Biological sex and menstrual cycle phase modulation of cortisol levels and psychiatric symptoms in a non-clinical sample of young adults

Prior research examined the complex, bidirectional interplay of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal axes and their roles in (clinical) cognitive/behavioral functions. Less well understood are contemporaneous relationships in non-clinical samples. This pilot study explored cortisol in relation to psychiatric symptoms/personality as a function of self-reported menstrual cycle phase and sex differences in a non-clinical, young adult sample. Consistent with literature and hypotheses, cortisol levels were lowest during early-follicular, intermediary during late-follicular, and highest during mid-luteal phases (not significant), and greater among males than early-follicular females. An acute stressor uniformly affected cortisol across phases and sex, though magnitude and time course differed. Psychiatric symptoms were greater among early-follicular/late-follicular females versus males, and early-follicular and/or late-follicular versus mid-luteal. Contrary to hypotheses, positive psychotic-like symptoms were greater among males than (mid-luteal) females. Cortisol inversely related to early-follicular symptoms, and directly related to late-follicular/mid-luteal symptoms. Results suggest menstrual cycle phase modulates non-clinical psychiatric symptomatology and HPA activity. Findings tentatively bolster a dimensional/continuum model of psychopathology with implications for understanding neurobiological underpinnings and risk/protective factors for mental/physical health conditions, particularly those marked by sex differences and neuroendocrine dysfunction (depression/schizophrenia/Alzheimer's/multiple sclerosis). We speculate a dose-response cortisol effect on symptoms, modulated by endogenous gonadal hormones via gene expression.