Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications

Abstract

Introduction: Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors depending on each SARM's chemical structure. As a result, SARMs result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in the treatment of breast cancer and cachexia and have also been used as performance-enhancing agents. Here, we evaluate and summarize the current literature on SARMs.

Aim: To present the background, mechanisms, current and potential clinical applications, as well as risks and benefits of SARMs.

Methods: A literature review was performed in MEDLINE using the terms selective androgen receptor modulator, hypogonadism, cachexia, breast cancer, benign prostatic hyperplasia, libido, and lean muscle mass. Both basic research and clinical studies were included.

Main outcome measure: To complete a review of peer-reviewed literature.

Results: Although there are currently no U.S. Food and Drug Agency-approved indications for SARMs, investigators are exploring the potential uses for these compounds. Basic research has focused on the pharmacokinetics and pharmacodynamics of these agents, demonstrating good availability with a paucity of drug interactions. Early clinical studies have demonstrated potential uses for SARMs in the treatment of cancer-related cachexia, benign prostatic hyperplasia (BPH), hypogonadism, and breast cancer, with positive results.

Conclusion: SARMs have numerous possible clinical applications, with promise for the safe use in the treatment of cachexia, BPH, hypogonadism, breast cancer, and prostate cancer. Solomon ZJ, Mirabal JR, Mazur DJ, et al. Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications. Sex Med Rev 2019;7:84-94.

Keywords: Androgens; Drug-Related Side Effects and Adverse Reactions; Hypogonadism; Selective Androgen Receptor Modulators.

Figure 1:. Mechanism of SARM signaling.

Like androgens, SARMs enter the cytoplasm, where they displace the androgen receptor from heat shock proteins. Once bound, they translocate to the nucleus and act as transcription factors by binding androgen response elements (AREs). Depending on the tissue type and regulatory environment of the cell, different co-regulatory proteins help determine and modulate the transcriptional response. HSP = Heat shock protein. AR = Androgen Receptor. ARE = Androgen Response Element.