Bigmurph6
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The Science of Trenbolone, Part 2
In the last article, we covered a lot of ground, focusing primarily on the history of trenbolone as well as its metabolic fate in mammals. If you have not already read part one, I’d urge you to go back and give it a read before moving on, as some of the topics covered there will be expanded upon in this article.
VI. Effects on HPG Axis
In vertebrates, the hypothalamic-pituitary-gonadal (HPG) axis controls reproductive processes through a variety of hormones which act on target tissues either directly or indirectly. At a high level, in males, gonadotropin-releasing hormone (GnRH) released from the hypothalamus stimulates the pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). These, in turn, stimulate the release of sex-hormones from the testes [1–2]. The strongly interwoven nature of the HPG axis means that no single component of the system operates in isolation. Upon entering circulation, both androgenic and estrogenic hormones are capable of crossing the blood-brain barrier and exerting negative feedback inhibition on the pituitary and hypothalamus, thereby downregulating GnRH release and suppressing the entire axis [3].
The administration of trenbolone is associated with numerous types of HPG axis disruptions, which is in line with what has been witnessed with various other androgen treatments over the years [4]. Some of the trenbolone-induced disruptions seen over the years include reduced levels of serum LH [5, 6, 7, 8, 9, 10], reduced serum FSH levels [11], reduced testosterone levels [5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16], reduced DHT levels [11], reduced estradiol levels [13,15], testicular atrophy [7,17–18], and a delayed onset of puberty [19]. These effects occur quite rapidly as, was demonstrated in one trial, within ten days of trenbolone enanthate administration, castrated rats had 80% suppression rates of serum testosterone and 70% suppression rates of DHT as compared to control animals [20]. It is worth noting, enanthate is a long ester variant of trenbolone (TBE) so the use of acetate (TBA) would have produced these effects even more rapidly.
It is not precisely understood what mechanisms are behind trenbolone’s suppressive effects on the HPG axis, however there have certainly been some trials over the years which provide clues. One popular hypothesis involves direct hypothalamic feedback inhibition, as evidenced by reduced GnRH transcription seen in the brains of fish models. This may be additive to its direct effects on testicular steroid biosynthesis, as supported by downregulated expression of testicular CYP17 [21]. CYP17 is a very important enzyme in steroid biosynthesis, and sequentially catalyzes two key reactions in the production of sex steroids in males.
It is also interesting to note that whatever the mechanism is, it does not appear to be androgen receptor (AR) dependent [22–23]. Further supporting this line of thought, in ovary tissue cultures from fish, non-aromatizable androgens such as trenbolone had direct and non-genomic, anti-androgen-insensitive inhibitory, effects on estrogen production [24]. It is highly likely that the underlying feedback mechanisms at work are similar to other androgens, resulting in inhibited GnRH levels and ultimately inhibited FSH and LH production [25].
One other potential gene candidate involved in decreased sex steroid concentrations, noted in fish trials in which they had been exposed to the strong exogenous androgen 17-trenbolone, is hydroxysteroid (17β) dehydrogenase 12a (hsd17b12a). Hsd17b12a catalyzes the conversion of androstenedione to testosterone which, in turn, is converted to 17β-estradiol by the aromatase enzymes. Thus, down-regulation of hsd17b12a, as seen in these trenbolone-exposed fish, is predictably expected to lead to declines in both testosterone and estradiol [14].
VII. Effects on Anabolic Pathways
As we’ve covered previously, trenbolone expresses SARM-like behaviors and I’d like to use this section to discuss them in more depth.
5α REDUCTASE
Despite a structural similarity to testosterone, trenbolone does not undergo 5α reduction due to the presence of a 3-oxotriene structure which prevents A ring reduction [26]. This is the pathway used for converting testosterone into its more potent form dihydrotestosterone (DHT). As trenbolone is not a substrate for 5α reductase, it has been shown to stimulate less pronounced androgenic effects than testosterone in androgen-sensitive tissues which express the 5α reductase enzyme, including the prostate and accessory sex organs [27, 28, 29. 30. 31, 32]. To put this statement into perspective, testosterone has an approximately three-fold higher potency in androgenic tissues that express 5α reductase despite having a significantly lower binding affinity to the AR than trenbolone [33]. We’ll discuss how this impacts hypertrophy potential in these tissues a bit later.
