Official Title: “Impact of Oral Contraceptives on GABA and Neurosteroids”

The purpose of this study is to investigate the effect of oral contraceptive pills (OCPs) on cortical GABA concentrations as measured by proton magnetic resonance spectroscopy (1H-MRS) in non-depressed, healthy menstruating women. A secondary aim is to determine the impact of OCP use on plasma and cerebral spinal fluid (CSF) levels of estradiol (E2) and progesterone, as well as neurosteroids such as pregnenolone, allopregnanolone, pregnanolone and 5 alpha-dihydroprogesterone (5α-DHP). We will assess the impact of OCPs on mood, controlling for previous history of affective disorders (excepting bipolar affective disorder or major depressive disorder with psychotic features). Mood symptoms will be measured throughout the study using the Daily Record of Severity of Problems (DRSP; Endicott & Harrison, 1990; Endicott et al., 2006), a self-rated symptom checklist.

Study Type: Observational

Study Design: Cohort, Prospective

Study Primary Completion Date: December 2011

Intervention(s) in this Clinical Trial

• Other: oral contraceptive pill
  • Daily administration of oral contraceptive pill for 3 months.

Arms, Groups and Cohorts in this Clinical Trial

• : Group 1
  • Women who have been taking any type of combined estrogen/progestin OCP for at least 3 months and would be willing to discontinue it for up to 2-3 menstrual cycles will be invited to participate in Group 1.
• : Group 2
  • Women who are not already on an OCP and would be willing to try one of two specific kinds: ethinylestradiol 35 ug and ethynodiol diacetate 1 mg or ethinyl estradiol 20 mcg and drospirenone 3mg for four months.

Primary Measures

• The purpose of this study is to investigate the effect of oral contraceptive pills (OCPs) on cortical GABA concentrations as measured by proton magnetic resonance spectroscopy (1H-MRS) in non-depressed, healthy menstruating women.
  • Time Frame: Outcomes will be measured at 2 points during each participants menstrual cycle.
    Safety Issue?: No

Secondary Measures

• To determine the impact of OCP use on plasma and cerebral spinal fluid (CSF) levels of estradiol (E2) and progesterone, as well as neurosteroids such as pregnenolone, allopregnanolone, pregnanolone and 5 alpha-dihydroprogesterone (5α-DHP).
  • Time Frame: Outcome will be assessed at 2 time points for each participant.
    Safety Issue?: No

Inclusion Criteria:

• Aged 18 - 42 years old and able to give voluntary written informed consent.
• Willing to complete a daily log of mood symptoms for 5 consecutive menstrual cycles.
• Be either taking a combined OCP for at least 3 months (Group 1), or be off of OCPs for at least 3 menstrual periods prior to beginning the study and be willing to go on OCPs for the study (Group 2).
• If Group 1, willing to stop OCP and use alternative non-steroidal birth control for up to 6 months.
• If Group 2, provide documentation of a normal PAP smear, pelvic and breast examination within the previous 12 months.
• If Group 2, have regular menstrual cycles 28 to 32 days in length. Each of the screening cycles must be ovulatory as confirmed by plasma progesterone levels of >3 ng/ml during the luteal phase.
• Negative pregnancy blood test at admission; negative urine pregnancy test on each MRS testing day.

Exclusion Criteria:

• Presence of any DSM-IV Axis I disorder, excepting possible mild to moderate PMS/PMDD, within the previous 12 months.
• Lifetime history of any psychotic disorder, including bipolar disorder.
• Meeting DSM-IV criteria for psychoactive substance (including nicotine) abuse/dependence within the preceding 6 months.
• A history of serious medical or neurological illness, including (but not limited to) major cardiovascular disease, hypertension (SBP > 140 mm Hg and DBP > 90 mm Hg), intracranial mass lesions, seizure disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease, unstable hematologic disease, gynecologic cancer and gallbladder disease, venous thromboembolism, and stroke.
• Diabetes if present with one other cardiovascular risk factor such as hypercholesterolemia or hypertension.
• Hypercholesterolemia if LDL > 160 mg/dl.
• Use of any psychotropic medication within the previous month.
• Alcohol consumption greater than 7 drinks/week.
• Current pregnancy or planning to become pregnant during the course of the study.
• Metallic implants.
• History of or suspected claustrophobias.
• Migraine headaches if > 35 yo.
• Weigh >300 lbs (the 4T magnet has a weight limit <300 lbs)

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 42 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Yale University

Overall Clinical Trial Officials and Contacts

C. Neill Epperson, M.D. Principal Investigator Yale University School of Medicine Department of Psychiatry  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00656318

Study ID Number: 0701002178

ClinicalTrials.gov Identifier: NCT00656318

Health Authority: United States: Institutional Review Board