Sex hormones exert a significant influence on the onset, clinical course, and prognosis of severe mental illnesses in women. Across the reproductive lifespan, fluctuations in oestrogen, progesterone, and other sex steroids shape both vulnerability to and expression of psychiatric symptoms. The oestrogen protection hypothesis, particularly well-supported in psychotic disorders such as schizophrenia, posits a neuroprotective role of oestrogens during the reproductive years. Evidence from preclinical, clinical, and epidemiological studies suggests that women typically experience a later onset of illness, better social and functional outcomes, and greater treatment responsiveness prior to menopause. However, the menopausal transition often heralds a worsening of symptoms and an increased need for pharmacological intervention.

Sex hormones not only modulate psychopathology but also interact with drug metabolism through effects on Cytochrome P450 enzymes, influencing antipsychotic efficacy and tolerability. Moreover, selective oestrogen receptor modulators (SERMs), such as raloxifene, have demonstrated therapeutic potential in alleviating psychiatric symptoms, particularly in postmenopausal women. The interaction between sex and stress hormones further contributes to individual variability in symptom severity, treatment response, and comorbid somatic conditions.

This special issue aims to explore the complex interplay between sex hormones and severe mental illnesses in women, addressing key questions regarding menstrual cycle–related symptom fluctuations, reproductive stage–specific vulnerability, and the impact of hormonal transitions on treatment outcomes and long-term prognosis.