Abstract:

HPA axis (Hypothalamic - Pituitary - Adrenal, HPA) dysfunction determines the formation or deterioration of stress-related emotional disorders. As a special stress-related disease, premenstrual syndrome (PMS) appears before menstruation and disappears after menstruation. This stable and explosive phenomenon reflects acute stress. On the other hand, the premenstrual discomfort symptoms are considered chronic stress, which may last about 30 years. In order to provide a more comprehensive understanding of the pathological mechanisms of PMS, we relied on two types of the activity patterns of HPA axis, namely activity patterns at the baseline level and activity patterns after experimental manipulations on stress levels. The current meta-analysis study included 32 studies (total sample size N = 1280) from 1990 to 2021. We investigated the difference of cortisol levels in luteal phase and follicular phase between PMS women and controls. In addition, we investigated the moderating roles of the cortisol measurement method, cortisol measurement time, PMS/PMDD sample size, and diagnostic type. Because of age-related changes in female hormone secretion and regional differences in menstruation attitude, we further investigated the moderating roles of age and area.
We found that the cortisol of PMS individuals in the luteal phase was significantly lower than that of the controls at the baseline level. This effect was moderated by the time of cortisol measurement. At follicular stage, there was no significant difference in cortisol content between PMS women and controls. Similarly, in the experimental studies manipulating stress levels, the cortisol content of PMS women in the luteal phase was significantly lower than that of the controls, but the two groups did not differ in the cortisol content of the follicular phase. The moderating roles of cortisol measurement method, PMS/PMDD sample size, diagnostic type, age and area were not significant.
The findings suggested that the persistent changes of the HPA axis and blunted reactivity of HPA axis to pressure might be pathological mechanisms of PMS. The inactivation of the HPA axis at the baseline reflected the lasting change of the neurobiological system due to long-term ineffective activation, while the inactivation of the HPA axis in the experimental studies directly showed blunted reaction to subsequent stressors. Blunted baseline cortisol response may be a risk factor to the development of PMS. Thus, future studies need to further clarify the role of blunted baseline cortisol response on the occurrence of PMS using a longitudinal design.
In addition, the results of the follicular phase were unstable in both the baseline and experimental studies, influenced by depression history and trauma experience.
The study responds to the controversy of the existing research findings on the topic and provides a deeper understanding for the pathological mechanisms of PMS. Based on the findings of this study, the roles of the time effect of cortisol measurement and stress regulation strategies should be considered in future research.

Key words: premenstrual syndrome, cortisol, hypothalamic-pituitary-adrenal, HPA, meta-analysis