Selective Androgen Receptor Modulators in Women: What Do We Know, and What Is Still Missing

Area of Science:

• Endocrinology and Reproductive Science
• Pharmacology
• Oncology

Background:

• Androgen receptor (AR) signaling impacts female physiology, but is understudied compared to males.
• Selective androgen receptor modulators (SARMs) aim for tissue-selective anabolic effects with fewer side effects.
• The effects and safety of SARMs in women are not well-established.

Purpose of the Study:

• To review preclinical and clinical evidence on SARM use in female rodents and women.
• To focus on AR biology, tissue selectivity, therapeutic potential, and safety of SARMs in females.
• To identify knowledge gaps and the need for further sex-specific research.

Main Methods:

• Narrative review of literature from PubMed, Scopus, and Google Scholar.
• Inclusion of experimental and clinical studies on sex-specific AR signaling and SARM effects.
• Synthesis of data on SARM outcomes in female models and human subjects.

Main Results:

• Preclinical studies show SARMs can improve muscle, bone, and sexual motivation in female models.
• Clinical studies in postmenopausal women indicate increased lean body mass with limited androgenic effects.
• Reported side effects include inconsistent functional benefits, lipid alterations, and elevated liver enzymes.
• AR-targeted SARMs demonstrate potential antitumor activity in specific breast cancer types.

Conclusions:

• SARMs exhibit therapeutic potential for various conditions in women, including muscle wasting and certain cancers.
• Long-term safety and efficacy of SARMs in women require further comprehensive investigation.
• Sex-specific clinical trials are essential to fully characterize SARM benefits and risks in the female population.