Progression of female reproductive stages associated with bipolar illness exacerbation

Abstract

Objectives Late perimenopause and early postmenopause confer an increased risk of depression in the population, yet bipolar disorder mood course during these times remains unclear. Methods Clinic visits in 519 premenopausal, 116 perimenopausal including 13 women transitioning from perimenopause to postmenopause, and 133 postmenopausal women with bipolar disorder who received naturalistic treatment in the multisite STEP-BD study over 19.8±15.5 months were analyzed for mood state. History of postpartum and perimenstrual mood exacerbation and current hormone therapy were evaluated as potential mood predictors. Results A progression in female reproductive stage (premenopause, perimenopause, and postmenopausae) was significantly associated with percent of visits decreasing in euthymia (29.3%, 27.0%, 25.0%, respectively, p<0.05) decreasing in syndromal mood elevation (5.3%, 4.1%, and 3.0%, respectively, p<0.001), and increasing in subsyndromal symptoms (47.3%, 50.7%, and 52.7%, respectively, p = 0.05). Thirteen women transitioning from peri- to postmenopause had a significantly greater proportion of visits in syndromal depression (24.4%, p<0.0005) compared to premenopausal, perimenopausal and postmenopausal women, while depression in the latter three groups (18.1%, 18.1%, and 19.3%, respectively) did not differ. Perimenstrual and/or postpartum mood exacerbation, or hormone therapy did not significantly alter depression during perimenopause. Conclusions A progression in female reproductive stages was associated with bipolar illness exacerbation. A small number of women transitioning from perimenopause to postmenopause had significantly greater depression than other female reproductive groups. Euthymia and mood elevation decreased with progressing female reproductive stage. Menstrual cycle or postpartum mood exacerbation, or current hormone therapy use, was not associated with perimenopausal depression. Future studies, which include hormonal assessments, are needed to confirm these preliminary findings.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…For many women, stress and hormonal changes associated with the transition to menopause may increase or trigger mood symptoms 550, 551, 552. A post hoc analysis of the prospective Systematic Treatment Enhancement Program for Bipolar disorder (STEP‐BD) study showed increased rates of depressive, but not manic episodes during menopause transition 553.…”

Epigenetic regulation of estrogen-dependent memory

“…Estrogen loss at menopause (surgical or natural) can accelerate the onset of age-related cognitive decline (Sherwin, 2012; Hogervorst, 2013) and is associated with an increased risk of Alzheimer’s disease in women (reviewed in Maki, 2012). Furthermore, estrogens are associated with the symptomatology of bipolar disorder, anxiety disorders, depression, schizophrenia, migraine, catamenial epilepsy, and stroke (Walf and Frye, 2006; Milad et al, 2010; Begemann et al, 2012; Marsh et al, 2012; Reddy, 2013; Sohrabji and Williams, 2013). Although E 2 ’s neuroprotective, anti-depressant, mood-stabilizing, and memory enhancing properties (Walf and Frye, 2006; Sherwin and Henry, 2008; Kulkarni, 2009; Liu et al, 2010; Luine and Frankfurt, 2013) might support its use to reduce memory dysfunction in several brain disorders, estrogen therapy has been associated with potentially life-threatening side effects including breast and uterine cancer (Rossouw et al, 2002; Chlebowski et al, 2003).…”

Sexually Dimorphic, Developmental, and Chronobiological Behavioral Profiles of a Mouse Mania Model

“…Relative to men, women with BPDs display later disorder onset [39], tend to cycle more rapidly [40], experience a different subset of comorbid psychiatric disorders [41], and are more prone to mixed manic episodes [42]. Additionally, female reproductive state is associated with disorder presentation [43]. Equal prevalence but differential presentation between the sexes implies that though the genetic basis of BPDs remains constant between the sexes, these heritable underpinnings interact with female physiology differently than they do with male physiology to cause a sexually dimorphic phenotype.…”