Oral Contraceptives and Body Mass Index

Study Overview
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Brief Summary
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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
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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.

Official Title
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Improving Contraceptive Effectiveness in Obese Women

Conditions
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Body Weight, Contraceptive Usage

Intervention / Treatment
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* Drug: All participants (Aviane)
* Drug: Portia
* Drug: Aviane


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: All participants<br>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). | Drug: All participants (Aviane)<br>* 20 mcg EE/0.1 mg LNG cyclically<br>* Other names: Levonorgestrel and Ethinyl Estradiol;|
| Active Comparator: Aviane and Portia<br>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 | Drug: Portia<br>* 30 mcg EE/0.15 mg LNG cyclically<br>* Other names: Levonorgestrel and Ethinyl Estradiol;|
| Active Comparator: Aviane & Aviane<br>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) | Drug: Aviane<br>* 20 mcg EE/0.1 mg LNG continuously dosed<br>* Other names: Levonorgestrel and Ethinyl Estradiol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LNG Steady State at Baseline and Then Post-randomization | 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). | baseline (2 months) and post-randomization (4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LNG AUC | Area under the curve post-randomization for levonorgestrel. AUC was calculated and extrapolated using post randomization in single daily samples drawn during Cycle 4 days 20-26. Serial repeat sampling to obtain a detailed PK curve was not performed to obtain this AUC. Subjects could provide samples during these days at times convenient to them and PK software accounted for the time between when the drug was dosed versus when the sample was drawn. | post-randomization (4 months) | 
| LNG AUC | 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. | baseline (2 months) | 
| EE Steady State Baseline | Steady state levels of ethinyl estradiol (EE) at baseline (2 months) | Baseline (2 months) | 
| EE Steady State After Randomization | Steady state levels of ethinyl estradiol (EE) post- randomization | Post-randomiziation 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Body weight, Oral contraception, Efficacy