Obesity and Oral Contraceptive Failure
Obesity and Oral Contraceptive Failure
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.
Inclusion Criteria:

 -  age 18 to 35.

 -  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.

 -  smokers.

 -  uncontrolled thyroid dysfunction.