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

• Sponsor: Columbia University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00710606
• Collaborator: Organon (Industry)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 6
• Patients Per Site Per Month: 6.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics	Drug: NuvaRing; Drug: NuvaRing	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Official Title: Comparison of Serum Contraceptive Hormone Levels Between Normal Weight and Obese Users of the NuvaRing®
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1- Obese Women /Nuvaring 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; 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.
Active Comparator: 2- Normal Weight / Nuvaring 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; 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.

Outcome Measures

Primary Outcome Measures

1. Mean Serum Concentrations of Etonogestrel and Ethinyl Estradiol [Measurements at Week 3 and Week 6 continuous ring use]

   Serum concentrations were obtained from thirty-seven women completed follow-up.

Secondary Outcome Measures

1. Number of Participants Achieving a Maximum Follicle Diameter > 13mm During the 3 Weeks of Follow-up [continuous ring use, an average of 3 weeks]

   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).

2. Mean Endometrial Proliferation [Transvaginal ultrasound measurements of endometrial proliferation will be completed over continuous ring use, an average of 3 weeks]

   The mean endometrial proliferation from week 1, week 2 and week3

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Division of Family Planning and Preventive Services	New York	New York	United States	10032

Sponsors and Collaborators

• Columbia University
• Organon

Investigators

• Principal Investigator: Carolyn Westhoff, MD, MSc, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Carolyn L. Westhoff, Director of Family Planning and Preventive Services Division, Columbia University
• ClinicalTrials.gov Identifier: NCT00710606
• Other Study ID Numbers: AAAC8127
• First Posted: Jul 4, 2008
• Last Update Posted: Apr 30, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by Carolyn L. Westhoff, Director of Family Planning and Preventive Services Division, Columbia University: contraceptive ring; obesity; pharmacokinetics; pharmacodynamics; Pharmacokinetics of the contraceptive ring in obese women.
• Additional relevant MeSH terms: NuvaRing; Ethinyl Estradiol; Desogestrel

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled during the months of June-September 2008.

Arm/Group Title	Obese Subjects	Normal Weight Subjects
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	20	20
COMPLETED	20	18
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Obese Subjects	Normal Weight Subjects	Total
Arm/Group Description	Obese subjects (BMI 30-39.9)	Normal weight subjects (BMI 19-24.9)	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.5 (3.2)	26.0 (3.6)	25.8 (3.7)
Sex: Female, Male (Count of Participants)
Female	20 100%	20 100%	40 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

17 participants in each group was planned a priori to have 80% power to identify a one standard deviation difference in the mean serum levels of the contraceptive hormones. We enrolled 40 women, 2 withdrew prior to the study cycle. We excluded one woman due to removal of the CVR during the study cycle leaving 18 normal weight and 19 obese women.

Arm/Group Title	Normal Weight	Obese
Arm/Group Description	Women of normal weight and obese received two contraceptive rings. During the second cycle of ring use, subject returned to the study site for serial serum hormone measurements and transvaginal ultrasound twice weekly during four weeks of continuous use.	Women of normal weight and obese received two contraceptive rings. During the second cycle of ring use, subject returned to the study site for serial serum hormone measurements and transvaginal ultrasound twice weekly during four weeks of continuous use.
Measure Participants	18	19
Etonogesterel (ENG) Week 3	1275	1240
Ethinyl Estradiol (EE) Week 3	21.9	14.8
Etonogesterel (ENG) Week 6	1063	1096
Ethinyl Estradiol (EE) Week 6	16.2	12.5

2. Secondary Outcome

Title	Number of Participants Achieving a Maximum Follicle Diameter > 13mm During the 3 Weeks of Follow-up
Description	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).
Time Frame	continuous ring use, an average of 3 weeks

Outcome Measure Data

Analysis Population Description

17 participants in each group was planned a priori to have 80% power to identify a one standard deviation difference in the mean serum levels of the contraceptive hormones. We enrolled 40 women, 2 withdrew prior to the study cycle. We excluded one woman due to removal of the CVR during the study cycle leaving 18 normal weight and 19 obese women.

Arm/Group Title	Obese Subjects	Normal Weight Subjects
Arm/Group Description	Obese subjects (BMI 30-39.9)	Normal weight subjects (BMI 19-24.9)
Measure Participants	19	18
Number [Participant w/follicular diameter >=13mm]	2	3

3. Secondary Outcome

Title	Mean Endometrial Proliferation
Description	The mean endometrial proliferation from week 1, week 2 and week3
Time Frame	Transvaginal ultrasound measurements of endometrial proliferation will be completed over continuous ring use, an average of 3 weeks

Outcome Measure Data

Analysis Population Description

17 participants in each group was planned a priori to have 80% power to identify a one standard deviation difference in the mean serum levels of the contraceptive hormones. We enrolled 40 women, 2 withdrew prior to the study cycle. We excluded one woman due to removal of the CVR during the study cycle leaving 18 normal weight and 19 obese women.

Arm/Group Title	Obese Subjects	Normal Weight Subjects
Arm/Group Description	Obese subjects (BMI 30-39.9)	Normal weight subjects (BMI 19-24.9)
Measure Participants	19	18
Mean (Standard Deviation) [millimeters]	4.7 (1.8)	3.9 (1.6)

Adverse Events

Time Frame	3 months
Arm/Group Title	Obese Subjects		Normal Weight Subjects
Arm/Group Description	Obese subjects (BMI 30-39.9)		Normal weight subjects (BMI 19-24.9)
All Cause Mortality
	Obese Subjects		Normal Weight Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Obese Subjects		Normal Weight Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		2/20 (10%)
Musculoskeletal and connective tissue disorders
fractured pelvis	0/20 (0%)	0	1/20 (5%)	1
Vascular disorders
venous thrombosis	0/20 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Obese Subjects		Normal Weight Subjects
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.