Transdermal Testosterone Gel for Female Sexual Interest and Arousal Disorder in Peri- and Post Menopause

Overview

Hypoactive sexual desire disorder (HSDD) will be described as the most common form of female sexual dysfunction, particularly affecting peri- and postmenopausal women and associated with significant distress and reduced quality of life; although DSM-5 reclassified it under Female Sexual Interest/Arousal Disorder, HSDD criteria will continue to be used in clinical trials. The TESTA-MIND study will evaluate the efficacy and safety of a standardized compounded transdermal testosterone gel in a randomized, double-blind, placebo-controlled design to address the lack of FDA-approved options and limited high-quality evidence for treating decreased libido in women.

Hypoactive sexual desire disorder (HSDD) is the most prevalent form of female sexual dysfunction, particularly affecting peri- and postmenopausal women. Epidemiological studies estimate that between 8-14% of postmenopausal women experience clinically significant reductions in sexual desire that cause distress or interpersonal difficulty, significantly impacting quality of life and intimate relationships. In 2013, with the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the diagnosis of HSDD was merged with female sexual arousal disorder under the category of Female Sexual Interest/Arousal Disorder (FSIAD). Despite this reclassification, clinical and pharmacological trials continue to use HSDD criteria, given their clearer operationalization and applicability in interventional studies. Testosterone has long been recognized as a key modulator of female sexual desire and arousal. Observational studies show that circulating androgen levels decrease substantially with age and after menopause. Clinical trials of transdermal testosterone have demonstrated improvements in sexual function, specifically increased frequency of satisfying sexual events, enhanced desire, and reduced distress compared with placebo (7-9). Nevertheless, most clinical studies have utilized pharmaceutical-grade formulations not currently available in the United States, leading many clinicians to rely on compounded testosterone creams. Currently, no FDA-approved testosterone therapy exists for women, and off-label use varies widely in formulation and administration. Transdermal preparations may provide a physiologic, steady release, and offer practical advantages over patches or systemic therapy, but robust randomized data remain scarce. Evidence regarding compounded testosterone is limited and highlights concerns about variability in formulation, dosing accuracy, and absorption. Professional societies caution against the routine use of compounded hormones, citing the lack of FDA oversight, inconsistent bioavailability, and absence of long-term safety data. While compounded testosterone may represent a pragmatic solution in the absence of FDA-approved formulations, its use requires rigorous evaluation under standardized trial conditions to establish both efficacy and safety. The TESTA-MIND study is designed to address this evidence gap by investigating the efficacy and safety of a standardized compounded testosterone gel in peri- and postmenopausal women with decreased libido. By conducting a randomized, double-blind, placebo-controlled trial, we aim to provide high-quality data on the therapeutic role of testosterone in this underserved population, while addressing the clinical uncertainty and professional society concerns that currently limit its widespread adoption.