Ovarian Suppression
Conditions
Keywords
Ovarian Suppression, Oral Contraceptives, Obese and Normal BMI
Brief summary
This study proposes a double blind randomized clinical trial to include normal weight and obese women who have normal ovulatory function at baseline; the investigators will randomize women to 2 widely used OCs and evaluate ovarian follicle development and circulating progesterone to assess ovarian suppression during OC use.
Detailed description
There is a large gap between lowest expected failure rates of about 1.5% and typical use failure rates of about 7% per year. This gap may be due to incorrect use or to decreased oral contraceptive (OC) effectiveness in population subgroups. Recent reports suggest greater OC failure among heavier women, particularly those using the lowest doses. The prevalence of obesity in the US population has recently increased to about 23% in women aged 20-29, peak years for OC use. OC physiology and effectiveness have not been evaluated in obese women.
Interventions
DRUGLow dose formulation
Participants are randomized to either Portia (levonorgestrel/ethinyl estradiol tablets, United States Pharmacopeia (USP)0.15 mg/0.03 mg or Lessina (levonorgestrel/ethinyl estradiol tablets, USP 0.1 mg/0.02 mg) for 3 months use. Dose formula contains 20 ug of ethinyl estradiol (EE) and 100 ug of levonorgestrel (LN) per tablet.
DRUGHigh dose formulation
Participants are randomized to either Portia (levonorgestrel/ethinyl estradiol tablets, United States Pharmacopeia (USP)0.15 mg/0.03 mg or Lessina (levonorgestrel/ethinyl estradiol tablets, USP 0.1 mg/0.02 mg) for 3 months use. Dose formula contains 30 ug of ethinyl estradiol (EE) and 150 ug of levonorgestrel (LN) per tablet.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 18-35 * Body Mass Index (BMI) 19-24.9 or 30-39.9 kg/m\^2 * Willing to take birth control pills for 3-4 months * Recent spontaneous pregnancy or cyclic menses
Exclusion criteria
* Contraindications to hormonal contraceptives * Oophorectomy/Polycystic ovary syndrome (PCOS) * Taken oral contraceptives to regulate menses recently * Weight reduction surgery * Used Depo-Provera within the last 12 months * Pregnant or currently breastfeeding * Desiring pregnancy within the next 4 months * Unable to make study visit commitment * Previous participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Up to 8 biweekly visits from start of OCP therapy | Perpendicular diameter, ethinyl estradiol, and progesterone values were used to create Hoogland Scores. Hoogland Scores were used to assess ovarian suppression during OC use. The Hoogland Score comprises 6 grades (Because of small numbers, grades 5 and 6 were combined): 1. no activity 2. potential activity 3. nonactive follicle-like structure 4. active follicle-like structure 5. luteinized unruptured follicle 6. ovulation Each participant received a score from 1-6 to indicate the level of ovarian suppression; total number of participants were tallied for each Hoogland score. |
Secondary
| Measure | Time frame |
|---|---|
| Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Screening (baseline) and follow-up 1 (exit) |
| Pharmacokinetics of 15 Obese Weight and 15 Normal Weight Women on Combined Oral Contraceptives. | 24 hours during week 3 of follow-up cycle |
Countries
United States
Participant flow
Recruitment details
Participant-related activities were conducted between July 2006-December 2008 in New York City
Pre-assignment details
Eligible women were aged 18-35 years with a recent history of regular, spontaneous menstrual cycles, and agreed to use an Oral Contraceptive Pill (OCP) for 3 to 4 months and undergo eight biweekly study visits during the third or fourth OCP cycle.
