SARM-ing Up Your Gains - Steroid-Like Lean Mass Gains W/Out(?) Shut-Down and Other "Roid-Like" Side Effects

SARMs may build muscle, but they don't have significant effect on body fat and thus the visibility of the muscles.

Scientists from the Institute of Cardiovascular Research and Sports Medicine at the internationally well-known German "anti-doping university", i.e. the German Sport University Cologne, have recently published an interesting paper in which they compared (to my knowledge for the first time) how metandienone aka dianabol, estradienedione and the selective androgen receptor modulator (SARM) S-1 affect the body composition, hormone levels and selected health parameters of ... yeah, of course, of rodents.

Before you are now telling me once more that "rodents are no little men", let me remind you of the fact that other SARMs, like LGD-4033 have recently been tested in humans at the Boston Medical Center (Basaria. 2013).

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In said study, Basaria et al. found that 28 days. on this experimental drug lead to highly significant dose-dependent increases of the lean mass of their young, healthy male subjects who didn't even train, Against that backround it is highly unwarranted to grumble that mice are no little men and this study says nothing about possible effects in human.

I do agree: Future human studies appear warranted, but a direct comparison to "toxic" steroids, such as the one that was done in the study at hand, will probably not get the approval of the ethics commission of any Western University, anyway. To circumvent this problem and still learn something about the effects of anabolic steroids in humans, the Germans recruited a handful of "bros" who were juicing anyway and used their (lowered) hormone levels, as well as those of non-juicing bodybuilders as a reference (yes, they drug-tested them to be sure).

Currently available SARMS (Iasuja. 2012)

A word of caution: While most of the studies indicate little to no effect on prostate weight and luteinizing hormone (LH), there is experimental and anecdotal evidence that very high dosages of SARMs can - despite acting as partial antagonists of the androgen receptor in the prostate and brain - have less pronounced, but still negative effects on your hormonal endocrine system. Against that background and in view of the fact that some SARMs are in fact used to block the growth of prostate cancer, "shut down" should be more of a concern than benign or carcinogenic growth of the prostate. So, get regular blood work (LH)!

Now that the "rodent-thing" is out of the way, let's take a look at what the scientists from the  Department of Cellular and Molecular Sports Medicine actually did. As previously mentioned, the study was conducted to analyze combined effects of anabolic steroids and training on the hypothalamic–pituitary–gonadal axis.

"Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17b-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined" (Hengevoss. 2015). 

As previously hinted at, Hengevoss et al. got data to compare the effects to from (a) six human volunteers who were single treated with 1-androstenedione and (b) abusing and clean body builders whose serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined, as well.

Figure 1: Overview of the (imho) most significant results (Hengevoss. 2015).

The results of the study shows that, in rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Unlike the anabolic properties, the LH-suppressive properties were yet present only with metandienone and estradienedione but not with S-1 that was administered at a human equivalent dose of 7.5-75mg/day.

What other SARMs are there? The most prominent research chemicals that bind to the androgen receptor and act as selective agonists in tissues like muscle and bone, but antagonists in the prostate and hypothalamus (➲ this is how they build muscle and bone, without affecting prostate health or triggering shut down) are unquestionably S4 and ostarine. Both are already heavily (ab-)used in the bodybuilding scene. The previously mentioned LGD-4033 (see Figure 2) is the powerful and highly selective new kid on the block and with agents like S-40503, a recently developed tetrahydro-quinoline and other new SARMs, several new research chemicals are already on the horizon... obviously they are all just used by scientists to treat sarcopenia, not available on the (grey) market and not being abused by athletes all around the world ;-)

As it was to be expected, the administration of estradienedione resulted in an additional increase of E2. What is a bit surprising, though is the S-1-induced increase in cortisol, which is in contrast to the the effects the single administration of 1-androstenedione had on the six previously "non-using" young men who saw decreases in both cortisol and inhibin B serum concentrations. LH was not affected.

Table 1: Overview of the results of the comparison of drug-using (ABB) vs. clean bodybuilders (BB). As you can see, both E2 as well as the thyroid hormones were affected also in those who only trained hard (Hengevoss. 2015).

In abusing body builders who used a range of steroids (testosterone, nortestosterone, metandienone and various prohormones) a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected (see Table 1 for a comparison of drug vs. training induced endocrine changes).

Figure 2: LGD-4033 has recently been shown to dose-dependently build up to 1.2-1.3kg of lean mass in young men, even if they don't train (Basaria. 2013).

Overall, the study at hand does thus suggest that (a) SARMs, when they are used in high(er) dosages have similar anabolic properties as two of the "muscle building classics" - most prominently dianabol. The results of the study also confirm that these effects come at minimal side effects of which the comparison of using and non-using bodybuilders (Table 1) shows that not all of the endocrine changes that are commonly observed in bodybuilders are a result of steroid abuse. The increases in estrogen (E2) and T4, as well as the decrease in TSH, the scientists observed, appear to be steroid-unrelated "normal" reactions to intense workouts | Comment on Facebook! 

References:

• Basaria, Shehzad, et al. "The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men." The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 68.1 (2013): 87-95.
• Hengevoss, Jonas, et al. "Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis." The Journal of Steroid Biochemistry and Molecular Biology (2015).
• Iasuja, Ravi, Mikhail N. Zacharov, and Shalender Bhasin. "The state-0f-the-art in the development of selective androgen receptor modulators." Testosterone: Action, Deficiency, Substitution (2012): 459.