Menopause and mental well-being: timing of symptoms and timing of hormone treatment

In the aftermath of the Women's Health Initiative studies, both the clinical and basic science communities had to sort out divergent results among experimental findings, observational data and randomized controlled trials in order to establish a shared analysis. The scientific community formally debates the role of different HRT formulations, hormone doses, time of treatment initiation since the menopause and the age of treated women. Basic scientists demonstrated that the multiple neuroprotective effects of estrogen on brain cells may induce a differential biological response according to the time of treatment. Progesterone (but not all synthetic progestins) also has pivotal neuroactive functions in animal models of reproductive aging. Additionally, epidemiological surveys provide information regarding the detrimental role of hypogonadism on mental well-being. The present article briefly summarizes current evidence supporting the neuroactive role of estrogen, with reference to the clinical finding sustaining the intriguing hypothesis of the early female brain senescence as a highly responsive period to estrogen treatment.