Treatment of Menstrually Related Disorders With Continuous v. Interrupted Oral Contraceptives

Phase 2

Terminated

Conditions: Depression
Premenstrual Dysphoric Disorder
PMDD
Premenstrual Syndrome
PMS

Interventions: Drug: Ethinyl Estradiol/Drospirenone
Drug: Placebo
Drug: CDB 2914

Registration Number: NCT00089414

Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary: This study will determine whether uninterrupted treatment with birth control pills over several menstrual cycles prevents severe premenstrual syndrome (PMDD).

Previous studies have shown that the hormones estrogen and progesterone regulate mood in women with MRMD. This study will use various treatment regimens with birth control pills and placebo (sugar pill) to clarify the relationships among estrogen and progesterone, the menstrual cycle, and mood.

Healthy women between 18 and 45 years of age who menstruate may be eligible for this 15-week study. Candidates are screened with a physical examination, blood and urine tests, an electrocardiogram, and 3 months of symptoms ratings to confirm MRMD.

Participants are randomly assigned to one of three treatment groups. Group 1 takes a birth control pill every day and on three occasions takes a placebo capsule. Group 2 takes a birth control pill most but not all days and on three occasions takes a placebo capsule. Group 3 takes a birth control pill every day and on three occasions takes another medication called CDB-2914 that causes menstrual bleeding to occur.

Participants come to the NIH clinic every other week for blood tests and measurement of vital signs (blood pressure, pulse, and temperature) and to complete symptoms ratings scales. Subjects who develop breakthrough bleeding (menstruation earlier than expected) will have a transvaginal ultrasound. For this procedure, a probe is inserted into the vagina for about 10 minutes. The probe gives off and receives sound waves that can be used to form a picture of the endometrium (lining of the uterus).

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Detailed Description: Results from previous protocols (#90-M-0088 and 92-M-0174) have demonstrated that women with menstrually-related mood disorder (MRMD), but not women lacking this disorder, experience mood deterioration within approximately one to two weeks after exposure to either estradiol or progesterone in the context of gonadal suppression (induced by use of the depot gonadotropin releasing hormone agonist leuprolide acetate). Preliminary results of protocol 00-M-0103 suggest that this hormone-induced depression occurs consequent to changes in gonadal steroid levels and not to simple exposure to basal levels above a critical threshold. Additionally, continued administration of hormone for three months resulted in no further symptoms subsequent to the initial precipitated episode. These data suggest the potential therapeutic benefit of extended oral contraceptive (OC) regimens with reduced pill-free intervals in MRMD to minimize the mood destabilizing effects of changing hormone levels. In this protocol we examine whether the effects of 15 weeks of continuous oral contraceptive administration causes a remission of symptoms in women with MRMD.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Ethinyl Estradiol/Drospirenone	Treatment arm # 1 consists of the continuous administration of Yasmin oral contraceptive (a combination of 30 µg of ethinyl estradiol and 3 mg of drospirenone) for 15 weeks starting on day 2 to 5 of the first menstrual cycle.
2	Ethinyl Estradiol/Drospirenone	Treatment arm # 2 (interrupted Yasmin administration) will be identical to arm # 1 with the exception that the continuous administration of Yasmin will be interrupted by the substitution of placebo for Yasmin for one week during weeks 3, 8, and 14 of the study. The women participating in this treatment arm will experience episodes of menstruation after Yasmin withdrawal (when they are on placebo).
2	Placebo	Treatment arm # 2 (interrupted Yasmin administration) will be identical to arm # 1 with the exception that the continuous administration of Yasmin will be interrupted by the substitution of placebo for Yasmin for one week during weeks 3, 8, and 14 of the study. The women participating in this treatment arm will experience episodes of menstruation after Yasmin withdrawal (when they are on placebo).
3	Ethinyl Estradiol/Drospirenone	Yasmin oral contraceptive; CDB 2914 progesterone antagonist. Treatment arm # 3 is identical to treatment arm # 1 with the exception that the continuous administration of Yasmin will also include the administration of progesterone antagonist CDB-2914 during weeks 3, 8, and 14. Menses is anticipated to occur within 2-3 days of CDB-2914 administration. Women in treatment arms # 3 and # 1 will be exposed to continuous levels of Yasmin, but due to the local effects of the progesterone antagonist on the endometrium, women in arm # 3 will experience menses.
3	CDB 2914	Yasmin oral contraceptive; CDB 2914 progesterone antagonist. Treatment arm # 3 is identical to treatment arm # 1 with the exception that the continuous administration of Yasmin will also include the administration of progesterone antagonist CDB-2914 during weeks 3, 8, and 14. Menses is anticipated to occur within 2-3 days of CDB-2914 administration. Women in treatment arms # 3 and # 1 will be exposed to continuous levels of Yasmin, but due to the local effects of the progesterone antagonist on the endometrium, women in arm # 3 will experience menses.

Primary Outcome Measures

Name	Time	Method
Change in Premenstrual Tension Syndrome Scale (PMTS) Factors Associated With Premenstrual Symptoms.	Every 2 weeks for 3 months	The PMTS observer scales assess symptoms in ten different domains including irritability-hostility; tension; efficiency; dysphoria; moodiness; motor coordination; mental-cognitive functioning; eating habits; sexual drive and activity; physical symptoms and social impairment. They have been used to measure premenstrual symptom severity and response to treatment in several clinical trials and prevalence studies. Score ranges from no symptoms to severe symptoms on a scale of 0 to 6, with 0 being no symptoms and 6 being severely symptomatic.

Secondary Outcome Measures

Name	Time	Method
Change in Clinical Global Impression Scale (CGI) Factors Associated With Premenstrual Symptoms.	Every 2 wks for 3 months	The CGI was developed for use in NIMH-sponsored clinical trials to provide a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication.1 The CGI provides an overall clinician-determined summary measure that takes into account all available information, including a knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function. The CGI actually comprises two companion one-item measures evaluating the following: (a) severity of psychopathology from 1 to 7 and (b) change from the initiation of treatment on a similar seven-point scale, with 1 being normal/more improved and 7 being severe/worse.
Change in Beck Depression Inventory (BDI) Factors Associated With Premenstrual Symptoms	Every 2 weeks for 3 months	The Beck Depression Inventory (BDI)is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. Total scores are interpreted per these ranges: 0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression.