Obesity and Oral Contraceptive Failure

Sponsor

Oregon Health and Science University (Other)

Overall Status

Terminated

CT.gov ID

NCT01944306

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Enrollment

Location

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Contraception Fetal Growth Retardation Infant, Small for Gestational Age Obesity

Study Design

Study Type:

Observational

Actual Enrollment :

26 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Prenatal Growth Programs Oral Contraceptive Metabolism and Effectiveness

Study Start Date :

Aug 1, 2013

Actual Primary Completion Date :

Apr 1, 2015

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Low birth-weight, obese
Low birth-weight, normal body weight
Normal birth-weight, obese
Normal birth-weight, normal body weight

Outcome Measures

Primary Outcome Measures

Measure pharmacokinetic parameters of oral contraceptives including drug clearance. [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 Outcome Measures

Measure levels of gonadotropins and ovarian hormones [Days 21-25 of oral contraceptive use]
To compare gonadotopin levels, average leutinizing hormone and follicle stimulating hormone levels measured for days 21-25 will be calculated. In addition, the follicle stimulating hormone/leutinizing hormone ratio will be calculated at each time point. The average levels of these measures will then be compared between the four groups of women using a student's t-test.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

age 18 to 35.
single progesterone level of 3 ng/mL or greater during the luteal phase (days 18 to

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.
smokers.
uncontrolled thyroid dysfunction.