The Science of Trenbolone, Part 3

We are going to dig more into trenbolone’s anabolic properties in this part of the article series. It is worth reiterating that all studies relevant to today’s topics were performed on animals. So, my goal is to cover what is available within the literature and begin to discuss what is relevant to us, as bodybuilders. Many of the underlying mechanisms are going to be similar between mammals, and I will do my best to point out when this isn’t the case.

IX. Anabolism

Before we get into the studies, it is important to point out that there are differences between humans and the animals most commonly used in trenbolone studies (e.g. sheep, mice, cows, etc). As we dive deeper into the studies, I’d like for us to all keep these differences in mind, as they can certainly impact the relevancy to humans.

Most rodent skeletal muscle possesses a very low percentage of AR positive nuclei. An example is the extensor digitorum longus, located near the front of the leg, with only 7% AR positive myonuclei [1]. This is not universally true, as the levator ani/bulbocavernosus (LABC) muscle complex (located near the pelvis) contains 70-75% AR-positive myonuclei and experiences robust myotropic response to androgen administration [2,3,4]. So, if you are comparing multiple rodent studies, and they used combinations of these muscles in the trial, then you can likely expect a wide disparity in results.

Conversely, cattle are generally highly sensitive to androgen-induced stimuli due to high concentrations of ARs in bovine skeletal muscle and satellite cells [5,6,7]. We’ll need to further understand that bulls are mature, and intact, males whereas steers are males that have been castrated before reaching sexual maturity. The vast majority of trials are going to be performed on steers as implantation of trenbolone does relatively nothing to intact bulls. They are likely already at their maximum growth potential with their elevated endogenous hormone levels, however combined TBA/E2 implants are necessary to produce maximum growth and feed efficiency in castrated steers [8]. Heifers are young females that have never calved; they are also used on occasion for implantation trials.

Intact bulls produce very high levels of testosterone. In addition to having a very poor response to implantation, they also generally have larger muscle fibers than steers [9]. Bulls also tend to have a higher percentage of fast-twitch oxidative-glycolytic fibers combined with a lower percentage of fast-twitch glycolytic fibers in the longissimus dorsi (LD) muscles than steers have [10]. It is for these reasons that bulls produce higher total carcass yields but they are generally lower quality grade. Castrated steers tend to have more external fat and marbling however they are offset by a decreased rate of weight gain and lower feed efficiency. So in the quest for higher yields with higher quality meat, researchers began to investigate anabolic implants to see if they can produce the best of both worlds.

Lastly, a quick little side-note – humans are quite similar to cows in that we also respond robustly to androgenic stimuli due to the high percentages of AR-positive myonuclei [11].

Androgen Receptor Affinity

Trenbolone has been shown to bind with both the human AR, as well as ARs of various other species, with approximately three times the affinity than testosterone, or approximately equal to that of DHT [12,13,14,15,16]. In human ARs, the active metabolite 17β-TbOH showed a 109% binding affinity as compared to DHT, with the inactive metabolite 17α-TbOH coming in at 4.5% [13]. With this said, receptor binding studies should be seen as a cheap and rapid tool for an initial evaluation of a ligand, not factoring in things such as subsequent initiation of gene transcription, etc. In other words, because trenbolone binds with a three times higher affinity than testosterone to the AR, this does not literally mean it will produce three times the hypertrophy.

Furthering this point, in comparison trials, trenbolone was shown to produce either equal or slightly greater growth in the LABC muscle complex as compared to testosterone [14,17,18,19,20,21,22]. The LABC is an androgen responsive tissue which lacks the 5α reductase enzymes. Whereas testosterone exerts enhanced effects in tissues expressing 5α reductase, trenbolone exerts equal effects in those tissues versus those that do not which produces a favorable anabolic:androgenic ratio compared to testosterone [23]. We’ll go more into this when we discuss prostate cancer risks later in the article series.

X. Hypertrophy

I had originally planned to do a very deep-dive into the mechanisms behind hypertrophy however I think that may be better done in its own article as it is a very complex topic. I will still need to cover the foundational elements of hypertrophy though, or else a lot of this topic may be more confusing than it needs to be. So therefore, I will not be diving too deeply in intracellular signaling pathways, as this would take this article and make it unnecessarily inflated. If there is enough interest, perhaps an article on that topic can be a future project.

Hypertrophy Fundamentals

Before we get into the studies, let’s talk a little about what hypertrophy is and how it occurs in mammals. Again, this is going to be more of a high-level pass at the topic but hopefully deep enough that the terms used later will be better understood.

