Continuous Oral Contraceptive Treatment in Premenstrual Dysphoric Disorder (PMDD)
| Status: | Completed |
|---|---|
| Conditions: | Women's Studies |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 18 - 52 |
| Updated: | 3/1/2014 |
| Start Date: | July 2008 |
| End Date: | May 2014 |
| Contact: | Susan Girdler, PhD |
| Email: | susan_girdler@med.unc.edu |
| Phone: | 919-966-2544 |
Continuous OC Treatment in PMDD: Steroid Hormone Mechanisms
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.
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.
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.
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.
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.
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