SARM or Selective androgen receptor modulators are a novel group of androgen receptor ligands. They are expected to have the same effects as androgenic drugs but be much more careful in their action, enabling them to be used for more uses than anabolic steroids. SARMs imply a new era of tissue-selective androgens with an unexplored potential to treat several diseases.
Structure of Testosterone
Currently applied androgens for male hormone replacement therapy are injectable or skin delivery formulations of testosterone or testosterone esters. Injectable testosterone esters like testosterone enanthate, propionate, or cypionate, produce undesirable fluctuations in testosterone blood levels, with high levels shortly after injection and excessively low afterwards. Skin patches provide a better blood level profile of testosterone, but skin irritation and daily application still limit their usefulness.
None of the SARMs yet developed are genuinely selective for anabolic effects in muscle or bone tissues without producing any androgenic effects in tissues such as the prostate gland.
Selectivity In Men
If the target is bone growth in older men with osteopenia or osteoporosis, SARMs ostarine targeting bone and muscle tissue but with decreased activity on the prostate or testes would be more desirable.
Selectivity In Women
A SARM for women would ideally stimulate bone retention, libido, and other function that androgens can influence, without negative side-effects such as the development of male gender characteristics (virilization) and increased LDL/HDL ratios, liver dysfunction, and so forth.
Use of SARMs
Sports
2015 Will Grier Allegedly tested positive for Ligandrol
2017 Joakim Noah Banned for twenty games by the NBA for testing positive for Ligandrol
2019 Sean O’Malley Temporarily suspended after his sample tested positive for Enobosarm
2019 Beatriz Haddad Maia Provisionally suspended after testing positive for SARM
2019 Shayna Jack Forced to withdraw after testing positive for Ligandrol
Male Contraception
SARMs show promise for use as a method of male contraception in animals. Exogenous testosterone interferes with spermatogenesis via negative feedback on the hypothalamic-pituitary-gonadal axis. A SARM markedly suppresses spermatogenesis for reducing peripheral testosterone levels to decrease testicular and epididymal size.
Osteoporosis
Many SARMs have trophic effects on bone. SARM displays binding to both AR and estrogen receptors (ER) without androgenic effects and can completely restore bone loss in orchidectomized mice. It proves to be especially effective as adjuncts in treating osteoporosis or other conditions that lead to suboptimal bone density and mineralization.
Prostate Cancer
Prostate cancer may also be ripe for address by SARM. It can reach high tissue concentrations in the prostate and act as an AR antagonist in prostate cancer (PCa) cell models with efficacy. SARMs helps in prostate cancer management for tissue targeted imaging.
Sexual Medicine
Several studies have evaluated the effects of local vaginal testosterone application, with influences ranging from lower vaginal pH, increased lactobacilli, and improved vaginal maturation index. Several clinical trials using transdermal testosterone for female sexual dysfunction in women with low serum testosterone showed improvements in sexual desire, pleasure and orgasms.
There is little controversy surrounding the critical role of testosterone in male libido and sexual function in men. Many trials and studies have established the sexual benefits of exogenous testosterone use for men. The best SARMs could be as effective as treatment with testosterone and its derivatives in promoting male libido.
Benign Prostatic Hyperplasia
Modulation of the AR using SARMs could also have a role in treating benign prostatic hyperplasia (BPH), primarily via immunomodulatory mechanisms. Activation of the AR by dihydrotestosterone leads to a reduced inflammatory response in cultured human prostatic stromal cells.
Alzheimer’s Disease
Hypogonadal men demonstrate a decrease in various cognitive processes, including episodic memory, working memory, processing speed, visual-spatial processing and executive function. Higher free testosterone index was associated with better visual and verbal memory scores, visuospatial functioning, visual-motor scanning, and a decreased rate of longitudinal decline in visual memory. SARM increases the activity of neprilysin and systemic anabolic effects with reduced androgenic effects.
Muscular Dystrophy
Another group of diseases that may benefit from interventions with SARMs is muscular dystrophies. SARMs administered to patients with DMD would theoretically increase muscle mass, and protein synthesis levels comparable to that observed with oxandrolone without the off-target side effects.
Cachexia
The most promising potential applications of SARMs are cachexia. It is a consequence of the therapy of HIV, cancer, immobilization, and chronic glucocorticoid use. In healthy individuals, muscle exists in a state of equilibrium between breakdown and synthesis, and any alteration to the rate of degradation or protein synthesis can favour atrophy or hypertrophy.
Breast Cancer
There is currently a clinical trial in the recruitment phase seeking to evaluate pembrolizumab and enobosarm co-therapy to treat AR-positive metastatic triple-negative breast cancer.
Safer Than Testoserone
Testosterone therapy (TTh) is currently the mainstay treatment for hypogonadism and is an option for treating cancer-related cachexia. TTh can lead to gynecomastia due to estrogen aromatization, erythrocytosis, reduced spermatogenesis, acne, male pattern baldness, and undesirable alterations in serum lipids. SARMs seem to be much better endured with few incidences of severe adverse effects.
Potential For Abuse
The anabolic effects of SARMs and their lack of androgenic side effects have made them of great interest to the bodybuilding community and create abuse among competitive athletes.
Conclusion
SARMs have diverse possible clinical applications, with hope for safe use to treat cachexia, hypogonadism, BPH, breast cancer, and prostate cancer. While steroid hormones have practical clinical applications, their widespread activation of AR receptors gives rise to treatment-limiting side effects. Like the SERMs before them, SARMs and their tissue selectivity demonstrate the potential to revolutionize the treatment of many debilitating diseases.