The number of muscle fibers in mammals is essentially fixed at birth, so postnatal muscle growth must result from the hypertrophy of existing muscle fibers. This fiber hypertrophy requires an increase in the number of myonuclei present within these fibers; however the nuclei present in muscle fibers are unable to divide, so the nuclei must come from outside the fiber [24]. The source of the nuclei needed to support fiber hypertrophy happen to be a group of mononucleated myogenic cells (satellite cells) located between the basal lamina and the plasma membrane (sarcolemma) of muscle fibers [25]. There is a strong correlation between rates of postnatal growth and the rates at which satellite cells accumulate within muscle tissues. This would seemingly make sense as there will be more overall machinery available to fuel the hypertrophy process [26].

These muscle satellite cells play a crucial role in postnatal muscle growth by fusing with existing muscle fibers, providing the nuclei required for postnatal fiber growth. In newborn animals, a much higher percentage of muscle nuclei are satellite cells, but this percentage significantly decreases with age [27]. Not only is there a reduction in satellite cell numbers, but those cells still present withdraw from the proliferative state of the cell cycle and enter a state of quiescence, which consequently leads to a growth plateau. So finding ways to overcome these physiological limitations can hypothetically lead to superior postnatal growth rates.

To ensure there are adequate numbers of usable satellite cells, they first must be activated which will allow them to progress through the cell cycle and ultimately contribute DNA to the existing muscle fiber. After these dormant satellite cells have been activated, there is subsequently a need for growth factors capable of stimulating satellite cell proliferation and differentiation. Both IGF-1 and fibroblast growth factor-2 (FGF-2) are examples of potent stimulators of satellite cell proliferation [28–29]. IGF-I is unique in that it promotes muscle cell differentiation in skeletal muscle, whereas FGF-2 inhibits differentiation [30]. I’ll talk more about the relationship between trenbolone and IGF-1 a bit later in the article.

So taking a slight step backward, when a hypertrophy activation event occurs (e.g. exercise or muscle damage) it leads to satellite cell proliferation. This satellite cell proliferation causes them to fuse with existing muscle fibers, providing new nuclei for hypertrophy and repair, and to support ramped-up protein synthesis. An overly-simplified way to think about this – satellite cells can be activated to proliferate (divide) and donate their DNA (nuclei) to the existing muscle fiber (differentiation).

This donated DNA leads muscle fibers to form the fusion of myoblasts (proliferating cells) into multinucleated muscle fibers called myotubes. These myotubes may fuse to existing myofibers, or even each other, directly generating new muscle fibers. This is about as deeply as I want to take this topic for now.

Growth Promoting Effects

The growth promoting effects of trenbolone are well-known and have been studied by researchers for decades. The goal has always been to find ways to promote greater meat yields along with a higher quality finished product. We’ll focus primarily on the meat yields for now, as the quality of meat often tends to coincide with the amount of intramuscular fat content. This falls more into the realm of lipolysis, which we’ll be covering later in this article series.

Trenbolone has been shown to increase total body growth and skeletal muscle mass in various animal trials when administered alone [3, 14, 17, 19, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44], in combination with estradiol [45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66], in combination with testosterone and estradiol [67], as well as in combination with estradiol plus growth hormone [68]. This hypertrophy potential is pretty much universally observed, and crosses many different administration methods as well as species of animals.

Interestingly, numerous studies have shown that a combined TBA/E2 implant is more effective than either TBA or E2 alone in stimulating the growth of feedlot steers [8, 45, 52, 54–55, 69, 70, 71, 72, 73, 74]. The hypothesis that estradiol enhances the anabolic effects of trenbolone has been floating around as far back as the 1970s [75–76]. Potentially even more interesting is that the combined treatment increases hypertrophy potential despite the fact that it results in serum trenbolone levels which are actually lower, by roughly half [8].

One of the reasons I suspect this to be the case, particularly in steers, is that implantation with trenbolone suppresses endogenous estradiol levels due to its impacts on the HPG axis. Estrogen and, more specifically, aromatase activity is a potent stimulator of the GH/IGF axis. Supporting this hypothesis, implantation with trenbolone-only has been shown to lower, serum GH levels [8,68,69,70,71]. Conversely, steers implanted with E2 alone have been shown to have increased circulating concentrations of both GH and IGF-1 [77–78]. These combined TBA/E2 implants likely result in increased GH levels, and may even alter the number and/or affinity of GHRs in tissues such as the liver [79]. As we learned earlier, having adequate growth factors to stimulate satellite cell proliferation and differentiation is a crucial step in the hypertrophy process.

