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

Pharmacokinetics Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00710606
• Other study ID #: AAAC8127
• Status: Completed
• Phase: N/A
• First received: July 1, 2008
• Last updated: April 14, 2015
• Start date: June 2008
• Est. completion date: December 2008

Study information

• Verified date: April 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

Drug:
• NuvaRing
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.
• NuvaRing
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.

Locations

Country	Name	City	State
United States	Division of Family Planning and Preventive Services	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	Organon

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

Sivin I, Lähteenmäki 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. — View 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. — View 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. — View Citation

Westhoff, C. Higher body weight does not affect NuvaRing's efficacy. Obstet Gynecol 2005; 104: 56S.

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No