Clinical trial NCT00710606: Comparison of Serum Contraceptive Hormone Levels Between Normal Weight and Obese Users of the NuvaRing®
Official title: Comparison of Serum Contraceptive Hormone Levels Between Normal Weight and Obese Users of the NuvaRing®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pharmacokinetics
Keywords: contraceptive ring
obesity
pharmacokinetics
pharmacodynamics
Pharmacokinetics of the contraceptive ring in obese women.
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Organon
First posted: 2008-07-04
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

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.


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

Primary outcomes:
measure: Mean Serum Concentrations of Etonogestrel and Ethinyl Estradiol
timeFrame: Measurements at Week 3 and Week 6 continuous ring use
Secondary outcomes:
measure: Number of Participants Achieving a Maximum Follicle Diameter > 13mm During the 3 Weeks of Follow-up
timeFrame: continuous ring use, an average of 3 weeks
measure: Mean Endometrial Proliferation
timeFrame: Transvaginal ultrasound measurements of endometrial proliferation will be completed over continuous ring use, an average of 3 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Division of Family Planning and Preventive Services
state: New York
Study officials:
affiliation: Columbia University
name: Carolyn Westhoff, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gu S, Sivin I, Du M, Zhang L, Ying L, Meng F, Wu S, Wang P, Gao Y, He X, et al. Effectiveness of Norplant implants through seven years: a large-scale study in China. Contraception. 1995 Aug;52(2):99-103. doi: 10.1016/s0010-7824(95)00141-7.
citation: Sivin I, Lahteenmaki P, Mishell DR Jr, Alvarez F, Diaz S, Ranta S, Grozinger C, Lacarra M, Brache V, Pavez M, Nash H, Stern J. First week drug concentrations in women with levonorgestrel rod or Norplant capsule implants. Contraception. 1997 Nov;56(5):317-21. doi: 10.1016/s0010-7824(97)00153-4.
citation: Sivin I, Wan L, Ranta S, Alvarez F, Brache V, Mishell DR Jr, Darney P, Biswas A, Diaz S, Kiriwat O, Anant MP, Klaisle C, Pavez M, Schechter J. Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants. Contraception. 2001 Jul;64(1):43-9. doi: 10.1016/s0010-7824(01)00226-8.
citation: Smallwood GH, Meador ML, Lenihan JP, Shangold GA, Fisher AC, Creasy GW; ORTHO EVRA/EVRA 002 Study Group. Efficacy and safety of a transdermal contraceptive system. Obstet Gynecol. 2001 Nov;98(5 Pt 1):799-805. doi: 10.1016/s0029-7844(01)01534-4.
citation: Westhoff, C. Higher body weight does not affect NuvaRing's efficacy. Obstet Gynecol 2005; 104: 56S.
citation: Zieman M, Guillebaud J, Weisberg E, Shangold GA, Fisher AC, Creasy GW. Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data. Fertil Steril. 2002 Feb;77(2 Suppl 2):S13-8. doi: 10.1016/s0015-0282(01)03275-7.