Background and Rationale for Study: Estrogen and progesterone are female hormones that regulate the menstrual cycle and likely serve an important role in the regulation of mood. Premenstrual Syndrome (PMS) which affects 75% of healthy women is a cyclic pattern of mild dysphoria and physical discomfort that begin 1-2weeks pre-menses, and resolve by 2-3 days post-onset of menses. Up to 66% of women with bipolar disorder (BD) describe premenstrual mood changes that range from mild symptoms to severe worsening that require hospitalization. Therefore, the hormonal shifts of the menstrual cycle likely influence bipolar symptoms, but confirmatory research is lacking.

Study questions: The primary aims and hypotheses are to characterize bipolar mood symptoms throughout the menstrual cycle and to determine if women with BD have: 1) a) increased severity and persistence of depression and mania symptoms in the late luteal (premenstrual) vs early follicular phase, b) larger change in mood symptoms from the late luteal (premenstrual) to the early follicular phase, compared to healthy women, 2) more relapses, in the late luteal compared to the early follicular phase. The secondary aims are to determine: 1) frequency and severity of premenstrual dysphoric disorder (PMDD) type symptoms in bipolar women; 2) association between bipolar mood variability and a) menstrual phase, b) ovulatory vs anovulatory cycles, c) antimanic drug treatment.

Study Design: Women with BD (15 depressed, 15 euthymic), and 15 healthy women will enter the study. Over 3-months, subjects undergo monthly visits to assess mood and function, at the follicular and luteal phases. Ovulation is confirmed with: 1) urine dipstick tests to detect ovulation (LH surge) days8-14 from the onset of menses; 2) serum progesterone levels 7-days post-ovulation (LH surge). Subjects record their mood and physical symptoms on the daily self-report LifeChart and the Daily Rating Form.

Study Population: Women with Bipolar I or II Disorder, between ages 18-45. Primary Outcomes Measures: 1) a) mood severity - scores on the Structured Interview Guide for the Hamilton Depression Scale (SIGHADS) for depression, Mania Rating Scale (MRS) for mania/hypomania, and LifeChart mood ratings depression and mania/hypomania, for the late luteal and early follicular phases; b) persistence of symptoms - proportion of days with mild/moderate/severe depression or mania/hypomania. 2) Relapses - # bipolar episodes.

Inclusion Criteria:

• Ages 18-45;
• Bipolar Disorder (BD) I or II (DSM-IV criteria) must agrees to communication between PI and Psychiatrist;
• Healthy Control without Past or Current Major Depression, Psychotic Disorder, premenstrual syndrome or Premenstrual Dysphoric Disorder;
• 25-31day menstrual cycles;
• Minimum 6 menstrual cycles per year

Exclusion Criteria:

• Current DSM-IV Criteria Alcohol or Substance Abuse/Dependence;
• Pregnancy;
• Chronic Anovulation (<4 menstrual cycles/yr);
• Menopause (< 1menses in 1yr);
• Active thyroid disease;
• Hormonal Contraception

Community sample and outpatient psychiatric offices