Low-dose testosterone administration and oestrogen synthase availability in the female brain: A pilot study

Testosterone and oestrogens play significant roles in female physiology, extending beyond reproductive functions to influence brain health, mood regulation, and behaviour. Testosterone low-dose therapy is increasingly considered for alleviating sexual dysfunction symptoms in postmenopausal women, and has been recently investigated 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 oestrogen synthase (aromatase), which maintains the balance between androgens and oestrogens, remain unexplored. This study investigated the effects of short-term, low-dose testosterone administration on brain oestrogen synthase availability and associated mood and behavioural changes in healthy women. Healthy women were exposed to 1 week of low-dose testosterone (10 mg/day). Binding of oestrogen synthase was examined by [¹¹C]cetrozole positron emission tomography before and during testosterone exposure. Psychometric assessment of depression, anxiety, and aggression was performed at the same time. Peripheral testosterone levels were significantly increased (up to 33-fold) upon treatment, which had no significant effect on brain oestrogen synthase binding in the thalamus, as supported by Bayesian analyses, nor in the hypothalamus and amygdala. Psychometric measures of depression, anxiety, and aggression also remained unchanged by testosterone treatment. These findings suggest that short-term, clinically relevant testosterone administration has no major effects on the brain oestrogen synthase availability in healthy women, which may reassure patients with hypoactive sexual desire disorder considering this treatment. Larger, long-term studies are needed to confirm these results and explore effects in patients with clinical need for testosterone treatment.