Selective androgen receptor modulators: a critical appraisal

Area of Science:

• Endocrinology
• Pharmacology
• Molecular Biology

Background:

• Selective androgen receptor modulators (SARMs) were developed to separate anabolic effects from androgenic side effects.
• Historical attempts to achieve tissue selectivity involved modifying the steroid nucleus of androgens.

Purpose of the Study:

• To critically evaluate the evidence for SARMs' tissue selectivity.
• To compare SARMs with traditional androgens regarding efficacy and clinical utility.

Main Methods:

• Review of preclinical and clinical studies on SARMs.
• Analysis of historical androgen research and steroid metabolism.
• Assessment of evidence for differential coregulator recruitment and nongenomic signaling.

Main Results:

• SARMs show favorable preclinical anabolic-androgenic ratios, potentially due to lack of steroidal metabolism.
• Clinical trials indicate some efficacy but lack head-to-head comparisons with conventional androgens.
• Absence of estrogenic activity presents challenges for bone health and sexual function.

Conclusions:

• Clinically meaningful tissue selectivity of SARMs remains uncertain.
• Robust evidence supporting SARMs' superiority over traditional androgens is incomplete.
• Cautious interpretation and further comparative research are warranted for SARMs.