Oral Contraceptives and Body Mass Index

Phase 4

Completed

Brief Summary: The main hypothesis for this study is that increased Body Mass Index (BMI) alters oral contraceptive metabolism in a manner which results in decreased effectiveness in obese women.

Detailed Description: This study is being conducted to understand how effective oral hormonal birth control (the pill) is for women with high body mass index ("BMI" - the ratio of your height and weight BMI"). Previous studies of birth control traditionally do not include women above a certain BMI number, so safety and efficacy is not clearly understood in this population, yet the pill is still widely used in women with high BMI.

Reproductive-aged, ovulatory women of obese (BMI \>30 kg/m2), will be placed on oral contraceptives for 2 months, then randomized into two intervention arms for an additional 2 months. At several key time points, synthetic steroid pharmacokinetics, gonadotropins (LH, FSH) and ovarian hormone levels (estradiol, progesterone), ovarian follicular activity by ultrasound monitoring, and cervical mucus testing will be monitored.

Recruitment & Eligibility

Inclusion Criteria

Age 18-35
BMI > 30kg/m2
Proof of a normal breast and pelvic exam within last 9 months
Self reported normal menstrual periods (24-35 days)
Good general health
In the investigator's opinion, are subject's veins suitable the repeat blood draws dictated by study protocol
Single progesterone level during screening visit ≥ 3ng/mL
Hematocrit ≥ 36%

Exclusion Criteria

Contradictions to COCs (history of deep vein thrombosis,myocardial infection, uncontrolled hypertension, pulmonary embolus, diabetes with vascular changes, stroke, migraines with neurologic changes, breast cancer, impaired liver function, uncontrolled thyroid disease, hypersensitivity or allergy to birth control)
Smoker (must smoke 0 cigarettes)
Actively seeking/involved in a weight loss program
Currently pregnant/seeking pregnancy in the next 6 months
Currently breast-feeding
Past or current diagnosis of polycystic ovarian disease
Recent use of birth control (Depot medroxyprogesterone: 6 months, Progestin implants: 6 months, Oral contraceptives, patch or ring: 2 months, Hormone impregnated IUD: 6 months)
Currently taking medication that interferes with COC's (Rifampin, Carbamazepine, St. John's Wort)

Arm && Interventions

Group	Intervention	Description
All participants	All participants (Aviane)	A low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days).
Aviane and Portia	Portia	A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles
Aviane & Aviane	Aviane	A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)

Primary Outcome Measures

Name	Time	Method
LNG Steady State at Baseline and Then Post-randomization	baseline (2 months) and post-randomization (4 months)	The main goal is to test whether key pharmacokinetic parameters of levonordestrel (LNG) differ between obese women taking traditionally dosed OCs versus the interventional arms (i.e. using each obese subject as their own control).

Secondary Outcome Measures

Name	Time	Method
LNG AUC	baseline (2 months)	Baseline measurements of levonorgestrel AUC (on Aviane). Area under the curve at baseline for levonorgestrel. AUC was calculated from time zero to 168 hours and extrapolated to infinity from serial repeat sampling (0,0.5,1.1.5,2,3,4,6,8,12 hours and then single samples daily for 4 days between Cycles 1 and 2.
EE Steady State Baseline	Baseline (2 months)	Steady state levels of ethinyl estradiol (EE) at baseline (2 months)
EE Steady State After Randomization	Post-randomiziation 4 months	Steady state levels of ethinyl estradiol (EE) post- randomization