Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu
Trial record 96 of 102 for:    DROSPIRENONE AND ETHINYL ESTRADIOL

Continuous Oral Contraceptive Treatment in Premenstrual Dysphoric Disorder (PMDD) (PMDD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00927095
Recruitment Status : Completed
First Posted : June 24, 2009
Results First Posted : August 24, 2016
Last Update Posted : August 24, 2016
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Susan Girdler, PhD, University of North Carolina, Chapel Hill

Brief 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.

Condition or disease Intervention/treatment Phase
Premenstrual Dysphoric Disorder Drug: Continuous OC (EE/DROS) Drug: Intermittent OC (EE/DROS) Drug: placebo Phase 4

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Continuous OC Treatment in PMDD: Steroid Hormone Mechanisms
Study Start Date : July 2008
Actual Primary Completion Date : July 2014
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Continuous OC (EE/DROS)
Continuous daily oral drospirenone (DROS; 3mg) + ethinyl estradiol (EE; 20ug)
Drug: Continuous OC (EE/DROS)
Continuous EE(20ug)+DROS(3mg) daily for 3 months
Other Name: Yaz

Active Comparator: Intermittent OC (EE/DROS)
Interrupted (21 days active - 7 days placebo) oral DROS (20ug)/EE(3mg)
Drug: Intermittent OC (EE/DROS)
Intermittent EE(20ug)+DROS(3mg) daily for 21 days each month
Other Name: Yaz

Placebo Comparator: Placebo
Continuous daily oral placebo
Drug: placebo
daily placebo
Other Name: oral placebo

Primary Outcome Measures :
  1. Pre-Post Change in Premenstrual Symptom Severity [ Time Frame: monthly ]
    Pre-post change (pre minus post) in mean premenstrual week severity of the worst emotional symptom as measured using the Daily Record of Severity of Problems items 1-8. Worst symptom for each individual was defined as the symptom in the baseline month demonstrating the highest mean severity during the premenstrual week. Mean premenstrual week severity scores were calculated to correspond to mean ratings; therefore, the mean premenstrual severity values ranged as follows: 1=Not at All, 2=Minimal, 3=Mild, 4=Moderate, 5=Severe, 6=Extreme. The change variable presented here is calculated as follows: "mean rating on the individual's worst symptom during the premenstrual week at baseline" minus "mean rating during the premenstrual week during the last on-treatment cycle". Therefore, higher values on this outcome variable correspond to greater reductions in premenstrual symptoms across the trial.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 52 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00927095

Layout table for location information
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
National Institute of Mental Health (NIMH)
Layout table for investigator information
Principal Investigator: Susan Girdler, PhD University of North Carolina, Chapel Hill

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Susan Girdler, PhD, Professor, University of North Carolina, Chapel Hill Identifier: NCT00927095    
Other Study ID Numbers: MH081837
R01MH081837 ( U.S. NIH Grant/Contract )
First Posted: June 24, 2009    Key Record Dates
Results First Posted: August 24, 2016
Last Update Posted: August 24, 2016
Last Verified: July 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Susan Girdler, PhD, University of North Carolina, Chapel Hill:
Oral contraceptives
steroid hormones
Additional relevant MeSH terms:
Layout table for MeSH terms
Premenstrual Dysphoric Disorder
Premenstrual Syndrome
Menstruation Disturbances
Pathologic Processes
Depressive Disorder
Mood Disorders
Mental Disorders
Contraceptive Agents
Contraceptives, Oral
Physiological Effects of Drugs
Reproductive Control Agents
Contraceptive Agents, Female