Best Bodybuilding Drug?

Stack them up (pun intended) and compare to see what is the best anabolic-androgenic steroid (AAS). This is the ongoing competition that is best portrayed by the voluminous tomes on bodybuilding drugs by writers such as William Llewellyn’s Anabolics.

The 800-pound gorilla in the room when it comes to AAS is testosterone. Bodybuilders and athletes opine that there is much to love about testosterone— it dependably builds size, strength, improves mood and frequently enhances sexual arousal and libido. Of course, many responses to testosterone are dose-dependent, including the primary goals of muscular hypertrophy and strength gains. Unfortunately, adverse side effects also become more prevalent and problematic in a dose-dependent fashion during supraphysiologic use. Also, as testosterone is the endogenous (natural) AAS produced by the body, it necessitates the use of supraphysiologic dosing to exceed what the body naturally provides. Unfortunately, this also shuts down endogenous testosterone production— so much of a dose is spent replacing what is shut down by “doping.”

There is also the issue of how the body handles testosterone, using it not only as a hormone, but also as a prohormone. Testosterone readily converts into either estradiol (an estrogen) or DHT (a more potent androgen) in a tissue-specific manner. While this is necessary and beneficial for proper function and health of most tissues in the body, in the setting of supraphysiologic testosterone, both estradiol and DHT also increase. The consequences are side effects that range from cosmetic to catastrophic. As most AAS misuse is limited in dose and duration, AAS users are only familiar with superficial effects: gynecomastia (breast development in males), virilization (male features in women), acne, hair loss and testicular atrophy (small balls).1

A New Class of Drugs

More than 60 years ago, chemists purposefully created analogs of testosterone to reduce the potential for estrogenic and androgenic side effects. This created the class of drugs known as androgenic anabolic steroids. More recently, pharmaceutical companies have pursued non-steroidal alternatives, called selective androgen receptor modulators (SARMs). Note, the difference between AAS and SARMs is not functional, but notational. The correct designations should be s-SARMs for AAS and ns-SARMs for the drugs designed to function at the androgen receptor, but lacking a steroidal “backbone.” This article does not account for ns-SARMs.

Among the many AAS created, mostly during the 1950s and 1960s, several have attracted a strong following among bodybuilders. It is important to appreciate the dissimilarities between bodybuilders and powerlifters, as well as performance athletes. Though bodybuilding is based upon an exercise component (resistance training, as well as fat-reducing aerobic training), the scoring in competition is based upon the relative appearance of the contestants. There is no functional component. Contestants do not perform strength or fitness tests as part of the competition. Thus, the desired effects of any physique-enhancing drugs relates to their ability to improve muscularity, definition and/or symmetry.

As stated earlier, testosterone is highly regarded, and proven as a builder of muscle mass and strength. It is commonly the foundation drug in “stacks” due to this feature— in addition to maintaining physiologic functions that depend upon endogenous testosterone, or its metabolites. However, used as a solo drug (for the sake of a direct comparison), it falls somewhat short due to the propensity to increase water retention and fat accretion at doses used to promote short-term increases in muscle mass. This is particularly pronounced with testosterone-based orals, which advanced bodybuilders do not find suitable for single-drug cycles. Novices will often experience notable changes with the proto-typical eight-week cycle of oral Dianabol, stanozolol or oxandrolone, but the degree of effect is limited.

Oral AAS also carry a greater risk of hepatotoxicity (liver damage) and are associated with potentially harmful changes to the lipid profile (cholesterol) that may increase the risk of cardiovascular events with long-term use, and they do not provide an acceptable risk-to-benefit ratio for many.2,3 It is their convenience and ease of use that appeal to most.