Participants by arm
| Arm | Count |
|---|---|
| Normal Weight Participants with a Body Mass Index (BMI) of 19-24.9. | 106 |
| Obese Participants with a Body Mass Index (BMI) of 30-39.9. | 75 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Early withdrawal | 14 | 11 |
| Overall Study | Lost to Follow-up | 8 | 12 |
Baseline characteristics
| Characteristic | Normal Weight | Obese | 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 | 106 Participants | 75 Participants | 181 Participants |
| Oral Contraceptive Pill Compliance Consistent Users | 96 Participants | 54 Participants | 150 Participants |
| Oral Contraceptive Pill Compliance Inconsistent Users | 4 Participants | 9 Participants | 13 Participants |
| Oral Contraceptive Pill Compliance Nonusers | 6 Participants | 12 Participants | 18 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 19 Participants | 19 Participants | 38 Participants |
| Race/Ethnicity, Customized Non-compliant OCP users (dropped from analysis) | 10 Participants | 21 Participants | 31 Participants |
| Race/Ethnicity, Customized Non-Hispanic African American | 30 Participants | 23 Participants | 53 Participants |
| Race/Ethnicity, Customized Non-Hispanic Asian | 14 Participants | 1 Participants | 15 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 33 Participants | 11 Participants | 44 Participants |
| Sex: Female, Male Female | 106 Participants | 75 Participants | 181 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 / 96 | 0 / 54 |
| serious Total, serious adverse events | 0 / 96 | 0 / 54 |
Outcome results
Primary
Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression.
Perpendicular diameter, ethinyl estradiol, and progesterone values were used to create Hoogland Scores. Hoogland Scores were used to assess ovarian suppression during OC use. The Hoogland Score comprises 6 grades (Because of small numbers, grades 5 and 6 were combined): 1. no activity 2. potential activity 3. nonactive follicle-like structure 4. active follicle-like structure 5. luteinized unruptured follicle 6. ovulation Each participant received a score from 1-6 to indicate the level of ovarian suppression; total number of participants were tallied for each Hoogland score.
Time frame: Up to 8 biweekly visits from start of OCP therapy
Population: Two hundred twenty-six women enrolled, 150 consistent OCP users were retained for the main analysis (96 normal weight and 54 obese).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Weight | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 4 - active follicle-like structure | 21 Participants |
| Normal Weight | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 5/6 - luteinization or ovulation | 4 Participants |
| Normal Weight | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 1 - no activity | 54 Participants |
| Normal Weight | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 2 - potential activity | 11 Participants |
| Normal Weight | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 3 - nonactive follicle-like structure | 6 Participants |
| Obese | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 3 - nonactive follicle-like structure | 6 Participants |
| Obese | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 4 - active follicle-like structure | 7 Participants |
| Obese | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 2 - potential activity | 12 Participants |
| Obese | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 5/6 - luteinization or ovulation | 1 Participants |
| Obese | Risk of Oral Contraceptive (OC) Failure Due to Less Contraceptive-mediated Ovarian Suppression. | Score of 1 - no activity | 28 Participants |
Secondary
Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure).
Time frame: Screening (baseline) and follow-up 1 (exit)
Population: We excluded participants who were not compliant with the study treatment (based on measuring serum hormone concentrations) from the analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Weight | Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Baseline Carbohydrate - Glucose | 87.2 mg/dL | Standard Deviation 8.6 |
| Normal Weight | Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Exit Carbohydrate - Glucose | 89.8 mg/dL | Standard Deviation 8.5 |
| Normal Weight | Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Baseline Lipid - Total Cholesterol | 171.4 mg/dL | Standard Deviation 25.9 |
| Normal Weight | Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Exit Lipid - Total Cholesterol | 172.3 mg/dL | Standard Deviation 27.3 |
| Obese | Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Exit Lipid - Total Cholesterol | 170.4 mg/dL | Standard Deviation 35.8 |
| Obese | Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Baseline Carbohydrate - Glucose | 90.2 mg/dL | Standard Deviation 7.1 |
| Obese | Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Baseline Lipid - Total Cholesterol | 177.0 mg/dL | Standard Deviation 27.2 |
| Obese | Lipid or Carbohydrate Metabolism in Obese Versus Normal Weight Oral Contraceptive (OC) Users at Baseline and Exit Visit (12-16 Weeks OC Exposure). | Exit Carbohydrate - Glucose | 92.7 mg/dL | Standard Deviation 10.5 |
Secondary
Pharmacokinetics of 15 Obese Weight and 15 Normal Weight Women on Combined Oral Contraceptives.
Time frame: 24 hours during week 3 of follow-up cycle
Population: Data were not available. No analysis performed.