Low-dose testosterone administration and estrogen synthase availability in the female brain

Testosterone and estrogens play significant roles in female physiology, extending beyond reproductive functions to influence brain health, mood regulation, and behavior. Testosterone low-dosage therapy is increasingly considered for alleviating sexual dysfunction symptoms in women, and has been recently proposed as therapy for depressive symptoms, though the mechanisms and safety of this approach are not entirely clear. Specifically, the effects of testosterone use on brain estrogen synthase (aromatase), which maintains the balance between androgens and estrogens, remain unexplored. This study investigated the effects of short-term, low-dose testosterone administration on brain estrogen synthase availability and associated mood and behavioral changes in healthy premenopausal women. Healthy women (aged 22–33) were exposed to one week of low-dose testosterone (10 mg/day). Availability of estrogen synthase was examined by [ ¹¹ C]cetrozole positron emission tomography before and after testosterone exposure. Psychometric assessments of depression, anxiety, and aggression were administered at the same times. Peripheral testosterone levels were significantly increased (up to 33-fold) by the treatment, which had no significant effect on brain estrogen synthase availability. Psychometric measures of depression, anxiety, and aggression also remained unchanged post-treatment. These findings suggest that short-term, clinically relevant testosterone administration does not impact the brain androgen-estrogen conversion in healthy premenopausal women, which may reassure patients with hypoactive sexual desire disorder considering this treatment modality. Larger, long-term studies are needed to confirm these results and explore effects in patients with diverse symptoms and treated with testosterone.