As you can already start to imagine, one particular reason trenbolone is beginning to pick up steam in scientific communities is due to its potential to lower the risks associated with prostate cancer in those patients being treated for hypogonadism. The current de facto treatment strategy for these individuals includes providing them with testosterone, in a manner designed to restore hormone levels to natural reference ranges. However, in adult males, benign and malignant growth of the glandular prostate tissue is largely regulated by sex hormones. And furthermore even moderate increases in circulating testosterone have been shown to directly translate into pronounced hyperplastic effects in prostate tissues, mediated via its 5α reduction into DHT [34–35]. Later in the article, we’ll dig deeper into the available literature to see if trenbolone’s potential to lower prostate cancer risk actually pans out.
AROMATASE ENZYME
Seemingly one of the more asked about questions is whether or not trenbolone has impacts on serum estrogen levels, as well as whether or not it can aromatize like testosterone. Popular opinion in the scientific community is that trenbolone and other 19-nor compounds are not substrates for the aromatase enzyme [36–37]. With that said, please understand this is not the same thing as saying they cannot convert to estrogen as C19 norandrogens can induce estrogenic effects [38–39].
Following this line of thought, trenbolone-itself is largely thought to be non-estrogenic [40–41] and there have been numerous animal trials that have demonstrated it reduces serum estradiol concentrations [13, 14, 15, 42, 43, 44]. Keep in mind that there have been a few trials that did not show this suppressive effect on estrogen levels [10,45–46] but, by and large, the body of literature as a whole does support the hypothesis that trenbolone possesses anti-estrogenic effects.
Based upon what we now know about the HPG axis, this would tend to make a lot of sense as the anti-estrogenic effects caused by trenbolone administration likely have to do with its negative feedback on the axis. This negative feedback would cause the inhibition of endogenous testosterone production, thereby leading to suppressed levels of aromatization via the aromatase enzyme, which is necessary for endogenous estrogen biosynthesis in males. This impact on the HPG axis would cause a more severe rate of estrogen inhibition as compared to any potential direct effects trenbolone would have on estrogen receptors and/or the aromatase enzyme [5–6, 8, 21, 47]. There may even be a secondary mechanism at work here which is related to trenbolone’s ability to downregulate expression in both the estrogen alpha and beta receptors [48].
There have been some other interesting discoveries with regard to the mechanisms behind trenbolone’s relationship with estrogen, as well as the compensatory responses associated with suppressed hormone levels. Trenbolone has been shown to reduce tissue concentrations, and gene expression, of VTG (vitellogenin) which is a protein positively associated with exposure to estrogenic compounds [13–14,21,41,47,49,50,51,52,53,54]. It has also been shown to downregulate brain CYP19B (aromatase B) and upregulate gonadal CYP19A (aromatase A) in female fish, but interestingly not in males [14,54].
Similar to what we’ve seen already in the HPG axis, the impacts of trenbolone on estrogen do not appear to be AR-dependent as trials have shown co-treatment with an AR antagonist (flutamide) resulted in the same anti-estrogenic activity in fish [13]. Interestingly, there has been another fish trial that reported trenbolone to have low-affinity with the estrogen receptor and can potentially even activate it [44]. Whether or not this is species-specific is a matter of debate, as I have not seen this occur in any other trials I’ve reviewed. However, cell culture experiments and bioassays do show that trenbolone and its metabolites have a very low binding affinity with estrogen receptors, roughly 20% of the efficacy of estradiol [40].
