Prenatal Growth Programs Oral Contraceptive Metabolism and Effectiveness
Trial Snapshot
- Phase
- Not Applicable
- Status
- Terminated
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Measure pharmacokinetic parameters of oral contraceptives including drug clearance.
Study Overview
Brief Summary
Contraceptive failure is the primary cause of unintended pregnancy in the United States. With obesity rates at epidemic proportions, any association between obesity and strategies that prevent undesired pregnancies constitutes a significant public health and economic concern. Evidence from recent epidemiological studies and our preliminary data (sub-therapeutic levels of steroid hormones due to drug clearance and half-life) suggest that obesity reduces oral contraceptive efficacy. Furthermore, preliminary analysis suggested that a sub-group of obese women, defined by their own birth weight, are at higher risk of contraceptive failure. Further studies are necessary to investigate whether birth weight, a surrogate marker of in utero growth restriction, is a useful diagnostic marker for the identification of women prone to contraceptive failure. Such an understanding is critical to finding a contraceptive strategy with better efficacy for these women.
The overall goal of this project is to test pharmacokinetics of oral contraceptive agents in obese women with low birth weight and compare to obese women with normal birth weight. The main hypothesis for this proposal is that an adverse in utero environment programs the expression and function of enzymes and transporters that underlie pharmacokinetics of oral contraceptives, and leads to contraceptive failure.
Reproductive-aged, ovulatory women of obese BMI >30 kg/m2 with normal birth weight (5.5-8 lbs; n=10) and low birth weight (<5.5 lbs; n=10), will be placed on oral contraceptives for 1 month. At several key time points, synthetic steroid pharmacokinetics, gonadotropins (luteinizing hormone, follicle-stimulating hormone) and ovarian hormone levels (estradiol, progesterone) will be monitored.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 35 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •age 18 to
- •single progesterone level of 3 ng/mL or greater during the luteal phase (days 18 to 25) in the menstrual cycle prior to dosing with oral contraceptives.
Exclusion Criteria
- •absolute/relative contraindications to ethinyl estradiol and levonorgestrel.
- •impaired liver function.
- •history of deep venous thrombosis.
- •hypertension (> 140/90).
- •diabetes with vascular changes.
- •migraines with aura or neurological changes.
- •history of myocardial infarction, pulmonary embolus, stroke or breast cancer.
- •anemia (hematocrit < 36%).
- •actively seeking or involved in a weight loss program (must be weight stable)
- •pregnancy, breastfeeding, or seeking pregnancy.
- •diagnosis of Polycystic Ovarian Syndrome.
- •recent (4 week) use of hormonal contraceptives (patch or ring included), intrauterine, or implantable hormonal contraception.
- •DepoProvera use within six months.
- •current use of drugs that interfere with metabolism of sex steroids.
- •uncontrolled thyroid dysfunction.
Outcomes
Primary Outcomes
Measure pharmacokinetic parameters of oral contraceptives including drug clearance.
Time Frame: on day 21 of oral contraceptive use
Serum concentration-time data for each subject will be analyzed using a non-compartmental model assumption. Serum concentrations below the lower limit of quantitation (LLOQ) at the beginning and end of the profile will be set to zero. Serum concentration-time profiles will be summarized using descriptive statistics and graphical display. Student t-tests will be used to test whether the average values of each of the pharmacokinetic parameters, including free concentrations, differ between the four groups of women.
Secondary Outcomes
- Measure levels of gonadotropins and ovarian hormones(Days 21-25 of oral contraceptive use)