FDA Weighs Long-Term Safety of Off-Label Testosterone Use in Menopausal Women

Specialists at a Food and Drug Administration (FDA) public workshop cautioned on Thursday that critical questions regarding the long-term safety of testosterone therapy remain unanswered, despite its increasing use among menopausal women.

While adult males typically possess total testosterone levels approximately 15 times higher than females, testosterone is the most prevalent sex hormone in premenopausal women, produced at roughly three times the rate of estrogen. As women age, these levels gradually decline, a drop linked to reduced bone density and muscle mass, as well as negative impacts on cognition, mood, sexual function, and energy.

Because the United States currently lacks an FDA-approved testosterone formulation specifically for women, clinicians often prescribe the hormone off-label, utilizing smaller doses of products intended for male patients. Dr. Christina Chang, division director of the division of urology, obstetrics, and gynecology in the FDA’s Center for Drug Evaluation and Research, emphasized that there are no FDA-approved uses for testosterone therapy in menopausal women. She noted the agency is closely monitoring the growing trend of off-label prescribing.

Current evidence supporting testosterone therapy in women is primarily centered on hypoactive sexual desire disorder, a condition defined by persistently low sexual drive that causes distress. However, workshop specialists reported that patients are increasingly seeking the hormone for a broader spectrum of issues, including fatigue and mood changes. According to existing guidelines, testosterone is not considered a treatment for these symptoms.

Diagnosing testosterone deficiency in women is complicated by significantly lower hormone concentrations compared to men. Consequently, there is no established blood-test threshold to confirm a deficiency. Dr. Margaret Wierman, a professor of medicine at the University of Colorado School of Medicine, explained that unlike estrogen, which drops sharply during menopause, testosterone levels decline gradually across the premenopausal stages.

This surge in interest coincides with a broader rise in hormone replacement therapy (HRT). Data from Epic Research indicates that HRT prescriptions for women aged 50 to 65 increased by 72% between 2021 and 2025. This trend follows the FDA’s removal of its strongest safety warnings, known as “black box” labels, from both HRT products and testosterone products earlier this year.

“Menopause is inevitable, women should not have to suffer through it,” Chang stated. She added that to best serve American women, the agency requires high-quality data and is eager to collaborate with manufacturers to obtain it.