Among the injectable AAS, certain drugs have withstood the test of time. While it is possible that AAS with more “ideal” properties exist in the archives of pharmaceutical companies, accessibility is an issue that needs to be considered. Patrick Arnold, infamous for his role in the BALCO scandal, synthesized norbolethone— an AAS developed but never marketed by Wyeth Laboratories, as well as creating THG.4,5 Both of these “designer steroids” provided performance-enhancing effects, provided to elite cyclists and Olympians. However, too little is known about their effect on body composition or potential risks.6

Most Users Combine AAS

It is incorrect to compare AAS based upon “popularity” as that relates to accessibility, and most users combine AAS with the intention of gaining additive benefits. Deca-Durabolin is a trade name for nandrolone decanoate, a 19-nortestosterone AAS. It is familiar to most, and often included in stacks due to its perceived lesser androgenic potency, mood effect and perceptible gains when added to a testosterone-based stack. However, as a solo agent, nandrolone has not gained a following. In part, this is due to its pharmacokinetics— how long it takes to build up to an effective concentration, and how long it takes to clear from the system.7 Nandrolone can continue to suppress natural testosterone production for months following a standard cycle. Further, though it is protected from aromatization via the aromatase enzyme complex, it is still capable of being converted into estradiol— perhaps at 20 percent efficiency compared to testosterone.

And while nandrolone is thought of as a “less androgenic” AAS, it is in fact more androgenic than testosterone prior to being acted upon by 5-alpha reductase— the enzyme that converts testosterone into DHT. It is true that in tissue containing 5-alpha reductase (e.g., skin, prostate), dihydronandrolone (DHN) is much less androgenic than DHT, even less than testosterone. However, this does not preclude androgenic effects with anabolic dosing.

Lastly, nandrolone also interacts with the progesterone receptor at a relative potency of 10 percent of progesterone (another female sex hormone).8 Though this is thought to aid in relieving joint pain experienced with non-aromatizable AAS, it can exacerbate gynecomastia. Nandrolone is anecdotally associated with AAS-related erectile dysfunction when used as a solo agent, though this is not well documented in the medical literature.

Trenbolone: Near-Mythical Status

There is one AAS that raises the interest of most experienced bodybuilders. Trenbolone has a near-mythical status due to its discontinuation in 1997. Then, a source for trenbolone was revealed by none other than the late Dan Duchaine, who disclosed a method for extracting trenbolone acetate from pellets designed to enhance meat production after being implanted into cattle. This form of trenbolone was the acetate ester, a shorter-acting but more rapidly bioavailable form that provided exactly the kind of results that the old-school bodybuilders whispered about during the 1970s through the 1990s. Despite the absence of a licensed and approved human pharmaceutical source, several different esters are now widely available through black-market sources, produced with varying quality and purity in “underground laboratories.” These esters include the previously mentioned acetate, an enanthate ester, as well as the same ester used in the original Parabolan formula, cyclohexylmethylcarbonate.

Trenbolone’s reputation is for building muscle size, strength and furnishing a rock-hard physique with a dry appearance. It is most commonly used along with testosterone, as the two used together have reliably provided greater gains than an equivalent testosterone ester single-agent cycle. Also, the gains are believed to be better retained, perhaps in part due to an greater recruitment of satellite cells.9 Satellite cells donate another nucleus to muscle fibers, raising the potential volume of a growing muscle. This may also aid in “muscle memory,” though this effect has not been noted in anecdotal reports. Of course, it would be impossible for an individual to assess.

Commonly, testosterone is the dominant AAS, with trenbolone added in complementary but lesser doses. However, there are some in underground communities who claim that trenbolone should be used as the dominant AAS in the greater dose, with testosterone being held to replacement doses only.10 The rationale behind those advocating this position is intriguing, as they state that testosterone serves only to compete with trenbolone in most effects, and that the need for higher doses of testosterone is to counter the potential trenbolone-induced hyperprolactinemia. Instead of relying upon testosterone to compensate for the libido-crushing, erectile dysfunctional effects of prolactin (a posterior pituitary hormone), these proponents suggest adding an adjunct drug to combat prolactin production— much like aromatase inhibitors are used in testosterone-based cycles.11

Moderate Dosing

Nonetheless, the common dosing for trenbolone is surprisingly moderate, as reported by six-time Mr. Olympia Dorian Yates in an interview with Muscular Development. Trenbolone is commonly dosed for bodybuilding purposes (acknowledging that it is typically stacked with other AAS), in a dosing range of approximately 75 to 150 milligrams every two or three days when used in the acetate ester form. The total administered is similar for the other esters, accounting for the different pharmacokinetics. This makes a recent paper published in the scientific journal Steroids particularly relevant.12 The group of Australian researchers provided trenbolone in a dose that is equivalent to the reported dosing schemes used by bodybuilders. The male rats were dosed using pellets at two milligrams per kilogram per day. This would be the equivalent of a 200-pound adult human male receiving between 126 to 210 milligrams per week— or the previously stated 76 milligrams, every-other-day schedule of trenbolone acetate.13 It is interesting that both cattle and the rats respond to implanted pellets, yet this method has not found its way into the bodybuilding practices.