So can it aromatize? Although I have found nothing which definitively suggests it can, there has been a hypothesis thrown out there by Holland et al [55] which I find intriguing enough to include in its entirety:
“We previously reported that trenbolone enanthate potently reduced visceral fat mass in young and older ORX animals, indicating that fat loss occurs in response to androgen administration, even in the absence of an androgenic substrate for aromatase. However, our previous work did not account for the possibility that androstenedione (derived from dehydroepiandrosterone) can be aromatized to estrone and, subsequently, converted to E2 by actions of 17β-hydroxysteroid dehydrogenase in tissues, such as fat, expressing the required enzymes”
PROGESTERONE/SHBG
Trenbolone has been shown to have a high affinity for the bovine progestin receptor, and it is assumed that it has a similar affinity to the progesterone receptor as progesterone itself [56]. In vitro analysis has revealed that the relative binding affinity to the bovine progesterone receptor, as compared to progesterone, was 137.4% for 17β-TbOH and 2.1% for 17α-TbOH [57]. And finally, the relative binding affinity of trenbolone to human SHBG, as compared to DHT, is 29.4% for 17β-TbOH and 94.8% for 17α-TbOH.
VIII. Effects on Metabolic Health Markers
One of the primary reasons the anti-trenbolone crowd admonish against its use is related to how harsh the compound seemingly is on one’s health markers. I had hoped to have some actual reference blood work to add to this article, however unfortunately my crowdsourcing efforts were not successful as not many individuals run trenbolone by itself. So what I will do in this section is go over the available animal literature covering various health markers and trenbolone’s impacts upon them.
THYROIDAL AXIS
Arguably the most intriguing relationship to me is trenbolone and the thyroidal axis. Although the effects have been a bit inconsistent, there does seem to be a pattern which suggests trenbolone has an overall suppressive effect on the thyroidal axis. In one trial, trenbolone-alone decreased T4 in heifers while trenbolone plus estradiol decreased T4 in steers, while no impact was seen on T3 uptake [58]. In another trial, trenbolone plus estradiol actually increased T3 whereas trenbolone by itself decreased both T3 and T4 [59]. We must remember that estradiol stimulates the GH/IGF axis, which acutely increases the conversion of T4 to T3. This may help to explain why co-treatment with estradiol can result in higher T3 levels whereas trenbolone-only has the opposite effect, as estradiol levels are highly suppressed. Even in trials where thyroid levels are not significantly different, trenbolone decreased fasting metabolic rates, leading to less intake requirements for creating intake surplus [60].
Therefore, it may be reasonable to speculate the increased feed efficiency seen in numerous studies over the years could be related to trenbolone-mediated suppression of metabolic rate. Of course, it should be noted that leaner cattle just tend to grow faster, and use feed more efficiently, so it also may just be a byproduct of this [61]. Before I wrap this article series up, I’ll talk a bit more about the practical applications here and why these impacts may want to be considered when deciding how to use trenbolone for bodybuilding purposes.
CHOLESTEROL
Generally speaking, there is a strong correlation between fat loss and favorable changes in serum lipid levels, particularly in men [62–63]. Therefore, because trenbolone has been consistently shown to improve body composition, it is reasonable to speculate that it may have favorable impacts on lipid markers. So, let’s see what animal trials have shown us.
Studies on rats have shown that both testosterone and trenbolone elicit similar protections against elevated cholesterol despite trenbolone’s ability to elicit more visceral fat loss. This suggests that serum cholesterol levels may be governed primarily by overall body composition, independently of changes in visceral stores. In one trial, serum total cholesterol, HDL, and LDL were all significantly lower in trenbolone-treated intact rats than in control rats (- 62%, – 57%, and – 78% respectively). The byproduct of this was that treated rats had a greater HDL:LDL ratio. Serum triglycerides were also significantly decreased by 51% as compared to control rats [15]. In another trial, both testosterone and trenbolone reduced circulating cholesterol in rats fed a high fat and high sugar diet, but only trenbolone reduced circulating triglyceride levels [64].
It is strongly suggested to keep an eye on cholesterol levels when using supraphysiological doses of androgens, as they tend to have the ability to increase catecholamine-stimulated hormone-sensitive lipase (HSL) activity in both the liver and cardiac tissues [65–66]. This increased HSL activity tends to result in an increased rate of triglyceride breakdown and suppressed rates of HDL hydrolyzation. Having chronically suppressed levels of HDL seems to be an independent cardiovascular risk factor so prolonged use of androgens resulting in suppressed HDL levels should be done with extreme caution [67]
LIVER MARKERS
There are quite a few hepatic markers commonly used to assess overall liver functionality and health, as well as hepatic damage. Albumin is a marker indicative of overall liver function while AST, ALT, ALP are all general markers of hepatic damage.
Recent rodent trials have shown that trenbolone does not appear to induce significant damage to hepatic tissues. In one trial, hepatic tissue samples of trenbolone-treated rats showed a similar morphology to those of control rats. AST, ALT, ALP, and albumin were all at similar level in trenbolone-treated rats as compared to control [15]. In a follow-up trial, similar liver enzyme values were seen with rats fed high fat and high sugar diet in all treatment groups, including testosterone and trenbolone treatments [64].
INSULIN
This is another hormone that tends to have a direct correlation with body fat, and specifically visceral fat levels. Visceral fat accumulation and elevated circulating triglyceride levels are both associated with insulin resistance [68]. Conversely, calorie restriction and weight loss in viscerally obese non-diabetics induced significant improvements in insulin sensitivity [69]. In addition to obesity, there is also compelling evidence which shows that low androgen levels also promote insulin resistance [70]. It has been hypothesized that trenbolone treatment in animal models may promote insulin sensitizing effects through similar mechanisms to those achieved by calorie restriction in human males so let’s see what the trials have actually demonstrated.
One trial showed serum insulin to be significantly lower in trenbolone-treated rats (38% reduction) as compared to control rats which translated into a significantly lower HOMA-IR value, a metric used to measure insulin resistance [15]. Fascinatingly, rats being fed high fat and high sugar diets had significantly elevated serum insulin levels that were only partly restored with testosterone, yet trenbolone significantly reduced insulin levels [64]. In fact, trenbolone was also the only treatment group to reduce HOMA-IR values indicating increased beta-cell function and lowered insulin resistance. So albeit limited, the evidence does suggest that trenbolone has superior insulin sensitizing effects as compared to testosterone.
Adiponectin is a 30 kDa insulin sensitizing adipokine that is primarily secreted by visceral adipose tissues [71–72]. Generally speaking, serum adiponectin levels are inversely proportional to fat mass [73]. Testosterone and trenbolone tend to reduce total adiponectin levels to a similar degree in rats [74].
ERYTHROPOIESIS
Erythropoiesis is just a fancy term for the body’s production of red blood cells (RBCs). One of the most commonly reported side effects of TRT treatments tends to be elevated levels of hematocrit and hemoglobin. Specifically, androgen deprivation reduces both hematocrit and hemoglobin whereas testosterone administration results in a dose-dependent increase in both [75–76].
The mechanisms by which androgens augment RBC production may be directly related to stimulation of kidney erythropoietin secretion or even bone marrow [77]. And based upon existing evidence, it would appear as if androgens directly elevate erythropoiesis via AR-mediated mechanisms [11]. It does not appear as if the aromatization of testosterone is required for erythropoiesis as DHT administration also increases the process in male subjects [78]. Furthermore, it has also been demonstrated to occur in male subjects with aromatase-deficiencies [79]. Similarly, 5α reduction of testosterone does not appear to be required for erythropoiesis as the co-administration of testosterone and finasteride (5α reductase inhibitor) increased both hematocrit and hemoglobin to the same extent as testosterone alone despite 65% lower DHT concentrations in the finasteride group [80].
If trenbolone can reduce the elevations of hematocrit and hemoglobin seen with traditional TRT treatments, then this would be another potential reason it could be an interesting candidate for HRT. Let’s see what the trials indicate.
Preliminary evidence indicates that trenbolone increases hemoglobin in male rodents in a dose-dependent manner, and to a slightly greater extent than supraphysiological testosterone (8-10%), despite DHT being suppressed by over 70% following administration [20]. In another trial, at administered doses which were seven times higher than testosterone, trenbolone treated rats had nearly identical levels of hemoglobin, although both were significantly elevated as compared to controls [81].
Okay, I think this is a natural stopping point for part two. In part three, we’re going to begin to dive into the more exciting stuff as we cover anabolism and hypertrophy. Depending on how deeply we dive on the topic, it may be all we cover in part three. However, we also may cover lipolysis and some other fun topics if time permits. So, until next time…
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Link to part 3
The Science of Trenbolone, Part 3 Bodybuilding Steroid Profiles
In the last article, we covered a lot of ground, focusing primarily on the history of trenbolone as well as its metabolic fate in mammals. If you have not already read part one, I’d urge you to go back and give it a read before moving on, as some of the topics covered there will be expanded upon in this article.
