Sex-related hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axis adaptation during military training

Reproductive endocrine function adapts to psychological, environmental, and energy-associated stressors. Multistressor environments upregulate hypothalamic-pituitary-adrenal (HPA) axis, causing suppression of the hypothalamic-pituitary-gonadal (HPG) axis, but it is not known if this pattern or its magnitude is sex biased. We compared HPG and HPA axis activity in 9 men and 34 women undergoing Army training. One-hour low-dose gonadorelin and Synacthen tests were conducted at 1 and 29 wk, measuring gonadotrophins and cortisol. Cortisol was measured from hair every 3 mo. Morning and evening salivary cortisol and psychometric questionnaires were measured at six timepoints. Sexes were compared over time by two-way ANOVA. Gonadotrophin responses were significantly higher in women than men in week 1, but no sex difference was seen at week 29 (no significant sex × time interaction). Week 1 cortisol response was higher among men, but week 29 cortisol response was higher among women (sex × time F_(1,44) = 18.0, P < 0.001). Hair cortisol was higher among women than men beforehand, not different between sexes during the first 3 mo, and significantly higher among women during training months 5-11 (F_(3,15) = 3.25, P = 0.024). Morning salivary cortisol was higher among women in weeks 8 and 14, but higher among men in week 29 (F_(4,76) = 4.0, P = 0.005). No differences were seen in evening salivary cortisol. Psychometrics did not change or differ between sexes. HPA axis responses to military training were greater among women than men. HPG axis responses suggest greater downregulation among women. These findings will enable equitable and individualized management of people undergoing periods of intensive physical stress.NEW & NOTEWORTHY We conducted a comprehensive comparison of adrenal and reproductive function in men and women undergoing 11-mo military training. We found progressively elevated cortisol levels and dynamic cortisol response to stress among women, but not men, and suppression of reproductive function among women. The physiological impact of stressful military training was greater among women than men; this could not be explained by energy balance, and sex-specific effects of sleep, socio-ethnographic, or other stressors may be responsible.