ROS and RNS. It also stimulates a few antioxidant enzymes further pushing its antioxidant abilities.
Melatonin also binds to mt1 receptors on the mitochondrial membrane and dampening caspase activation through downstream pathways. Melatonin stimulates oxidative phosphorylation and promotes ATP production in neuronal and hepatocyte mitochondria.
Very mogger molecule that keeps cells safe from oxidative stress whilst also neutralizing ROS and RNS. One more thing about melatonin is that it inhibits NLRP3 inflammasome which is activated by tren and is linked to apoptosis
Propronal 10mg
Competitive nonselective beta blocker that acts on receptors β1 and β2 which can help reduce adrenaline and noradrenaline signaling and dampen the somatic feedback loop and its anxiety symptoms, thus reducing impulsive behavior and aggression and could potentially help with night sweats due to a relaxed SNS and suppressed somatic feedback loop
DORAs
Dual orexin receptor antagonists, targets both OX1R and OX2R to inhibit wakefulness signals of the orexin system that induce insomnia. No dependency issues arise either.
Empagliflozin 10mg
Increases mitochondria ATP production and reduces oxidative stress making the mitochondria more efficient
NACET 100mg
N-acetylcysteine with a longer half life and better bioavailability, is a precursor to glutathione which is your body's natural antioxidant. Crosses the BBB which allows for glutathione production in the CNS
9-Me-BC
Monoamine oxidase inhibitor that upregulates tyrosine hydrolase which can lead to dopaminergic synthesis. It also creates an anti inflammatory environment by decreasing inflammatory cytokines and receptors.
In studies it was shown to reverse the domaminergic neurotoxicity from MPP and make the dopaminergic immunoreactivity cells in the striata nigra go back to normal levels after exposed neurotoxicity.
Also reduces caspase 3 activity and increases ATP content and obviously dopaminergic neuron differentiation was increased
Astaxanthin
Carotenoid that has antioxidant benefits, crosses the BBB and suppresses the NF-κB pathway and also production of inflammatory cytokines. Linking to the membrane from inside to outside allows for better biological activity. Of course donates electrons to free radicals to neutralize them as well
Cardiovascular/Liver/Kidney protection
Telmisartan 160mg
Angiotensin 2 blocker that acts on angiotensin type 1 receptors to minimize vasoconstriction caused from overactive RAAS, also nice Insulin sensitivity bonus due to partial agonism of the PPARγ
Tadalafil 5-10mg
PDE5 Inhibitor that blocks the PDE5 enzyme from breaking down cGMP which lets smooth muscle relax and blood flow commence easier
Nebivolol 5-10mg
Highly selective β1 receptor antagonist that antagonizes adrenergic signaling in the heart, therefore lowering resting heart rate. Also has antihypertensive properties due to being a β3 agonist which stimulates nitric oxide release and vasodilation
Eplerenone 50mg
Selective MR antagonist that antagonizes aldosterone, thus stopping aldosterone from inducing myocardial fibrosis
Tudca 500mg
Bile acid that helps maintain bile flow to avoid cholestasis and also supports hepatocytes from ER stress by folding proteins
NACET 100mg
Cysteine → glutathione conversion used for antioxidant and hepatoprotection
Empagliflozin 10mg
SGLT2 inhibitor that handles glucose as well as having kidney protective properties by reducing workload placed on the kidneys. Cardio protection benefits are also included
Rupatadine 10mg
Histamine antagonist with selective peripheral H1 receptor antagonist activity blocking the receptors of PAF. This helps for tren’s PAF inflammatory signalling, you can throw this into a lot of cycles with AAS due to the inflammation
Pentoxifylline 400mg
Phosphodiesterase inhibitor that makes blood less vicious and makes red blood cells more flexible via increase ethyrocyte ATP and cyclic nucleotide levels which allows blood to travel through narrow passages which will be helpful with raised hematocrit from tren
Pemafibrate 0.2mg
The superior fibrate that selectively binds to PPARa for serum triglyceride reduction as well as increasing HDL. Helps liver function and doesn't place strain on the kidneys and can be taken along side with statins due to low drug interactions
Lipids/Prolactin/Thyroid
Pitavastatin 2-4mg
HMG-CoA reductase Inhibitor which is the enzyme used by the liver to make cholesterol. This causes an inhibition of mevalonic acid which then upregulates LDL receptors in hepatocytes to make up for the inhibition. These extra receptors grab LDL from your blood stream which leads to LDL catabolism. Also increases and enhances HDL
Ezetimibe 10mg
NPC1L1 protein blocker that inhibits the reabsorption of cholesterol from the small intestine and inhibiting the amount of cholesterol hepatocytes can use, thus making your body use circulating cholesterol which can help with high cholesterol especially when paired with a statin
P5P 200mg
L-tyrosine → L-DOPA → dopamine is the pathway in which p5p enhances. P5P is the active coenzyme b6 and helps L-DOPA convert into dopamine and bind to d2 receptors in the hypothalamus which puts a brake on prolactin secretion when reaching the pituitary
Cabergolin 0.5 - 2.5mg
D2 agonist that binds to dopamine receptors in the anterior pituitary and puts a brake on prolactin secretion
T4 + T3
Inactive and active thyroid hormones that control metabolic rate among other things. Since your conversion will slow down we'll just supplement these. Make sure to taper off nearing the end of your cycle and that your natural production of these hormones have rebounded
Hair/Skin
Isotretinoin 10-40mg
Shrinks sebaceous glands and reduces sebum production for no acne
Topical Estriol
Nice addition to any skincare routine, acts on ERs in the skin to promote elastin synthesis and is especially nice when used with retinoids
ru58841/kx-826
Both topical anti androgens, works by competing for androgen receptors and binding them so androgens can't bind to the AR, essential for compounds that bypass 5 alpha reduction.
Although tren itself isn't that androgenic due to the methyl group removal, these are still a nice edition if you plan on running DHT derivatives on your cycle
Esters
Trenbolone Acetate
Fastest acting ester with a half life of approximately 1-2 days, This calls for ED or EOD injections
Trenbolone Enanthate
Longer acting ester with a half life of approximately 11 days, would still make injections EOD at least so you don't inject a ton of androgens at once and experience worse sides
Trenbolone Hexahydrolbenzoylcarbonate
Between the two other esters with a half life of approximately 8 days, nobody runs this ester due to it not being pharmaceutically produced anymore
Conclusion
Hopefully you learned something and truly imagine the CNS destruction of tren but also the high ROI when managed correctly
this n***a @Epic09 followed @Balenci on TikTok then screenshotted a video of her biting her lip and made it his avi and proceeded to make 50 threads thirsting over her
this n***a @Epic09 followed @Balenci on TikTok then screenshotted a video of her biting her lip and made it his avi and proceeded to make 50 threads thirsting over her
im only gonna microdose (100mg a week) since the main roid im using is gonna be anavar, but if i cant buy var and get impatient ill just bump it up closer to 200 mg a week
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