Effectiveness of Flutamide in Treating Women With Premenstrual Dysphoric Disorder

Androgen Hormones in PMDD

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

Study Overview

• Status: Completed
• Conditions: Premenstrual Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Flutamide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: B; Participants will take placebo flutamide	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.
Experimental: A; Participants will take flutamide	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.; Other Names: Eulexin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Premenstrual Symptoms as Measured by the Premenstrual Tension Scale (PMTS)	Low score on PMTS scale is 0 and high score is 40. Change score is calculated as PMTS score at month 1 or month 2 minus baseline PMTS score. Negative change score is a reduction in symptoms during treatment and positive change score is an increase in symptoms during treatment.	Measured at Months 1and 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Premenstrual Symptoms as Measured by the Daily Rating of Severity of Problems (DRSP) Scale	DRSP low score is 21 high score is 126. High score indicates more severe symptoms. Average score for the 4 days preceding menses was calculated for each subject in each cycle. Change score is calculated as DRSP score at month 1 or month 2 minus baseline DRSP score. Negative change score is a reduction in symptoms during treatment and positive change score is an increase in symptoms during treatment.	Measured at Months 1 and 2
Side Effect Burden Measured by Side Effect Questionnaire	The Side Effects Questionnaire is a measure of combined side effect burden, including a score for frequency (0-6), intensity (0-6) and interference with function (0-6). Low score is 0, high score is 18, High score represents greater severe side effect burden	Measured at Months 1 and 2
Premenstrual Symptoms as Measured by the Clinical Global Improvement Scale at Month 1 and Month 2	Scale range in 1-7. 1 is very much improved compared to baseline, 4 is no change compared to baseline, and 7 is very much worse compared to baseline.	Measured at Months 1 and 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Global Severity Scale	Scale range in 1-7. 1 is not at all ill, 4 is moderately ill, and 6 is severely ill and 7 is among the most extremely ill patients. Change score is calculated as Clinical Global Severity Scale score at the end of treatment month 1 or treatment month 2 minus baseline score. Negative change score is a reduction in symptoms during treatment and a positive change score is an increase in symptoms during treatment.	Measured at Month 1 and Month 2
Change in Premenstrual Symptoms as Measured by the Patient Global Premenstrual Symptoms as Measured by the Patient Global Improvement Scale at Month 1 and Month 2	Scale range in 1-7. 1 is very much improved, 4 is no change, and 7 is very much worse.	Measured at Month 1 and Month 2

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Institute of Mental Health (NIMH)

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 6, 2008
• First Submitted That Met QC Criteria: February 6, 2008
• First Posted (Estimate): February 11, 2008

Study Record Updates

• Last Update Posted (Actual): January 7, 2020
• Last Update Submitted That Met QC Criteria: December 18, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: PMS; PMDD; Premenstrual Dysphoric Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Mood Disorders; Depressive Disorder; Menstruation Disturbances; Premenstrual Dysphoric Disorder; Premenstrual Syndrome; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Androgen Antagonists; Flutamide
• Other Study ID Numbers: R34MH072878 (U.S. NIH Grant/Contract); DATR A5-ETPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No