Selective Androgen Receptor Modulators: A Critical Appraisal

Selective androgen receptor modulators (SARMs) were developed to separate anabolic effects from androgenic effects through tissue selectivity. While preclinical studies show favorable anabolic-androgenic ratios, this may be due to the lack of steroidal metabolism rather than true selectivity. Emerging evidence points to differential recruitment of coregulators and nongenomic signaling pathways as potential contributors to tissue selectivity, but clinical significance is unclear. Clinical trials show some efficacy in body composition and anti-tumor activity, but these results may not surpass those of conventional androgens due to a lack of direct comparisons. The absence of estrogenic activity in SARMs presents challenges for bone health and sexual function in men. Overall, SARMs are promising but require more robust evidence to confirm their superiority over traditional androgens.