In the Australian study, the researchers were investigating the effect of trenbolone on body composition, markers of cardiovascular risk factors, insulin sensitivity as well as the rats’ ability to survive a created “heart attack.” In addition to dissecting the heart, the liver and testes of the rats were removed and examined under a microscope for possible damage. Contrary to what popular media and politicized science would suggest, the findings were remarkably favorable, with no adverse effects noted. It is also relevant to note that the rats were intact, meaning they had not been circumcised (much to the rats’ relief, I am sure), increasing the relevance to human application.

To provide an accurate assessment of the study findings, it is best to quote the authors’ conclusion: “In conclusion, 2 mg/kg/day TREN treatment of eugonadal rats improved body composition, lipid profile and insulin sensitivity without: (1) adverse cardiovascular effects or increasing myocardial susceptibility to I/R injury; and (2) compromised hepatic structure or function… Further investigation into the comparative benefits conferred by trenbolone therapy relative to the current gold standard, testosterone, are well justified by these findings…”12

Changes in Body Composition

The most relevant effects for bodybuilders are the body composition changes seen with trenbolone treatment. The control rats that did NOT receive trenbolone gained eight percent body mass over the course of the study, with all of that gain (and then some) accounted for by an increase in fat mass. Body composition was measured by DEXA, so the results are reliable. The trenbolone-treated rats did not gain any significant mass during treatment. HOWEVER, there was a significant increase in lean mass, with a concordant reduction in fat mass. The trenbolone-treated rats saw a gain of 11 percent in lean mass, and dropped 37 percent of fat mass. Compare that to the unchanged lean mass of the control rats and 34 percent increase in fat mass. The results would be outrageous in a human study.

This change in body composition was not overtly stressful to the organs or metabolism of the rats. In fact, the opposite occurred— as it was discovered that the body became more sensitive to the signaling function of insulin. Insulin resistance precedes type 2 diabetes and is believed to play a role in a number of chronic diseases. The trenbolone-treated rats demonstrated a HOMA-IR score (measure of insulin resistance) that was roughly half that of the control rats.

Additionally, and particularly relevant in light of the presumptive (and possibly incorrect) black box warning now being attached to pharmaceutical testosterone products, markers of cardiovascular risk IMPROVED for the trenbolone-treated rats. Those opposed to androgen replacement therapy would point out that HDL (good) cholesterol dropped by 57 percent. In fact, all cholesterol values dropped with the HDL:LDL ratio IMPROVING significantly, as well as a 51 percent drop in triglycerides. Further, when a heart attack was induced surgically, trenbolone-treated rats responded the same as the control rats, with no increase in tissue damage markers. The researchers suggest that the reduction in DHT, secondary to the suppression of endogenous testosterone, may have protected the heart from some of the ischemia reinjury (heart attack related) damage.

Yes, endogenous testosterone fell considerably, as would be expected due to the negative feedback to the hypothalamic-pituitary-testes regulatory system. Further, the prostate was enlarged approximately 50 percent, but no evidence of malignancy was reported. In other words, it was “normal” prostate growth and not cancer.

Best Bodybuilding Drug?

This rat study mimics the anecdotal reports given by bodybuilders on the effects of trenbolone, at a dose range commonly practiced in that community. Improvement in body composition, with positive health markers and no overt evidence of organ damage in the studied tissues, is promising. Now, many bodybuilders have reported that trenbolone is difficult to tolerate, with accelerated hair loss, sleep disruption, erectile dysfunction, mood changes and “tren cough.” Clearly, there is need for more formal study. However, the current findings further support investigating the use of trenbolone further, in contrast to previous papers suggesting a contribution to neurodegenerative conditions, such as Alzheimer’s.14,15 If the findings in this recent rat study are indicative of trenbolone’s effects in humans, it certainly supports the argument that trenbolone could vie for the title of “best bodybuilding drug.”