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

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.

The menstrual cycle may not be limited to the endometrium but also may impact gut permeability

“…Furthermore, we verified that the diagnosis of PMS according to Biggs and Demuth (2011) as well as the diagnoses of PeriMS and MCAS, but not the ACOGbased PMS diagnosis, were externally validated by levels of the sex hormones oestradiol and progesterone (Roomruangwong et al, 2019). In addition, a diagnosis of PMS according to Biggs and Demuth (2011) was only predicted by lower steady-state levels of progesterone in the luteal phase (Biggs & Demuth, 2011), while the PeriMS and MCAS diagnoses were significantly related to both sex hormones (Roomruangwong et al, 2019). Lower steady-state levels of progesterone averaged over the luteal phase coupled with decreasing progesterone levels during the luteal phase also predicted changes in severity of the DRSP as well as alterations in severity of its four subdomains, namely a) depressive symptoms; b) fatigue and physio-somatic symptoms; c) increased appetite and craving combined with breast tenderness and swelling; and d) anxiety (Roomruangwong et al, 2019).…”

“…The presence of PMS was considered when the total DRSP score was ≥70 on day −5 to −1 of menses and when there was a 30% difference between premenstrual (day −5 to −1) and postmenstrual (day 6-10) scores (Endicott et al, 2006;Biggs & Demuth, 2011;Qiao et al, 2012). In addition, participants were also categorised in those who had PeriMS with increased DRSP ratings during the perimenstrual period (day 1+ day 2 þ day 24-28) and MCAS (Roomruangwong et al, 2019). We also computed scores of the four subdomains of the DRSP, namely a) depressive dimension; b) physio-somatic component; c) increased appetite and craving combined with breast tenderness and swelling; and d) anxiety dimension (Roomruangwong et al, 2019).…”

“…Another gold standard method used to diagnose PMS includes measurement of the Daily Record of Severity of Problems (DRSP): women with a total DRSP score ≥70 on day −5 to −1 of menses and having at least a 30% difference between pre-and postmenstrual scores are diagnosed with PMS (Endicott et al, 2006;Biggs & Demuth, 2011;Qiao et al, 2012). In a recent study, two new case definitions were identified, namely 1) peri-menstrual syndrome (PeriMS), which refers to women with increasing DRSP ratings during the perimenstrual period (day 1 þ day 2 þ day 24-28); and 2) menstrual cycle-associated symptoms (MCAS), which delineates women with increased DRSP ratings all over the menstrual cycle (Roomruangwong et al, 2019). Furthermore, we verified that the diagnosis of PMS according to Biggs and Demuth (2011) as well as the diagnoses of PeriMS and MCAS, but not the ACOGbased PMS diagnosis, were externally validated by levels of the sex hormones oestradiol and progesterone (Roomruangwong et al, 2019).…”

“…In a recent study, two new case definitions were identified, namely 1) peri-menstrual syndrome (PeriMS), which refers to women with increasing DRSP ratings during the perimenstrual period (day 1 þ day 2 þ day 24-28); and 2) menstrual cycle-associated symptoms (MCAS), which delineates women with increased DRSP ratings all over the menstrual cycle (Roomruangwong et al, 2019). Furthermore, we verified that the diagnosis of PMS according to Biggs and Demuth (2011) as well as the diagnoses of PeriMS and MCAS, but not the ACOGbased PMS diagnosis, were externally validated by levels of the sex hormones oestradiol and progesterone (Roomruangwong et al, 2019). In addition, a diagnosis of PMS according to Biggs and Demuth (2011) was only predicted by lower steady-state levels of progesterone in the luteal phase (Biggs & Demuth, 2011), while the PeriMS and MCAS diagnoses were significantly related to both sex hormones (Roomruangwong et al, 2019).…”

“…In addition, a diagnosis of PMS according to Biggs and Demuth (2011) was only predicted by lower steady-state levels of progesterone in the luteal phase (Biggs & Demuth, 2011), while the PeriMS and MCAS diagnoses were significantly related to both sex hormones (Roomruangwong et al, 2019). Lower steady-state levels of progesterone averaged over the luteal phase coupled with decreasing progesterone levels during the luteal phase also predicted changes in severity of the DRSP as well as alterations in severity of its four subdomains, namely a) depressive symptoms; b) fatigue and physio-somatic symptoms; c) increased appetite and craving combined with breast tenderness and swelling; and d) anxiety (Roomruangwong et al, 2019). Therefore, we concluded that the diagnosis of PeriMS comprises the most accurate diagnostic criteria to describe changes in different symptoms dimensions in the periMS period and that the latter are at least in part mediated by sex hormones.…”