Continuous Oral Contraceptive Treatment in Premenstrual Dysphoric Disorder (PMDD)

Premenstrual Dysphoric Disorder Clinical Trial

— PMDD  

Official title:

Continuous OC Treatment in PMDD: Steroid Hormone Mechanisms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00927095
• Other study ID #: MH081837
• Secondary ID: MH081837
• Status: Completed
• Phase: Phase 4
• First received: June 22, 2009
• Last updated: June 11, 2015
• Start date: July 2008
• Est. completion date: July 2014

Study information

• Verified date: June 2015
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare a low dose oral contraceptive (OC) given continuously (every day for three months) with the same low dose oral contraceptive given in an interrupted regimen (one week of inactive placebo pills each month) and with continuous placebo (inactive placebo given every day for three months). The primary hypothesis is that continuous OC will be significantly more effective in reducing premenstrual symptoms compared with either the interrupted OC or continuous placebo.

Description:

Premenstrual Dysphoric Disorder (PMDD) describes the cyclic appearance of affective symptoms and resultant impairment during the luteal phase of the menstrual cycle. The objective of this trial is to determine if extended oral contraceptive (OC) regimens with eliminated pill-free intervals will successfully prevent the expression of PMDD symptoms. The central hypothesis of this application is that continuous administration of OCs will minimize the destabilizing effects of changing reproductive steroid levels and prevent PMDD symptom emergence. The cause of PMDD is unknown, the morbidity substantial, and the identified treatments limited in their effectiveness, since 40% of PMDD women are non-responders to elective serotonin re-uptake inhibitors (SSRIs). Earlier controlled studies of OCs to treat PMDD failed to find OCs superior to placebo using the traditional 21/7 platform (21 active pills followed by a 7 day pill-free interval (PFI)). Two recent trials of a low dose OC using a 24/4 platform did report greater reductions in premenstrual symptoms relative to placebo, presumably due to the shortened PFI. Despite the apparent efficacy of the 3-day extended dosing of this OC, the placebo response rate was substantial in these studies, resulting in a low effect size. Moreover, no steroid hormone levels were examined in these prior studies. In the absence of hormonal data, inferences about the mechanism of efficacy of extended OCs must remain speculative and untested.

Our proposed research will addresses the critical role of hormonal change in the precipitation of PMDD symptoms before and after treatment with a continuous OC regimen, an interrupted OC regimen (21/7 platform) and continuous placebo. This study will also permit us to examine the role of neurosteroids in PMDD. While acting acutely as anxiolytic positive modulators of the gamma-aminobutyric acid A (GABAA) receptor, these neurosteroids may paradoxically reduce the response of the GABAA receptor and cause irritability (in rats) following either extended exposure or withdrawal. Further, our prior research suggests that elevated levels of or changes in peripheral neurosteroid levels are associated with dysphoric mood symptoms in women with PMDD. Our hypothesis is that changes in neurosteroids modulate symptom severity rather than appearance in PMDD. The results of our study will suggest therapeutic targets and will inform future studies of both PMDD and related affective disorders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 52 Years

Eligibility

Inclusion Criteria:

• meets prospective criteria for PMDD, AND

• English speaking and reading skills.

Exclusion Criteria:

• current psychiatric disorder other than PMDD,

• history of venous thromboembolism,

• over 35 years of age and obese,

• uncontrolled hypertension or end-organ vascular disease,

• diabetes,

• migraine headache with aura,

• breastfeeding or pregnant,

• cigarette smoking,

• family history of premenopausal breast cancer or breast cancer in more than one first degree relative,

• elevated serum potassium levels, use of prescription medications (except stable thyroid supplementation),

• irregular menstrual cycles, OR

• history of: endometriosis, hepatic disease, breast carcinoma, pulmonary embolism or phlebothrombosis, malignant melanoma, cholecystitis or pancreatitis.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Premenstrual Dysphoric Disorder

Intervention

Drug:
• low dose oral contraceptive (20 ug ethinyl estradiol + 3 mg drospirenone)
daily for three months
• 20 ug ethinyl estradiol + 3 mg drospirenone
daily for 21 days each month
• placebo
daily

Locations

Country	Name	City	State
United States	University of North Carolina	Chapel Hill	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	premenstrual symptom severity		monthly	No