VI. Effects on HPG Axis
In vertebrates, the hypothalamic-pituitary-gonadal (HPG) axis controls reproductive processes through a variety of hormones which act on target tissues either directly or indirectly. At a high level, in males, gonadotropin-releasing hormone (GnRH) released from the hypothalamus stimulates the pituitary to release luteinizing hormone (LH) and follicle stimulating hormone (FSH). These, in turn, stimulate the release of sex-hormones from the testes [1–2]. The strongly interwoven nature of the HPG axis means that no single component of the system operates in isolation. Upon entering circulation, both androgenic and estrogenic hormones are capable of crossing the blood-brain barrier and exerting negative feedback inhibition on the pituitary and hypothalamus, thereby downregulating GnRH release and suppressing the entire axis [3].
The administration of trenbolone is associated with numerous types of HPG axis disruptions, which is in line with what has been witnessed with various other androgen treatments over the years [4]. Some of the trenbolone-induced disruptions seen over the years include reduced levels of serum LH [5, 6, 7, 8, 9, 10], reduced serum FSH levels [11], reduced testosterone levels [5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16], reduced DHT levels [11], reduced estradiol levels [13,15], testicular atrophy [7,17–18], and a delayed onset of puberty [19]. These effects occur quite rapidly as, was demonstrated in one trial, within ten days of trenbolone enanthate administration, castrated rats had 80% suppression rates of serum testosterone and 70% suppression rates of DHT as compared to control animals [20]. It is worth noting, enanthate is a long ester variant of trenbolone (TBE) so the use of acetate (TBA) would have produced these effects even more rapidly.
It is not precisely understood what mechanisms are behind trenbolone’s suppressive effects on the HPG axis, however there have certainly been some trials over the years which provide clues. One popular hypothesis involves direct hypothalamic feedback inhibition, as evidenced by reduced GnRH transcription seen in the brains of fish models. This may be additive to its direct effects on testicular steroid biosynthesis, as supported by downregulated expression of testicular CYP17 [21]. CYP17 is a very important enzyme in steroid biosynthesis, and sequentially catalyzes two key reactions in the production of sex steroids in males.
It is also interesting to note that whatever the mechanism is, it does not appear to be androgen receptor (AR) dependent [22–23]. Further supporting this line of thought, in ovary tissue cultures from fish, non-aromatizable androgens such as trenbolone had direct and non-genomic, anti-androgen-insensitive inhibitory, effects on estrogen production [24]. It is highly likely that the underlying feedback mechanisms at work are similar to other androgens, resulting in inhibited GnRH levels and ultimately inhibited FSH and LH production [25].
One other potential gene candidate involved in decreased sex steroid concentrations, noted in fish trials in which they had been exposed to the strong exogenous androgen 17-trenbolone, is hydroxysteroid (17β) dehydrogenase 12a (hsd17b12a). Hsd17b12a catalyzes the conversion of androstenedione to testosterone which, in turn, is converted to 17β-estradiol by the aromatase enzymes. Thus, down-regulation of hsd17b12a, as seen in these trenbolone-exposed fish, is predictably expected to lead to declines in both testosterone and estradiol [14].
VII. Effects on Anabolic Pathways
As we’ve covered previously, trenbolone expresses SARM-like behaviors and I’d like to use this section to discuss them in more depth.
5α REDUCTASE
Despite a structural similarity to testosterone, trenbolone does not undergo 5α reduction due to the presence of a 3-oxotriene structure which prevents A ring reduction [26]. This is the pathway used for converting testosterone into its more potent form dihydrotestosterone (DHT). As trenbolone is not a substrate for 5α reductase, it has been shown to stimulate less pronounced androgenic effects than testosterone in androgen-sensitive tissues which express the 5α reductase enzyme, including the prostate and accessory sex organs [27, 28, 29. 30. 31, 32]. To put this statement into perspective, testosterone has an approximately three-fold higher potency in androgenic tissues that express 5α reductase despite having a significantly lower binding affinity to the AR than trenbolone [33]. We’ll discuss how this impacts hypertrophy potential in these tissues a bit later.