Optimal TBA / E2 Ratios

Since combined treatments seem to have enhanced anabolic characteristics, many trials over the years have attempted to answer the question what is the optimal TBA/E2 ratio for eliciting maximal growth ratio? There have been some that proclaim the answer lies somewhere between 5:1 and 8:1 [52,54] however results have varied quite a bit over the years. In fact, in one trial, average daily growth rates (ADG) were quite similar in steers implanted with either 25mg E2, 120mg TBA, or a combined 120mg TBA + 24mg E2 implant [80].

Another trial demonstrated that 120mg TBA + 24mg E2 increased average rates of gain by 20-25% and feed efficiency by 15-20% [55]. In fact, it has been shown that combined treatments lead to 50% more actively proliferating satellite cells from the semimembranosus muscle (hamstring) of control steers [81]. As you recall from earlier, the proliferation of satellite cells is a crucial step in the hypertrophy process. Other trials have similarly shown a trenbolone-induced increase in both satellite cell activation and proliferation [82–83]. It appears that trenbolone and testosterone increase satellite cell numbers per muscle fiber to a similar degree [22] so this is not a unique effect of trenbolone. Its effects on satellite cells may be, at least partially, mediated via the IGF-1 receptor as inhibition of several downstream targets of IGF-1 (e.g. MAPK, MEK/ERK, PI3K/Akt) suppressed trenbolone-induced satellite cell proliferation in cell cultures [7].

In 2007 the FDA approved Revalor-XS which is 200mg of TBA + 40mg of E2, designed to have a delayed release of hormones due to a specialized polymer coating on six of the ten pellets in the pack. This is beneficial as traditional implant methods require multiple implants having the potential to add stress which could negatively affect cattle performance. Much of the variation in trial results over the years could very well be related to this. Trials investigating Revalor-XS have found that the higher dose of TBA/E2 improved steer performance when steers are on feed for longer periods [65,140]. Despite the speculation that multiple implants can cause added stress to steers, the delayed release pattern of Revalor-XS did not actually provide any unique effects on steer performance, or quality grade, when compared with a reimplantation strategy of an equal TBA + E2 dose.

Effects of IGF-1

TBA/E2 implants have been shown to significantly increase IGF-1 levels. These combined treatments have resulted in increased serum IGF-1 levels [59,84,85,86], increased hepatic IGF-1 mRNA expression [56], and increased IGF-1 mRNA expression in skeletal muscle tissues [59,61,81].

TBA-only implants have also been shown to increase IGF-1 levels in various species, however not nearly to the degree of combined implants [87,88,89]. In fact, trenbolone does not significantly increase either autocrine or endocrine IGF-1 in a manner greater than testosterone. One trial even demonstrated that testosterone increases autocrine IGF-1 levels slightly higher than TBA [4]. Evidence seems to suggest that any effects on IGF-1 may be mediated via estradiol, and may even be stimulated via distinct androgen and estrogen receptor mechanisms, which include involvement of the G-protein-coupled receptor (GPR30) [90]. One trial in particular found that increased autocrine expression of IGF-1 in skeletal muscle requires estrogen, and TBA-only implants resulted in no increases in muscle IGF-1 mRNA levels [91]. It is certainly reasonable to speculate that there may be a threshold that must be met, which may not be realistic to see in animal trials. Let’s move along to cell studies to see if this hypothesis pans out.

In vitro studies using bovine satellite cells (BSCs) showed a dose-dependent relationship between trenbolone and IGF-1 mRNA levels. In the cells treated with 1nM or 10nM of trenbolone for 48 hours, IGF-1 mRNA levels were 1.7 times higher, however mRNA levels were not affected by treatments of 0.001, 0.01, or 0.1nM [92]. It also appeared that the effects were at least partially mediated via the AR as co-treatment with flutamide (AR inhibitor) completely negated the increased IGF-1 expression seen in these cultures [90].

