Comparison of Serum Contraceptive Hormone Levels Between Normal Weight and Obese Users of the NuvaRing®

Study Overview
=================
Brief Summary
-----------------
There are over 60 million women of reproductive age in the U.S. and a majority of these women qualify as overweight or obese. Evidence suggests that there is an association between increased body weight and decreased contraceptive efficacy. Studies with the combined hormonal contraceptive patch (Evra®) and the subdermal contraceptive implant (Norplant®) demonstrate higher failure rates in heavier versus lighter women. Weight related differences in the effectiveness of NuvaRing® need further study. A single secondary analysis of pooled data from Phase III clinical trials of NuvaRing® noted no difference in pregnancy rates among women in the highest weight decile (>166#) versus the rest of the study population using the ring. (Westhoff, 2005) The finding of no difference, however, was influenced by too few obese subjects in the analysis which contributed to wide confidence limits. Additional studies are needed to explore how well the contraceptive ring functions to maintain effective serum steroid concentrations to suppress ovarian activity in obese women. This investigation focused on evaluating mean serum concentrations of hormones released in obese and normal weight women using the NuvaRing® . This study was a prospective clinical trial. Normal weight women are defined as women with a BMI 19-24.9 and obese women are those with a BMI 30-39.9. We recruited forty adult women interested in initiating the combined hormonal contraceptive ring to two months of use to complete analysis of at least 34 subjects (17 normal weight, 17 obese). We compared mean serum concentrations of ethinyl estradiol (E2) and etonogestrel (ENG) along with additional markers for ovarian suppression. These markers included sonographic evidence of follicular development and ovulation as well as circulating E2 levels which strongly correlate with follicular development and endometrial proliferation during the second month of NuvaRing® use. Assessment of these parameters will translated to understanding contraceptive-mediated suppression of ovarian function in these two groups. Subjects also logged patterns of ring use and bleeding patterns during the study period.

Official Title
-----------------
Comparison of Serum Contraceptive Hormone Levels Between Normal Weight and Obese Users of the NuvaRing®

Conditions
-----------------
Pharmacokinetics

Intervention / Treatment
-----------------
* Drug: NuvaRing
* Drug: NuvaRing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-35 yo Meet BMI requirements Weight stable English speaking Desire contraception History of regular menses with normal uterus and ovaries Medically eligible for combined hormonal contraception Tolerates phlebotomy/TVS Exclusion Criteria: Exclusion: Heavy smokers Users of medications that alter hormone levels

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

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1- Obese Women /Nuvaring<br>Obese subjects (BMI 30-39.9)received two contraceptive hormonal rings. During the second cycle of ring use, subjects returned to the study site for serial serum hormone measurements and transvaginal ultrasound twice weekly during four weeks of continuous use. | Drug: NuvaRing<br>* Obese subjects (BMI 30-39.9) will receive two contraceptive hormonal rings. During the second cycle of ring use, subjects will return to the study site for serial serum hormone measurements and transvaginal ultrasound twice weekly during four weeks of continuous use.<br>|
| Active Comparator: 2- Normal Weight / Nuvaring<br>Normal weight subjects (BMI 19-24.9) received two contraceptive hormonal rings. During the second cycle of ring use, subjects returned to the study site for serial serum hormone measurements and transvaginal ultrasound twice weekly during four weeks of continuous use. | Drug: NuvaRing<br>* Normal weight subjects will also receive two contraceptive hormonal rings. During the second cycle of ring use, subjects will return to the study site for serial serum hormone measurements and transvaginal ultrasound twice weekly during four weeks of continuous use.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Serum Concentrations of Etonogestrel and Ethinyl Estradiol | Serum concentrations were obtained from thirty-seven women completed follow-up. | Measurements at Week 3 and Week 6 continuous ring use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving a Maximum Follicle Diameter > 13mm During the 3 Weeks of Follow-up | Follicular development was minimal in both groups, with only five women achieving a maximum follicle diameter > 13mm at any time during the 3 weeks of follow-up (3 normal weight and 2 obese women). | continuous ring use, an average of 3 weeks | 
| Mean Endometrial Proliferation | The mean endometrial proliferation from week 1, week 2 and week3 | Transvaginal ultrasound measurements of endometrial proliferation will be completed over continuous ring use, an average of 3 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
contraceptive ring, obesity, pharmacokinetics, pharmacodynamics, Pharmacokinetics of the contraceptive ring in obese women.