As you can already start to imagine, one particular reason trenbolone is beginning to pick up steam in scientific communities is due to its potential to lower the risks associated with prostate cancer in those patients being treated for hypogonadism. The current de facto treatment strategy for these individuals includes providing them with testosterone, in a manner designed to restore hormone levels to natural reference ranges. However, in adult males, benign and malignant growth of the glandular prostate tissue is largely regulated by sex hormones. And furthermore even moderate increases in circulating testosterone have been shown to directly translate into pronounced hyperplastic effects in prostate tissues, mediated via its 5α reduction into DHT [34–35]. Later in the article, we’ll dig deeper into the available literature to see if trenbolone’s potential to lower prostate cancer risk actually pans out.
AROMATASE ENZYME
Seemingly one of the more asked about questions is whether or not trenbolone has impacts on serum estrogen levels, as well as whether or not it can aromatize like testosterone. Popular opinion in the scientific community is that trenbolone and other 19-nor compounds are not substrates for the aromatase enzyme [36–37]. With that said, please understand this is not the same thing as saying they cannot convert to estrogen as C19 norandrogens can induce estrogenic effects [38–39].
Following this line of thought, trenbolone-itself is largely thought to be non-estrogenic [40–41] and there have been numerous animal trials that have demonstrated it reduces serum estradiol concentrations [13, 14, 15, 42, 43, 44]. Keep in mind that there have been a few trials that did not show this suppressive effect on estrogen levels [10,45–46] but, by and large, the body of literature as a whole does support the hypothesis that trenbolone possesses anti-estrogenic effects.
Based upon what we now know about the HPG axis, this would tend to make a lot of sense as the anti-estrogenic effects caused by trenbolone administration likely have to do with its negative feedback on the axis. This negative feedback would cause the inhibition of endogenous testosterone production, thereby leading to suppressed levels of aromatization via the aromatase enzyme, which is necessary for endogenous estrogen biosynthesis in males. This impact on the HPG axis would cause a more severe rate of estrogen inhibition as compared to any potential direct effects trenbolone would have on estrogen receptors and/or the aromatase enzyme [5–6, 8, 21, 47]. There may even be a secondary mechanism at work here which is related to trenbolone’s ability to downregulate expression in both the estrogen alpha and beta receptors [48].
There have been some other interesting discoveries with regard to the mechanisms behind trenbolone’s relationship with estrogen, as well as the compensatory responses associated with suppressed hormone levels. Trenbolone has been shown to reduce tissue concentrations, and gene expression, of VTG (vitellogenin) which is a protein positively associated with exposure to estrogenic compounds [13–14,21,41,47,49,50,51,52,53,54]. It has also been shown to downregulate brain CYP19B (aromatase B) and upregulate gonadal CYP19A (aromatase A) in female fish, but interestingly not in males [14,54].
Similar to what we’ve seen already in the HPG axis, the impacts of trenbolone on estrogen do not appear to be AR-dependent as trials have shown co-treatment with an AR antagonist (flutamide) resulted in the same anti-estrogenic activity in fish [13]. Interestingly, there has been another fish trial that reported trenbolone to have low-affinity with the estrogen receptor and can potentially even activate it [44]. Whether or not this is species-specific is a matter of debate, as I have not seen this occur in any other trials I’ve reviewed. However, cell culture experiments and bioassays do show that trenbolone and its metabolites have a very low binding affinity with estrogen receptors, roughly 20% of the efficacy of estradiol [40].