It does not take much time at all to see increased levels of IGF-1 after an implantation. In one trial, lambs implanted with Revalor-S (120mg TBA / 24mg E2) showed increased serum IGF-1 levels by day 3 and day 10 of 43% and 62% respectively [56]. This increased IGF-1 was maintained for the entire 24 days of the study and steady state hepatic IGF-1 mRNA levels were 150% higher in implanted lambs than in controls, suggesting the liver is likely a primary source of the increased circulating IGF-1. Autocrine IGF-1 mRNA levels were also 68% higher in the longissimus muscles of implanted lambs than were seen in controls. The dosage of TBA and E2, per kilogram of body weight, was approximately three times higher than that approved for use in steers though. Because of the species and dosage differences, caution should be used when trying to take these results and apply them to steers.

Using this same dose in steers has been shown to produce higher serum IGF-1 levels as compared to non-implanted cattle, within 6-42 days of implantation [93]. Within only 48 hours, implanted steers had a 13.4% increase in serum IGF-1 concentrations [84]. On days 21 and 40, implanted steers had 16% and 22% higher IGF-1 levels as compared to controls. Now where it gets interesting is that IGF-1 levels peaked during this timeframe and subsequently began falling through day 115 of the study where they ended up similar to day 1 values. With that said, control steers still had lower IGF-1 levels than day one. So although the increases in IGF-1 levels appear transient, implants still seem to provide an overall additive effect, even with long-term use.

Other trials on cattle have shown muscle samples with higher IGF-1 mRNA within 30-40 days of implantation [56,61]. These implanted animals also showed more proliferating satellite cells than non-implanted steers suggesting TBA/E2-induced increases in muscle IGF-I may be at least partially responsible for the muscle growth observed in implanted steers. As we discussed earlier, it is well established that postnatal muscle growth depends on fusion of satellite cells with existing fibers to provide myonuclei necessary to support growth [24]. This increase is also important because only a small number of satellite cells are present at this time in yearling cattle, and many of the existing cells have become quiescent or left the cell cycle. It is also worth mentioning that IGF-1 overexpression extends the replicative lifespan of satellite cells, at least in cell cultures [94]. Therefore, it seems reasonable to hypothesize that increased muscle IGF-I expression plays a role in the AAS-induced increase in muscle satellite cell numbers.

In another trial, hepatic steady state IGF-1 mRNA levels were shown to be 69% higher in implanted steers, again suggesting that the liver may be a large contributing factor to increased circulating IGF-1 in implanted animals [61]. Please note that there has been at least one study, which I’m aware of, to show no differences in IGF-1 concentrations between implanted steers and control cattle [95]. This would tend to be the exception and not the rule, however.

An androgen response element (ARE) has been identified in the promoter region of the IGF-I gene, suggesting that the androgen receptor-ligand complex may interact with this ARE to stimulate transcription of the IGF-I gene. Androgens tend to act via multiple mechanisms on muscle though, and estrogen tends to act on the hypothalamus/anterior pituitary to stimulate GH/IGF axis [96]. The relationship between estrogen and the GH/IGF axis has been shown to be additive [97–98].

Estrogen Primer

Since we are kind of heading this direction anyway, let’s take a brief moment to focus our attention more on estrogen before moving forward.

In vitro studies have shown that treatment of bovine satellite cell cultures for 48 hours with E2 significantly increases IGF-1 mRNA expression [92]. This is in line with what we already know about E2, as it has been shown to stimulate expression of IGF-1 mRNA in a number of tissues [99–100]. Interestingly enough, co-treatment with ICI (estrogen receptor antagonist) did not suppress this E2-stimulated IGF-1 expression. This seems to suggest that the mechanism by which E2 stimulates IGF-I mRNA expression in BSCs may be different than the mechanism acting in other tissues which have been examined to date.

Even though the IGF-I gene does not contain a traditional estrogen response element (ERE) in its regulatory region, E2-stimulation of IGF-I mRNA expression can occur via a pathway involving the AP-1 enhancer [101]. As mentioned previously, in addition to the classical estrogen receptors, G-protein-coupled receptor 30 (GRP30) may play a role in mediating the actions of estrogen [102,103,104]. This is relevant to our interests as muscle tissue contains GPR30 mRNA and immunohistochemical studies have localized GPR30 receptor protein within skeletal muscle cells [105]. Furthermore, the effects of GPR agonist/antagonist strongly indicate the GPR30 receptor is involved in the E2-stimulated increase in IGF-1 mRNA observed in bovine satellite cell cultures [90].

