Body Weight, Contraceptive Usage
Conditions
Keywords
Obesity, Body weight, Oral contraception, Efficacy
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.
Interventions
20 mcg EE/0.1 mg LNG cyclically
DRUGPortia
30 mcg EE/0.15 mg LNG cyclically
DRUGAviane
20 mcg EE/0.1 mg LNG continuously dosed
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| LNG AUC | post-randomization (4 months) | 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. |
| 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 |
Countries
United States
Participant flow
Recruitment details
A prospective cohort study was conducted at the Oregon Health & Science University (OHSU) in Portland, OR, from March 2006 to September 2007. Recruitment included print ads in local newspapers, flyers posted in the Center for Women's Health & other OHSU clinics and public places, and electronic postings to web sites such as Craig's List.
Participants by arm
| Arm | Count |
|---|---|
| Aviane and Aviane A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). 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) | 16 |
| Aviane and Portia A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). 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 | 15 |
| Total | 31 |
Baseline characteristics
| Characteristic | Aviane and Portia | Aviane and Aviane | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 16 Participants | 31 Participants |
| Age, Continuous | 27 years STANDARD_DEVIATION 4 | 30 years STANDARD_DEVIATION 4 | 29 years STANDARD_DEVIATION 4.7 |
| Region of Enrollment United States | 15 participants | 16 participants | 31 participants |
| Sex: Female, Male Female | 15 Participants | 16 Participants | 31 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 |
Outcome results
Primary
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).
Time frame: baseline (2 months) and post-randomization (4 months)
Population: One subject discontinued prior to the completion of the baseline studies in the Aviane/Aviane arm
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aviane & Aviane | LNG Steady State at Baseline and Then Post-randomization | LNG steady state levels at baseline | 3.82 ng/mL | Standard Deviation 1.28 |
| Aviane & Aviane | LNG Steady State at Baseline and Then Post-randomization | After randomization (4 months) | 3.01 ng/mL | Standard Deviation 0.19 |
| Aviane and Portia | LNG Steady State at Baseline and Then Post-randomization | LNG steady state levels at baseline | 3.13 ng/mL | Standard Deviation 0.87 |
| Aviane and Portia | LNG Steady State at Baseline and Then Post-randomization | After randomization (4 months) | 3.58 ng/mL | Standard Deviation 0.35 |
Secondary
EE Steady State After Randomization
Steady state levels of ethinyl estradiol (EE) post- randomization
Time frame: Post-randomiziation 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aviane & Aviane | EE Steady State After Randomization | 0.08 ng/mL | Standard Deviation 0.08 |
| Aviane and Portia | EE Steady State After Randomization | 0.11 ng/mL | Standard Deviation 0.01 |
Secondary
EE Steady State Baseline
Steady state levels of ethinyl estradiol (EE) at baseline (2 months)
Time frame: Baseline (2 months)
Population: One subject discontinued prior to the completion of the baseline cycle in the Aviane/Aviane arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aviane & Aviane | EE Steady State Baseline | 0.12 ng/mL | Standard Deviation 0.04 |
| Aviane and Portia | EE Steady State Baseline | 0.1 ng/mL | Standard Deviation 0.03 |
Secondary
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.
Time frame: post-randomization (4 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aviane & Aviane | LNG AUC | 412 hr*ng/mL | Standard Deviation 255 |
| Aviane and Portia | LNG AUC | 283 hr*ng/mL | Standard Deviation 130 |
Secondary
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.
Time frame: baseline (2 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aviane & Aviane | LNG AUC | 267 hr*ng/mL | Standard Deviation 115 |
| Aviane and Portia | LNG AUC | 199 hr*ng/mL | Standard Deviation 75 |