So can it aromatize? Although I have found nothing which definitively suggests it can, there has been a hypothesis thrown out there by Holland et al [55] which I find intriguing enough to include in its entirety:
“We previously reported that trenbolone enanthate potently reduced visceral fat mass in young and older ORX animals, indicating that fat loss occurs in response to androgen administration, even in the absence of an androgenic substrate for aromatase. However, our previous work did not account for the possibility that androstenedione (derived from dehydroepiandrosterone) can be aromatized to estrone and, subsequently, converted to E2 by actions of 17β-hydroxysteroid dehydrogenase in tissues, such as fat, expressing the required enzymes”
PROGESTERONE/SHBG
Trenbolone has been shown to have a high affinity for the bovine progestin receptor, and it is assumed that it has a similar affinity to the progesterone receptor as progesterone itself [56]. In vitro analysis has revealed that the relative binding affinity to the bovine progesterone receptor, as compared to progesterone, was 137.4% for 17β-TbOH and 2.1% for 17α-TbOH [57]. And finally, the relative binding affinity of trenbolone to human SHBG, as compared to DHT, is 29.4% for 17β-TbOH and 94.8% for 17α-TbOH.
VIII. Effects on Metabolic Health Markers
One of the primary reasons the anti-trenbolone crowd admonish against its use is related to how harsh the compound seemingly is on one’s health markers. I had hoped to have some actual reference blood work to add to this article, however unfortunately my crowdsourcing efforts were not successful as not many individuals run trenbolone by itself. So what I will do in this section is go over the available animal literature covering various health markers and trenbolone’s impacts upon them.
THYROIDAL AXIS
Arguably the most intriguing relationship to me is trenbolone and the thyroidal axis. Although the effects have been a bit inconsistent, there does seem to be a pattern which suggests trenbolone has an overall suppressive effect on the thyroidal axis. In one trial, trenbolone-alone decreased T4 in heifers while trenbolone plus estradiol decreased T4 in steers, while no impact was seen on T3 uptake [58]. In another trial, trenbolone plus estradiol actually increased T3 whereas trenbolone by itself decreased both T3 and T4 [59]. We must remember that estradiol stimulates the GH/IGF axis, which acutely increases the conversion of T4 to T3. This may help to explain why co-treatment with estradiol can result in higher T3 levels whereas trenbolone-only has the opposite effect, as estradiol levels are highly suppressed. Even in trials where thyroid levels are not significantly different, trenbolone decreased fasting metabolic rates, leading to less intake requirements for creating intake surplus [60].
Therefore, it may be reasonable to speculate the increased feed efficiency seen in numerous studies over the years could be related to trenbolone-mediated suppression of metabolic rate. Of course, it should be noted that leaner cattle just tend to grow faster, and use feed more efficiently, so it also may just be a byproduct of this [61]. Before I wrap this article series up, I’ll talk a bit more about the practical applications here and why these impacts may want to be considered when deciding how to use trenbolone for bodybuilding purposes.
CHOLESTEROL
Generally speaking, there is a strong correlation between fat loss and favorable changes in serum lipid levels, particularly in men [62–63]. Therefore, because trenbolone has been consistently shown to improve body composition, it is reasonable to speculate that it may have favorable impacts on lipid markers. So, let’s see what animal trials have shown us.
Studies on rats have shown that both testosterone and trenbolone elicit similar protections against elevated cholesterol despite trenbolone’s ability to elicit more visceral fat loss. This suggests that serum cholesterol levels may be governed primarily by overall body composition, independently of changes in visceral stores. In one trial, serum total cholesterol, HDL, and LDL were all significantly lower in trenbolone-treated intact rats than in control rats (- 62%, – 57%, and – 78% respectively). The byproduct of this was that treated rats had a greater HDL:LDL ratio. Serum triglycerides were also significantly decreased by 51% as compared to control rats [15]. In another trial, both testosterone and trenbolone reduced circulating cholesterol in rats fed a high fat and high sugar diet, but only trenbolone reduced circulating triglyceride levels [64].
It is strongly suggested to keep an eye on cholesterol levels when using supraphysiological doses of androgens, as they tend to have the ability to increase catecholamine-stimulated hormone-sensitive lipase (HSL) activity in both the liver and cardiac tissues [65–66]. This increased HSL activity tends to result in an increased rate of triglyceride breakdown and suppressed rates of HDL hydrolyzation. Having chronically suppressed levels of HDL seems to be an independent cardiovascular risk factor so prolonged use of androgens resulting in suppressed HDL levels should be done with extreme caution [67]
LIVER MARKERS
There are quite a few hepatic markers commonly used to assess overall liver functionality and health, as well as hepatic damage. Albumin is a marker indicative of overall liver function while AST, ALT, ALP are all general markers of hepatic damage.