Effects on Muscle Fibers

Implantation with TBA/E2 increases the cross-sectional area (CSA) of muscle fibers due to an initial increase in DNA transcription followed by an increase in nuclei within the muscle fiber which support hypertrophy [106]. TBA (either alone or in combination with E2) has traditionally been shown to increase the CSA of type I but not type II muscle fibers [9,107]. Combined implantation of feedlot steers has also been shown to increase type I and IIA CSA in LM muscles [110]. There have been exceptions, as one trial has been shown to increase type IIB fibers without any impact on the size or number of type I fibers [57]. These trials, when taken as a whole, seem to suggest that trenbolone induces a fiber switch from more glycolytic to more oxidative fibers, which indicates an increase in the oxidative capacity of the skeletal muscle fibers.

Getting back to the potential differences seen in species, despite the increase in muscle weight and muscle fiber size, the number of myonuclei per fiber was not enhanced with rats being administered either trenbolone or testosterone [22]. This contradicts the results from an earlier trial, however testosterone was administered beginning at the onset of puberty which is a rapid growth phase for the LABC muscle versus the more mature muscles in the previous study [108]. It is highly likely that androgen-induced hypertrophy in adult rats without exercise stimulus may not require myonuclear addition [109], which kind of goes against the grain of what we’ve been talking about the entire article. But these are also exactly the types of things to keep an eye out for when looking over animal trials and trying to establish patterns which may be potentially translated to humans.

Effects of Androgen Receptors

There have been multiple in vitro experiments that indicate trenbolone upregulates AR mRNA expression [111–112]. There does appear to be a ceiling effect though, where higher doses fail to alter mRNA levels to a degree relative to those present in untreated control cultures [92].

This has not universally been demonstrated in trials however, as some have shown no trenbolone-mediated effects upon AR mRNA expression [4,91]. This discrepancy may be because the elevated AR expression occurs at an earlier time point than data collection was taken in these trials, but that is speculative. In vitro evidence also indicates trenbolone induces translocation of human ARs to the cell nucleus in a dose-dependent manner, and it also stimulates gene transcription to at least the same degree as DHT [14].

XI. Atrophy / Anti-Catabolism

Trenbolone’s reputation as a muscle-preserving hormone is actually well deserved. I would like to briefly go over the basics of skeletal muscle atrophy before diving into the literature associated with trenbolone-specifically.

During various catabolic states, the ubiquitin-proteasome pathway increases protein breakdown leading to skeletal muscle atrophy. Specifically two ubiquitin ligases, MuRF1 and MAFbx (also called Atrogin-1) serve as markers of skeletal muscle atrophy under these various catabolic states such as fasting, cancer, renal failure, and diabetes [113,114,115]. Trenbolone has been shown to significantly decrease MuRF1 and atrogin-1 mRNA expression in the skeletal muscle tissues by a factor of 3 in castrated rats. Atrogin-1 rates were suppressed in these animals to an even greater degree than testosterone administration [4].

Glucocorticoids

Glucocorticoids are steroid hormones which help regulate whole-body metabolic homeostasis. They also exert their influence on skeletal muscle with elevated exposure to them potentially leading to atrophy of tissues. The major members of the glucocorticoid family are cortisol, corticosterone, and cortisone. They bind with the intracellular glucocorticoid receptor (GR) where they activate and exert their effects. It is worth mentioning that cortisol can bind to both the GR and mineralocorticoid receptor (MR), however a deep dive on this is beyond the scope of this article series.

Trenbolone has been shown to lower glucocorticoid binding capacity by causing a decreased number of GRs in skeletal muscle tissues [36,116]. In vitro studies have demonstrated trenbolone to act as a glucocorticoid receptor antagonist [14] despite 17β-TbOH possessing only a 9.4% relative binding affinity to the bovine glucocorticoid receptor as compared to cortisol [13]. Other studies have shown that trenbolone reduces the ability of cortisol to bind to skeletal muscle GRs as well as downregulating overall GR expression [117–118]. In fact, trenbolone suppresses GR expression 50% more than testosterone [4]. And its anti-glucocorticoid actions likely help it produce a significantly more robust inhibition of muscle protein breakdown (MPB) than testosterone, which only slightly reduces MPB while simultaneously increasing MPS [119].

Trenbolone has been shown to reduce circulating corticosterone concentrations in rodents [37,39,116,120] as well as cortisol in implanted cattle [50]. Evidence suggests that trenbolone works in the adrenals to suppress ACTH-stimulated cortisol synthesis as well as suppressing cortisol release [121].

