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

• Slightly higher cortisol concentrations in follicular vs. luteal phase. • Higher cortisol concentrations in menstrual vs. premenstrual phase in precise cycle phase determination. • Majority of studies measuring HPA-axis activity in the menstrual cycle are using single measures of cortisol. • Progesterone derivatives (e.g. ALLO) might decrease cortisol concentrations in luteal/premenstrual phase. 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. [ABSTRACT FROM AUTHOR]