Abstract

     Several lines of research suggest that reproductive-related hormonal events may affect the course of bipolar disorder in some women. However, data on associations between bipolar disorder and menarche, menstrual cycle, and menopause are mixed. This article reviews the literature on the potential effects of menarche, menstrual cycle, and menopause on bipolar disorder.

     A narrative review of published articles on bipolar disorder and menstrual cycle events was conducted. The primary outcome assessed was the impact of menarche, menstrual cycle and menopause on the course of bipolar illness. Databases searched were PubMed, Ovid, Scopus, PsycINFO, Medline, and Cochrane Libraries from inception to August 2021.

     Twenty-two studies were identified and included in the narrative synthesis. Research suggested that a subset of women with bipolar disorder are vulnerable to the impact of menstrual cycle events. Menarche seems to be associated with age at onset of bipolar illness especially in case of bipolar disorder type I and the specific age at menarche may predict some clinical features of the disorder. Menstrual cycle likely affects the course of bipolar disorder but the pattern of mood variability is not clear. Menopause appears to be not only a period of vulnerability to mood alteration, especially depressive episodes, and impairment of quality of life, but also a potential trigger of bipolar illness onset.

     The impact of menarche, menstrual cycle, and menopause on bipolar disorder is largely understudied. Preliminary evidence suggests that a subset of women with bipolar disorder may have their mood shifts affected by menstrual cycle events, with different patterns depending on the type of bipolar disorder also. Further researches are needed to deep the impact of menarche, menstrual cycle, and menopause on bipolar illness.

Introduction

     Bipolar disorder is a lifelong episodic illness characterized by fuctuations in mood state and energy (Grande et al. 2016). The course of bipolar disorder is associated with both inter-individual variation and heterogeneity between patients and can lead to functional, occupational, and cognitive impairments (Miller and Black 2020). Thus, over a lifetime any one patient may experience many forms of the disorder including depressive and manic or hypomanic episodes, mixed emotional states, and psychosis (Vieta et al. 2011). Bipolar disorders are classifed according to the longitudinal course: bipolar I disorder requires the occurrence of at least one fully syndromal lifetime manic episode, although depressive episodes are common; bipolar II disorder requires the occurrence of at least one hypomanic episode and one major depressive episode (American Psychiatric Association, 2013). The prevalence of bipolar illness is consistent across diverse cultures and ethnic groups, with an aggregate lifetime prevalence of 2.4% (Carvalho et al. 2020). Although bipolar disorder has an equal rate among men and women, some gender-related diferences have been found in the clinical features of the illness(Diforio and Jones 2010). Overall, it is reported that depressive episodes, rapid cycling, and mixed mania are more frequent in women than men (Altshuler et al. 2010; Marsh et al. 2012). Furthermore, there is accumulating evidence that bipolar disorder course is affected by reproductive-related hormonal events in women (Diforio and Jones 2010). Sex diferences have been hypothesized to be related to organizational and activational efects of sex hormones on the nervous system (Steiner et al. 2003). Gonadal steroids play a role in all stages of neurodevelopment, including neurogenesis, synaptogenesis, neural migration, growth, diferentiation, and cell survival (Payne 2003).

Results

     A fowchart of studies selected and included in the narrative review is provided in Fig. 1. From all databases combined, the initial search yielded 1229 results. After duplicates had been removed, 1197 articles remained. At title and abstract screening, 1028 articles were removed as they were not clinically relevant. A total of 169 articles were found to be suitable for inclusion in the full text screening. Full text screening of these articles eliminated 147 articles that did not meet the inclusion criteria. Twenty-two articles in total were included. Table 1, Table 2, and Table 3 list the studies that were included in the narrative synthesis.