Continuous Oral Contraceptive Treatment in Premenstrual Dysphoric Disorder (PMDD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Susan Girdler, PhD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00927095
First received: June 22, 2009
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Premenstrual Dysphoric Disorder
Drug: low dose oral contraceptive (20 ug ethinyl estradiol + 3 mg drospirenone)
Drug: 20 ug ethinyl estradiol + 3 mg drospirenone
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Continuous OC Treatment in PMDD: Steroid Hormone Mechanisms

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • premenstrual symptom severity [ Time Frame: monthly ] [ Designated as safety issue: No ]

Estimated Enrollment: 58
Study Start Date: July 2008
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
continuous low dose oral contraceptive
Drug: low dose oral contraceptive (20 ug ethinyl estradiol + 3 mg drospirenone)
daily for three months
Other Name: Yaz
Active Comparator: 2
interrupted low dose oral contraceptive (21/7 platform)
Drug: 20 ug ethinyl estradiol + 3 mg drospirenone
daily for 21 days each month
Other Name: Yaz
Placebo Comparator: 3
continuous placebo
Drug: placebo
daily

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 52 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00927095

Locations
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Susan Girdler, PhD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Susan Girdler, PhD, Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00927095     History of Changes
Other Study ID Numbers: MH081837, MH081837
Study First Received: June 22, 2009
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
PMDD
Oral contraceptives
steroid hormones
neurosteroids

Additional relevant MeSH terms:
Premenstrual Syndrome
Menstruation Disturbances
Pathologic Processes
Contraceptive Agents
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Contraceptives, Oral
Estradiol
Polyestradiol phosphate
Ethinyl Estradiol
Drospirenone
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Aldosterone Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on July 24, 2014