Estrogen - A key neurosteroid in the understanding and treatment of mental illness in women

The commentary is an invited brief about my contribution to Psychiatry Research. My work has built on the "estrogen hypothesis", as stated by Hafner, Riecher-Rossler and Seeman in the 1990's. This hypothesis was that estrogen provides 'protection' against the early onset of severe schizophrenia in women, and with decreasing brain estrogens at the menopause, mental ill health worsens in women. In this paper, results from clinical trials conducted over many decades, that involved administering exogenous estrogen in different types and doses, show an overall positive impact - with improved symptoms of schizophrenia in women. This led to the conduct of further successful clinical trials of gonadal hormone treatment in women with PMDD and menopausal depression, plus understanding more about depression caused by hormone contraceptives. The role of estrogens in stress vulnerability is reflected in the sex-dependent reaction to childhood trauma, which has led to our new work in the neurobiological effects of early life trauma in women.