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Menstrual Dysfunction Prior to Onset of Psychiatric Illness Is Reported More Commonly by Women With Bipolar Disorder Than by Women With Unipolar Depression and Healthy Controls

Hadine Joffe, M.D., M.Sc.; Deborah R. Kim, M.D.; John M. Foris, M.S.; Claudia F. Baldassano, M.D.; Laszlo Gyulai, M.D.; Cindy H. Hwang, B.A.; Wren L. McLaughlin, B.Sc.; Gary S. Sachs, M.D.; Michael E. Thase, M.D.; Bernard L. Harlow, Ph.D.; and Lee S. Cohen, M.D.

Background: Preliminary reports suggest that menstrual cycle irregularities occur more commonly in women with bipolar disorder and unipolar depression than in the general population. However, it is not always clear whether such abnormalities, reflecting disruption of the hypothalamic-pituitary-gonadal (HPG) axis, are caused by psychotropic treatments or associated with the disorder per se.

Method: The prevalence of early-onset (within the first 5 postmenarchal years) menstrual cycle dysfunction (menstrual cycle length unpredictable within 10 days or menstrual cycle length < 25 days or > 35 days) occurring before onset of psychiatric illness was compared between subjects with DSM-IV bipolar disorder participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and subjects with DSM-IV unipolar depression or no psychiatric illness participating in the Harvard Study of Moods and Cycles. Data from the Harvard Study of Moods and Cycles were gathered from September 1995 to September 1997, and data from STEP-BD were gathered from November 1999 to May 2001.

Results: Early-onset menstrual cycle dysfunction was reported to have occurred in 101/295 women with bipolar disorder (34.2%), 60/245 women with depression (24.5%), and 134/619 healthy controls (21.7%). Women with bipolar disorder were more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi2 = 16.58, p < .0001) and depressed women (chi2 = 6.08, p = .01), while depressed women were not more likely to have early-onset menstrual cycle dysfunction than healthy controls (chi2 = 0.81, p = .37).

Conclusions: Compared with healthy controls and women with unipolar depression, women with bipolar disorder retrospectively report early-onset menstrual dysfunction more commonly prior to onset of bipolar disorder. Future studies should evaluate potential abnormalities in the hypothalamic-pituitary-gonadal axis that are associated with bipolar disorder.

(J Clin Psychiatry 2006;67:297-304)

Received March 17, 2005; accepted August 9, 2005. From the Perinatal and Reproductive Psychiatry Clinical Research Program (Drs. Joffe and Cohen) and Bipolar Clinic and Research Program (Mss. Hwang and McLaughlin and Dr. Sachs), Massachusetts General Hospital, Harvard Medical School, Boston; the Mood and Anxiety Disorders Program, Hospital of the University of Pennsylvania, Philadelphia (Drs. Kim, Baldassano, and Gyulai); the Epidemiology Data Center, University of Pittsburgh Medical Center, Pittsburgh, Pa. (Mr. Foris); the University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic, Pittsburgh, Pa. (Dr. Thase); and the Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. (Dr. Harlow).

This study was funded by grants RO1-MH50013 and MH80001 from the National Institute of Mental Health, Bethesda, Md.

The authors report no additional financial or other relationship relevant to the subject matter of this article.

Corresponding author and reprints: Hadine Joffe, M.D., Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge St., 2nd Floor, Boston, MA 02114 (e-mail: