HPA axis activity across the menstrual cycle - a systematic review and meta-analysis of longitudinal studies

Differential HPA axis function has been proposed to underlie sex-differences in mental disorders; however, the impact of fluctuating sex hormones across the menstrual cycle on HPA axis activity is still unclear. This meta-analysis investigated basal cortisol concentrations as a marker for HPA axis activity across the menstrual cycle. Through a systematic literature search of five databases, 121 longitudinal studies were included, summarizing data of 2641 healthy, cycling participants between the ages of 18 and 45. The meta-analysis showed higher cortisol concentrations in the follicular vs. luteal phase (d(SMC) = 0.12, p =.004, [0.04 - 0.20]). Comparisons between more precise cycle phases were mostly insignificant, aside from higher concentrations in the menstrual vs. premenstrual phase (d(SMC) = 0.17, [0.02 - 0.33], p =.03). In all included studies, nine samples used established cortisol parameters to indicate HPA axis function, specifically diurnal profiles (k = 4) and the cortisol awakening response (CAR) (k = 5). Therefore, the meta-analysis highlights the need for more rigorous investigation of HPA axis activity and menstrual cycle phase.

Automated summary

This meta-analysis investigates the impact of fluctuating sex hormones across the menstrual cycle on basal cortisol concentrations as a marker for HPA axis activity. The results show higher cortisol concentrations in the follicular phase compared to the luteal phase. In addition, there are higher concentrations in the menstrual phase compared to the premenstrual phase. However, more rigorous investigation of HPA axis activity and menstrual cycle phase is needed.