Abstract and Introduction
Objective: The aim of this study was to determine the effects of menstrual cycle phases (postmenses and premenses), self-report of premenstrual syndrome (PMS), late reproductive stages (LRS1 and LRS2), and early menopausal transition (EMT) stage (Stages of Reproductive Aging Workshop [STRAW]) on severity of five symptom groups.
Methods: A subset of Seattle Midlife Women's Health Study participants (n = 290) in either LRS1 or LRS2 or EMT (STRAW+10 criteria) provided daily symptom data for at least one full menstrual cycle during the first year of the study and reported current PMS. Symptom severity was rated (1–4, least to most severe) in the daily diary for five symptom groups (dysphoric mood, neuromuscular, somatic, vasomotor, and insomnia) identified earlier with the same sample (Maturitas 1996;25:1–10). A three-way analysis of variance was used to test for within- and between-participants effects on symptom severity.
Results: Stage had no effect on severity for any of the five symptom groups. Dysphoric mood and neuromuscular and somatic symptom severity (but not vasomotor or insomnia severity) differed significantly across menstrual cycle phases, increasing from postmenses to premenses. Current PMS and premenses cycle phase had significant interactive effects on dysphoric mood and neuromuscular symptoms, but there were no significant interaction effects on somatic, vasomotor, or insomnia symptom severity.
Conclusions: Dysphoric mood, neuromuscular, and somatic symptoms exhibit cyclicity and are influenced by current PMS. Late reproductive stages and EMT stage do not have significant effects on the five symptom groups. Vasomotor or insomnia symptoms do not exhibit significant cyclicity from postmenses to premenses and are not affected by current PMS. Future studies of symptom cyclicity and reproductive aging including daily symptom data across an entire menstrual cycle in samples including women in late menopausal transition stage are essential to capture the effects of both cyclicity and self-reported PMS to capture symptom severity reports at their peak.
Little is known about women's symptom experiences as they approach the menopausal transition stages, particularly during the late reproductive stage (LRS) of reproductive aging. As defined by the Stages of Reproductive Aging Workshop (STRAW+10 framework),[2,3] the LRS can be divided into substages or phases labeled −3b (the first phase of LRS) and −3a (the second phase of LRS). For the sake of clarity, in this article, these substages will be referred to as LRS1 (−3b) and LRS2 (−3a) to reflect progress toward final menstrual period (FMP). During LRS1, women continue menstruating regularly without change in cycle length. During LRS2, women also continue menstruating regularly but experience shortening or lengthening of their menstrual cycles by a few days with subtle changes in the amount of menstrual flow and/or in the number of days of flow.[3,4] After LRS2, women enter the early menopausal transition (EMT) stage when irregular cycles begin with increased variability in cycle length. Irregular cycles, as defined by Mitchell et l and validated by ReSTAGE, are persistent variability of 7 days or more between two consecutive menstrual cycles repeated within 12 months or within the next 10 cycles.
Evidence from a recent survey suggests that during the LRS, women begin to notice symptoms often associated with the menopausal transition, such as hot flashes, sleep changes, and mood symptoms. Women Living Better survey participants reported vasomotor symptoms (VMS) of hot flashes and night sweats before experiencing irregular cycles. The prevalence of these symptoms was higher during the menopausal transition stages than during the LRS. In addition, many of the same symptoms reported during the LRS and EMT occurred during the premenses and menses phases of the menstrual cycle among participants in other studies of the menopausal transition.[7,8]
Although women continue to menstruate during the LRS and EMT, little is known about cycle phase differences (CPDs) in symptom severity when comparing postmenses (follicular phase) with premenses (late luteal phase) during these stages. To date, there are no reports of symptom severity patterns from longitudinal studies of women studied daily during LRS and EMT during an entire menstrual cycle. Consequently, it is unclear whether women have cyclic symptoms in association with phases of the menstrual cycle during LRS or EMT and if symptom severity differs between menstrual cycle phases.
Menstrual CPD in symptoms is denoted by an increase in symptom severity from the follicular or postmenses phase to the late luteal or premenses phase with a decrease after menses. Many different labels have been used to describe this type of symptom pattern such as molimina, perimenstrual symptoms, premenstrual syndrome (PMS),[10,11] premenstrual magnification (PMM), and premenstrual dysphoric disorder, each with different criteria.
Few studies of cyclic symptoms in midlife women, especially those in LRS or EMT, have been reported. Woods et al found that women who were screened for PMS symptom patterns before they reached 40 years of age continued to experience the PMS symptom pattern documented in a daily symptom diary after they reached 40 years of age. Freeman et al with the Penn Ovarian Aging Study (POAS) found that fewer women reported the PMS symptom pattern after they reached 40 years of age, although these women continued to report PMS symptoms including hot flashes, depressed mood, decreased libido, and poor sleep during the menopausal transition stages.[13–16] Dennerstein et al also identified an association between women's prior history of premenstrual complaints and negative mood symptoms experienced over 6 years of follow-up during the menopausal transition by the Melbourne Midlife Women's Health Project (MMWHP) participants.
Investigators for the POAS and the MMWHP relied on women's retrospective reports of PMS before the onset of the menopausal transition. For example, Freeman assessed PMS with two questions inquiring about irritability, mood swings, and emotional distress and the degree to which they interfered with daily activities. Dennerstein et al assessed premenstrual complaints by inquiring about physical or psychological changes women considered problematic, causing personal distress, and affecting work or relationships. The cyclic nature of these symptoms was not confirmed with daily prospective measures of postmenses and premenses symptom severity in these studies.
To date, there are no published reports of CPDs in symptom severity during the LRS and EMT using prospective symptom recordings. In addition, there are no published reports comparing self-reports of current PMS by midlife women with prospective reports of cyclic symptoms.
Prospective data provided by women during LRS and EMT could illuminate the relationship between symptoms that vary by menstrual cycle phase and by reproductive aging stages. Our goal was to enhance understanding of this period of a woman's reproductive aging by considering the effects of the menstrual cycle, self-reports of current PMS, and menopausal transition stages on severity of the five symptom groups commonly reported by midlife women.
The research questions were as follows:
Does symptom severity of each symptom group (dysphoric mood, vasomotor, somatic, neuromuscular, insomnia) differ when accounting for stages of reproductive aging (late reproductive and EMT stages [LRS1, LRS2, and EMT]), menstrual cycle phase (follicular/postmenses and late luteal/premenses menstrual cycle phases), and self-report of current PMS?
Is there an interactive effect between reproductive aging stage (LRS1, LRS2, and EMT), menstrual cycle phase (postmenses and premenses), and self-report of current PMS on symptom severity for each symptom group?
Menopause. 2022;21(11):1269-1278. © 2022 The North American Menopause Society