Progression of female reproductive stages associated with bipolar illness exacerbation

Bipolar Disord. 2012 Aug;14(5):515-26. doi: 10.1111/j.1399-5618.2012.01026.x. Epub 2012 May 31.


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 Systematic Treatment Enhancement Program for Bipolar Disorder (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 postmenopause) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Affect
  • Aged
  • Aged, 80 and over
  • Aging / psychology*
  • Bipolar Disorder / physiopathology*
  • Depressive Disorder / physiopathology
  • Disease Progression
  • Estrogen Replacement Therapy
  • Female
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Perimenopause / psychology*
  • Postmenopause / psychology*
  • Premenopause / psychology
  • Premenstrual Syndrome
  • Prospective Studies