Recent rodent trials have shown that trenbolone does not appear to induce significant damage to hepatic tissues. In one trial, hepatic tissue samples of trenbolone-treated rats showed a similar morphology to those of control rats. AST, ALT, ALP, and albumin were all at similar level in trenbolone-treated rats as compared to control [15]. In a follow-up trial, similar liver enzyme values were seen with rats fed high fat and high sugar diet in all treatment groups, including testosterone and trenbolone treatments [64].
INSULIN
This is another hormone that tends to have a direct correlation with body fat, and specifically visceral fat levels. Visceral fat accumulation and elevated circulating triglyceride levels are both associated with insulin resistance [68]. Conversely, calorie restriction and weight loss in viscerally obese non-diabetics induced significant improvements in insulin sensitivity [69]. In addition to obesity, there is also compelling evidence which shows that low androgen levels also promote insulin resistance [70]. It has been hypothesized that trenbolone treatment in animal models may promote insulin sensitizing effects through similar mechanisms to those achieved by calorie restriction in human males so let’s see what the trials have actually demonstrated.
One trial showed serum insulin to be significantly lower in trenbolone-treated rats (38% reduction) as compared to control rats which translated into a significantly lower HOMA-IR value, a metric used to measure insulin resistance [15]. Fascinatingly, rats being fed high fat and high sugar diets had significantly elevated serum insulin levels that were only partly restored with testosterone, yet trenbolone significantly reduced insulin levels [64]. In fact, trenbolone was also the only treatment group to reduce HOMA-IR values indicating increased beta-cell function and lowered insulin resistance. So albeit limited, the evidence does suggest that trenbolone has superior insulin sensitizing effects as compared to testosterone.
Adiponectin is a 30 kDa insulin sensitizing adipokine that is primarily secreted by visceral adipose tissues [71–72]. Generally speaking, serum adiponectin levels are inversely proportional to fat mass [73]. Testosterone and trenbolone tend to reduce total adiponectin levels to a similar degree in rats [74].
ERYTHROPOIESIS
Erythropoiesis is just a fancy term for the body’s production of red blood cells (RBCs). One of the most commonly reported side effects of TRT treatments tends to be elevated levels of hematocrit and hemoglobin. Specifically, androgen deprivation reduces both hematocrit and hemoglobin whereas testosterone administration results in a dose-dependent increase in both [75–76].
The mechanisms by which androgens augment RBC production may be directly related to stimulation of kidney erythropoietin secretion or even bone marrow [77]. And based upon existing evidence, it would appear as if androgens directly elevate erythropoiesis via AR-mediated mechanisms [11]. It does not appear as if the aromatization of testosterone is required for erythropoiesis as DHT administration also increases the process in male subjects [78]. Furthermore, it has also been demonstrated to occur in male subjects with aromatase-deficiencies [79]. Similarly, 5α reduction of testosterone does not appear to be required for erythropoiesis as the co-administration of testosterone and finasteride (5α reductase inhibitor) increased both hematocrit and hemoglobin to the same extent as testosterone alone despite 65% lower DHT concentrations in the finasteride group [80].
If trenbolone can reduce the elevations of hematocrit and hemoglobin seen with traditional TRT treatments, then this would be another potential reason it could be an interesting candidate for HRT. Let’s see what the trials indicate.
Preliminary evidence indicates that trenbolone increases hemoglobin in male rodents in a dose-dependent manner, and to a slightly greater extent than supraphysiological testosterone (8-10%), despite DHT being suppressed by over 70% following administration [20]. In another trial, at administered doses which were seven times higher than testosterone, trenbolone treated rats had nearly identical levels of hemoglobin, although both were significantly elevated as compared to controls [81].
Okay, I think this is a natural stopping point for part two. In part three, we’re going to begin to dive into the more exciting stuff as we cover anabolism and hypertrophy. Depending on how deeply we dive on the topic, it may be all we cover in part three. However, we also may cover lipolysis and some other fun topics if time permits. So, until next time…
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