We may now try and extrapolate a bit further on what these lowered glucocorticoid levels may do. For example, glucocorticoids inhibit glucose uptake and help stimulate glycogen breakdown in skeletal muscle by attenuating insulin-induced GLUT4 translocation to the cell membranes [122]. Insulin signaling in muscle tissues is essentially suppressed by glucocorticoids [123]. With this said, is it possible that trenbolone administration could create an environment of enhanced glucose utilization? We’ve already seen its ability to increase insulin sensitivity in rat models, what if one were to run it alongside exogenous insulin?

Glucocorticoids also tend to increase intramuscular triglyceride levels [124]. Is it thereby reasonable to speculate that the cosmetic effects traditionally attributed to trenbolone may have something to do with this? If trenbolone is reducing intramuscular triglyceride levels, then could this be a primary factor behind why many tend to have drier looking muscles? I’ll circle back to some of these questions in my closing remarks of the article series.

Effects on Protein Synthesis and Breakdown

One of the more amusing bits of information on trenbolone is that the rate of muscle protein synthesis (MPS) actually decreases with administration. This has been demonstrated in trials with either TBA implants or TBA+E2 implants [17,32,48]. Many folks hear this and wonder how trenbolone can be such a potent anabolic when it reduces MPS rates? The key here goes back to trenbolone’s impacts on MPB, as it is very adept at lowering rates of MPB to a greater degree than MPS, which results in a net-anabolic state.

In fact, despite lowering rates of MPS, trenbolone has been shown to increase whole body nitrogen retention in various species [32,125,126,127]. Again, this has a lot to do with trenbolone’s impacts on MPB rates. It has been shown to cause significantly decreased rates of total and myofibrillar MPB in various species [32,34,36,120,128].

It is worth noting that in vitro studies have actually shown trenbolone-induced concentration-dependent increases in MPS rates. They can be significant, with up to a 1.7-fold increase using the highest 10 nM dose in the study [129]. So, similar to what we saw earlier with IGF-1 expression, there may be a point where trenbolone stops suppressing MPS and begins increasing it. It is likely this point extends beyond realistic real-world use cases though, as in vivo studies in various animals do not show this same effect. In these cells, rates of protein degradation were also lowered, with the highest dose of TBA causing rate of degradation to be 70% of that shown in cultures with no TBA. This was, at least, a partially AR-mediated effect as flutamide suppresses trenbolone’s ability to stimulate protein synthesis as well as suppress protein degradation rates. Treatment of the cell cultures with JB1 (IGF-1 inhibitor) also impacts trenbolone’s effects on protein synthesis/degradation so it is highly likely these effects require both the AR and IGF-1 receptor to some degree.

Trenbolone has also been shown to suppress amino acid degradation within the liver [37,130]. This can also be a key factor to the overall effects on MPB, as the first step in amino acid degradation takes place there – the removal of nitrogen. In fact, the major site of amino acid degradation in mammals is the liver.

Effects on Bone

Age-related hypogonadism is a major factor contributing to the loss of bone in older men [131]. As we’ve discussed previously, the de facto treatment for hypogonadism is testosterone (TRT). The problem is that TRT only produces modest improvements on bone mineral density in treated subjects [132–133]. Conversely, supraphysiological doses of testosterone fully protects against bone loss, however it comes with a lot of unwanted side-effects [134,135,136]. So, we are back at the place we were at earlier, where we are looking for the protective effects of supraphysiological doses but without the unwanted sides.

Early indications are promising as rodent trials demonstrate trenbolone prevents hypogonadism-induced bone loss in castrated rats to a degree equal to that of supraphysiological testosterone, but without inducing prostate growth or elevations in hemoglobin which are frequently seen with testosterone treatments [3,20].

Trenbolone potentially exerts part of its influence on bone through reductions in circulating corticosterone, via its anti-glucocorticoid activity [14,39]. And, despite trenbolone suppressing estrogen, it still possesses bone-preserving characteristics similar to testosterone. This is similar to what was seen with DHT so it appears as if non-aromatizing androgens are capable of bone protection directly through AR mediated pathways [137–138]. There are still lines of thought out there that believe a small degree of skeletal-specific aromatization of testosterone to E2 is essential for bone protection in males [139]. So, before any conclusions can be drawn, long-term trials with TBA will have to be conducted.

We’ve covered a lot of ground, so I’m going to call this a good stopping point for now. In the next, and final, installment of this series we will cover lipolysis, potential risks, and finish with my concluding remarks and recommendations.

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