Selective Androgen Receptor Modulators (SARMS)
FACTS AND COMPARISONS TO ANABOLICS
The biological actions of androgens are primarily mediated by the androgen receptor. The androgen receptor is expressed in target tissues as the prostate, skeletal muscle, liver, central nervous system, with the highest expression being produced in the prostate and adrenal gland. Men with rare mutations of the androgen receptor have lower lean mass and higher body fat than normal men. The physiological importance of the androgen receptor has been demonstrated as animal studies that administer androgen receptor antagonist (drugs that block the actions of androgens binding to its receptor) during muscle overload have suppressed muscle hypertrophy. This suggests that the androgen pathway has a significant effect in exercise-induced muscle hypertrophy and emphasizes the importance of the increase in the number of androgen receptors in exercised muscle. Additionally, when scientists administered the androgen antagonist flutamide, to rats undergoing puberty resulted in a suppressed muscle growth. Researchers developed SARMS to minimize the side effects of testosterone y promoting full anabolic activity in muscle and bone, while minimizing the undesirable side effects on prostate, hair, skin, and without affecting sperm production and sex drive.
SARMS have full anabolic activity in muscle and bone, yet have minimal effect the on prostate. SARMS are highly specific to the androgen receptor as they have a 1000-fold less binding affinity for any other receptor. SARMS are orally available and so far seem to have minimal effect on the liver. SARMS have a number of beneficial effects in bone, muscle, and sexual function independent from the conversion of androgens into estrogens.
SARMS: Anabolic Activity in Muscle and Bone with Minimal Effect on the Prostate.
Testosterone induced increase in muscle mass is associated with hypertrophy of both type I and type II fibers and increased satellite cell activation. The effect of testosterone is thought to be mediated by the androgen receptor as muscle growth factors in vitro (in test tubes) are blocked by the androgen antagonist bicalutamide (blocks the actions of testosterone from binding to the androgen receptor), indicating that the effects of testosterone are mediated thru the androgen receptor pathway. The androgen receptor signaling pathway enhances the expression of myogenin (Myogenin is an important mediator of muscle growth) and accelerates the expression of muscle growth factors. AR expression is widespread throughout the body and androgens play a desirable role in promoting bone strength, increasing muscle mass, decreasing fat tissue, and increasing muscle strength. A study in the Journal of Steroid Biochemistry and Molecular Biology reported that when resistance trained men had muscle biopsies taken the greatest predictor of males 1-RM strength was not testosterone but the androgen receptor content in the thigh muscle. SARMS are muscle specific compared to testosterone. For example, one study reported that oral doses of SARMS exhibited a >50-fold selectivity for muscle over the prostate. Testosterone propionate had only a 2-fold selectivity for muscle versus prostate. Other studies have reported that the SARM S4 produced greater anabolic activity in muscle than testosterone propionate but had less androgenic activity on the prostate. Additionally, a study published in the journal of Endocrinology reported that SARMS were just as anabolic in muscle compared to testosterone cypionate but less androgenic. In that study, testosterone cypionate increased prostate weight and muscle growth in a dose dependent manner, meaning the more testosterone they used the more muscle hypertrophy was experienced but with similar increases in prostate growth. SARMS showed more anabolic activity in muscle with minimal stimulation of the prostate. Compared with testosterone cypionate, SARMS were more than 200 times more potent in stimulation of muscle and 80 times more selective for muscle versus prostate. Additionally, both testosterone cypionate and SARMS decreased adipose tissue in a dose dependent manner. The study demonstrated that SARMS has the potential to provide a greater safety delivery than testosterone, mainly with low stimulation of the prostate, yet hyperanabolic effects on muscle tissue. SARMS have also been shown to increase skeletal muscle strength.
It should be noted that testosterone increases muscle mass thru multiple pathways: increasing protein synthesis, increasing GH secretion, increasing IGF-1 levels, increasing satellite cell activation, and increasing androgen receptor concentration in muscle. The androgen receptor binding affinity of steroids is only partly responsible for the androgen receptor mediated effects of both physiological and synthetic steroids. For example, it is well known that some steroids are potent anabolic agents, yet bind to the androgen receptor weakly. Another interesting fact is that testosterone can increase lean body mass and reduce fat mass in androgen-deficient men. The skeletal muscle androgen receptor may exert both receptor dependent (testosterone, DHT) and independent actions (intramuscular IGF-1) in the functionally overloaded muscle, which may be related to growth factor signaling. The androgen receptor in muscle is decreased during aging which may be an important contributing factor to the age related decrease in muscle mass that occurs with aging. The development of SARMS for clinical use is promising based on preclinical data owing to their selective high anabolic activity in muscle. SARMS could be useful for the prevention of many muscle wasting diseases and age related decreases in muscle mass without unwanted side effects associated with testosterone. In addition, SARMS may be prevent or treat prostate enlargement as SARMS is a partial agonist on the prostate. SARMS also lack estrogenic activity and do not under go 5a-reduction so it can’t be converted to DHT. The side effects are minimal and the results speak for themselves. d