Effectiveness of Flutamide in Treating Women With Premenstrual Dysphoric Disorder

Official Title: “Androgen Hormones in PMDD”

This study will evaluate the effectiveness of flutamide in reducing symptoms of premenstrual dysphoric disorder.

Premenstrual dysphoric disorder (PMDD) is a condition that affects about 5% of menstruating women. Women with PMDD experience serious emotional and physical disturbances, which may include depression, tension, irritability, anger, anxiety, and sleep and appetite problems.

Symptoms of PMDD are directly linked with the menstrual cycle, generally beginning in the latter half of the cycle and ending around the start of the next cycle. If left unmanaged, PMDD may interfere with a woman's ability to carry out normal day-to-day functioning.

Current treatments for PMDD include medications, psychotherapy, and nutritional modifications. Flutamide, a medication that blocks the action of testosterone and other mood-influencing hormones, may be helpful in alleviating symptoms of PMDD. This study will evaluate the effectiveness of flutamide in reducing symptoms of premenstrual dysphoric disorder.

This two-phase study will last a total of 4 months and will include 7 study visits. Phase 1 will last 2 months and will include Visits 1 through 3. During Phase 1, participants will keep a daily record of symptoms, participate in a diagnostic interview, and undergo a medical history review, a physical exam, and screening laboratory tests. Eligible participants will then enter Phase 2, the treatment phase of the study.

During the treatment phase, participants will be randomly assigned to take flutamide or placebo for 2 months. Study visits will occur every 2 weeks and will include Visits 4 through 7. These visits will include discussion of side effects, symptom rating, and laboratory tests to check for pregnancy and any side effects related to liver function, blood counts, or blood chemistry. At the end of treatment with flutamide or placebo, participants will have the option of receiving treatment with sertraline, an antidepressant known to be effective for many women with PMDD. Sertraline will be given during the 2 premenstrual weeks for two cycles. If participants have already unsuccessfully tried sertraline for PMDD treatment, an alternative treatment can be attempted.

Intervention(s) in this Clinical Trial

• Drug: Flutamide
  • Participants will take one 125-mg flutamide capsule twice a day for two menstrual cycles. If a participant is unable to tolerate a twice-daily dose due to side effects, the dose will be reduced to one capsule per day.
• Drug: Placebo
  • Participants will take a lactose capsule twice a day for two menstrual cycles. If a participant is unable to tolerate a twice-daily dose due to side effects, the dose will be reduced to one capsule per day.

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: B
  • Participants will take placebo flutamide
• Experimental: A
  • Participants will take flutamide

Primary Measures

• Premenstrual Tension Scale (PMTS)
  • Time Frame: Measured at Months 2 and 4
    Safety Issue?: No

Secondary Measures

• Daily Rating of Severity of Problems (DRSP) Scale
  • Time Frame: Measured at Months 2 and 4
    Safety Issue?: No
• Side Effect Questionnaire
  • Time Frame: Measured at Months 2 and 4
    Safety Issue?: Yes
• Clinical Global Improvement Scale
  • Time Frame: Measured at Months 2 and 4
    Safety Issue?: No

Inclusion Criteria:

• Meets DSM-IV criteria for PMDD by history
• Regular menstrual cycles that are 25 to 35 days in length during the year prior to study entry
• Willing to use barrier methods of birth control during the study if sexually active
• If engaged in psychotherapy for at least 3 months before study entry, participation will be allowed if the intensity of psychotherapy remains the same during the study
• Normal PAP and physical exam, including pelvic exam, within the 1 year prior to study entry

Exclusion Criteria:

• Use of oral contraceptives or other exogenous hormone preparations within the 3 months prior to study entry
• Suicide attempt or severe suicidal ideation within the 2 years prior to study entry
• History of any psychotic disorder or bipolar disorder
• Substance abuse, except nicotine, within the 6 months prior to study entry
• Use of pharmacological treatment for PMDD symptoms (e.g., antidepressants, hormones, gonadotropin-releasing hormone agonists, anxiolytics, calcium, herbal preparations, diuretics) within the 3 months prior to study entry
• Daily use of psychotropic or anticonvulsant medications within the 3 months prior to study entry
• Use of sleeping pills more than once per week
• Consumption of more than 50 ounces of alcohol per week
• Pregnant or breastfeeding
• Hepatic, renal, autoimmune, or chronic inflammatory disease
• Seizure disorder
• Inability to read or follow instructions in English

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 48 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: National Institute of Mental Health (NIMH) NIH

Overall Clinical Trial Officials and Contacts

Margaret Altemus, MD Principal Investigator Weill Medical College of Cornell University  

Overall Contact: Diane Engel, LMSW 212-746-3759 die2001@med.cornell.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00611923

Study ID Number: R34 MH072878

ClinicalTrials.gov Identifier: NCT00611923

Health Authority: United States: Federal Government