Lowered Plasma Steady-State Levels of Progesterone Combined With Declining Progesterone Levels During the Luteal Phase Predict Peri-Menstrual Syndrome and Its Major Subdomains.

Chutima Roomruangwong,André F. Carvalho,Frank Comhaire,Michael Maes

doi:10.3389/fpsyg.2019.02446

Abstract

BackgroundIt is unknown whether lowered steady state levels of sex hormones coupled with changes in those hormones during the menstrual cycle are associated with premenstrual syndrome (PMS).ObjectiveTo examine associations between levels of progesterone and oestradiol during the menstrual cycle and PMS considering different diagnostic criteria for PMS.MethodsForty-one women aged 18–45 years with a regular menstrual cycle completed the Daily Record of Severity of Problems (DRSP) for all 28 consecutive days of the menstrual cycle. Blood was sampled at days 7, 14, 21, and 28 to assay oestradiol and progesterone.ResultsWe developed a new diagnosis of peri-menstrual syndrome, which is characterized by increased DRSP severity in pre and post-menstrual periods and increased scores on the major DRSP dimensions, i.e., depression, physio-somatic symptoms, breast tenderness and appetite, and anxiety. This new diagnosis performed better than classical diagnoses of PMS, including that of the American College of Obstetricians and Gynecologists (ACOG). Lowered steady state levels of progesterone, when averaged over the menstrual cycle, together with declining progesterone levels during the luteal phase predict severity of peri-menstrual symptoms. Steady state levels of oestradiol and declining oestradiol levels during the cycle are also related to DRSP severity although most of these effects appeared to be mediated by progesterone.ConclusionA significant increase in menstrual-cycle related symptoms can best be conceptualized as “peri-menstrual syndrome” and may result from insufficient progesterone production (relative corpus luteum insufficiency), which, in part may result from lowered oestradiol production indicating suboptimal pre-ovulatory follicular development.

Highlights

Premenstrual syndrome (PMS) comprises affective, behavioral, and physical symptoms appearing during the luteal phase of the menstrual cycle and ameliorating after the onset of menses (Deuster et al, 1999; Dickerson et al, 2003)
In order to evaluate the validity of the four diagnoses used in the current study, we have used Generalized estimating equation (GEE) analysis with the time series of the total Daily Record of Severity of Problems (DRSP) scores as dependent variables
Discrepancies in some of the above-mentioned case-control studies and the current study may be explained by our findings that the severity of PMS symptoms is predicted by steady state levels of progesterone combined with changes over time in progesterone levels in a distributed lag model

Summary

Introduction

Premenstrual syndrome (PMS) comprises affective, behavioral, and physical symptoms appearing during the luteal phase of the menstrual cycle and ameliorating after the onset of menses (Deuster et al, 1999; Dickerson et al, 2003). A recent meta-analysis shows that the prevalence of PMS is 47.8% (95% CI: 32.6–62.9), with a lower prevalence in France, i.e., 12% (95% CI: 11–13), and a higher prevalence in Iran, namely 98% (95% CI: 97–100) This burdersome condition is commonly observed in adolescent girls and young women with prevalence rates between 58.1 to 92.3% among university students (Acikgoz et al, 2017; Hussein Shehadeh and HamdanMansour, 2018). PMS is an important predictor of perinatal depression (Studd and Nappi, 2012; Buttner et al, 2013; Roomruangwong et al, 2016; Stoner et al, 2017). It is unknown whether lowered steady state levels of sex hormones coupled with changes in those hormones during the menstrual cycle are associated with premenstrual syndrome (PMS)

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Discussion

Conclusion