Dutasteride to Treat Women With Menstrually Related Mood Disorders

Phase 1

Completed

• Conditions: Premenstrual Syndrome; Depression; PMS; Healthy
• Interventions: Drug: Placebo oral capsule; Drug: Dutasteride

• Registration Number: NCT00082043
• Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary

This study will explore the effects of dutasteride on mood and the stress response across the menstrual cycle. Dutasteride blocks production of neurosteroids-hormones that help regulate the stress response systems. These systems may be disturbed in women with menstrually related mood disorders (MRMD). The effects of the drug will be compared in women with and without MRMD to determine how neurosteroids regulate mood and the stress response across the menstrual cycle. Dutasteride is approved by the Food and Drug Administration to treat benign prostatic hyperplasia (excess growth of the prostate gland) in men.

Menstruating women 30 to 45 years of age with and without MRMD may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, screening for symptoms of depression, and routine blood and urine tests. Participants are required to use barrier contraception (condoms or diaphragm) during the 3-month study and 6-month follow-up.

Participants undergo the following tests and procedures:

* Dutasteride or placebo treatment: Participants receive 1 month of dutasteride and 2 months of placebo. Neither the participants nor the investigators know when the subject is taking the active medication or the placebo.

* Biweekly follow-up visits: Every 2 weeks during the 3-month treatment period, patients come to the NIH Clinical Center to have blood drawn and to complete mood symptoms ratings.

* Monthly follow-up visits: Participants return to the Clinical Center once a month for 6 months after the end of the treatment period to monitor hormone levels and pregnancy status.

Detailed Description

Studies of premenstrual syndrome (PMS) to date have demonstrated that the syndrome represents an abnormal response to normal physiological events. Specifically patients with PMS experience a dysphoric mood state in response to normal luteal phase levels of progesterone and additionally fail to demonstrate the augmentation of the hypothalamic-pituitary-adrenal (HPA) axis normally seen in the luteal phase. A parsimonious explanation for the dysregulation of both mood and HPA axis function in PMS is that both are mediated by abnormal levels of or response to the progesterone neurosteriod metabolite, allopregnanolone. Both exposure to and withdrawal from allopregnanolone have been shown to precipitate adverse mood states in animal studies, presumably consequent to induced conformational changes in the GABA(A) receptor (increased alpha-4 subunit) that impair GABA receptor function. This impairment of GABA receptor function may also be associated with loss of restraint of HPA axis activity and hence may underlie the luteal phase increases in HPA activity in normal women. In this protocol, we propose to block conversion of progesterone to allopregnanolone in women with menstrual-related mood disorder (MRMD; equivalent in most reports to a severe form of PMS called premenstrual dysphoric disorder (PMDD)) and in normal (control) women. We will block progesterone metabolism (and hence exposure to allopregnanolone) with a newly approved 5 alpha-reductase inhibitor, dutasteride. We hypothesize the following: 1) Elimination of exposure to allopregnanolone in women with MRMD will eliminate dysphoric mood in the luteal phase; 2) Elimination of exposure of normal control women to allopregnanolone will eliminate the luteal phase enhancement of stimulated stress axis activity response.

These hypotheses, if confirmed, will increase the precision with which we can dissect the pathophysiological mechanisms involved in MRMD and in menstrual-related stress physiology.

In this protocol, our study objectives are as follows: Primary Objectives: 1) Determine whether suppression of neurosteroid synthesis will diminish mood symptoms in women with MRMD. 2) Determine if suppression of neurosteroid synthesis will eliminate luteal phase-related increases in stimulated HPA axis activity in control women. Secondary Objectives: 1) Determine whether differences in response to allopregnanolone account for the divergent effects of menstrual cycle phase on HPA axis activity in patients with MRMD and controls. 2) Determine if the Dex-CRH test, like the graded stressor treadmill test, can reveal the effects of menstrual cycle phase on HPA axis function.

Study Timeline

• Study Start: 2004-03-31
• Study First Submitted QC: 2004-04-27
• Study First Submitted: 2004-04-28
• Study First Posted: 2004-04-28
• Primary Completion: 2014-03-06
• Study Completion: 2014-03-06
• Status Verified: 2016-02-05
• Last Update Submitted: 2019-12-14
• Last Update Posted: 2019-12-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
2	Placebo oral capsule	Placebo oral capsule for two months
1	Dutasteride	Dutasteride 2.5 mg by mouth daily for one month

Primary Outcome Measures

Name	Time	Method
Rating Scale for Premenstrual Tension (PMTS); Daily symptom rating form (DRF); Visual Analogue Symptom (VAS) self-rating form.	Every 2 weeks for the PMTS; daily for the others.

Secondary Outcome Measures

Name	Time	Method
Neuroendocrine response to DEX/crh test; Beck Depression Inventory (BDI)	DEX/crf 2x second mth of tx, 1x during luteal ph & 1x during follicular ph.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike; 🇺🇸 Bethesda, Maryland, United States