Pharmacokinetics and Ovarian Suppression During Use of a Contraceptive Vaginal Ring in Normal-weight and Obese Women

Overview

Journal Am J Obstet Gynecol

Publisher Elsevier

Specialty Gynecology & Obstetrics

Date 2012 Jun 26

PMID 22727346

Citations 13

Authors

Carolyn L Westhoff

Anupama H Torgal

Elizabeth Rose Mayeda

Kelsey Petrie

Tiffany Thomas

Monica Dragoman

Serge Cremers

Affiliations

Soon will be listed here.

Abstract

Objective: Many observational studies indicate higher oral contraceptive failure among obese women, but most clinical trials and physiologic studies do not support these differences. Limited data indicate higher failure rates among obese contraceptive patch users. Data regarding contraceptive vaginal ring performance in obese women are needed.

Study Design: Twenty normal weight (body mass index [BMI] 19.0-24.9; median, 21.65) and 20 obese (BMI 30.0-39.9; median, 33.7) women enrolled in a prospective study of ethinyl estradiol (EE(2)) and etonorgestrel pharmacokinetics and of ovarian follicle development, endometrial thickness, and bleeding patterns, all measured biweekly during the second cycle of contraceptive vaginal ring use.

Results: Thirty-seven women completed follow-up. Mean day 0-21 EE(2) concentrations were lower among obese vs normal weight women (15.0 vs 22.0 pg/mL, respectively, P = .004), whereas etonorgestrel concentrations were similar (1138 vs 1256 pg/mL, respectively, P = .39). Follicular development was minimal in both groups, with only 5 women achieving a maximum follicle diameter >13 mm at any time during 3 weeks follow-up (3 normal weight and 2 obese women); these women had serum progesterone levels <1.0. Obese women reported more bleeding or spotting than normal weight women (3.6 vs 1.4 days, respectively, P = .01).

Conclusion: Although obese women had lower EE(2) levels during contraceptive vaginal ring use, they had excellent suppression of ovarian follicle development, similar to normal weight women. This predicts that contraceptive vaginal ring effectiveness will be similar in women with a BMI up to 39.9. The lower serum EE(2) levels in the obese women may explain the greater reported bleeding or spotting days.

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Contraceptive Options Following Gestational Diabetes: Current Perspectives.

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References

Belsey E, Machin D, DArcangues C . The analysis of vaginal bleeding patterns induced by fertility regulating methods. World Health Organization Special Programme of Research, Development and Research Training in Human Reproduction. Contraception. 1986; 34(3):253-60. DOI: 10.1016/0010-7824(86)90006-5. View

Timmer C, Mulders T . Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokinet. 2000; 39(3):233-42. DOI: 10.2165/00003088-200039030-00005. View

Westhoff C, Torgal A, Mayeda E, Pike M, Stanczyk F . Pharmacokinetics of a combined oral contraceptive in obese and normal-weight women. Contraception. 2010; 81(6):474-80. PMC: 3522459. DOI: 10.1016/j.contraception.2010.01.016. View

Broome M, Clayton J, FOTHERBY K . Enlarged follicles in women using oral contraceptives. Contraception. 1995; 52(1):13-6. DOI: 10.1016/0010-7824(95)00127-v. View

Grimes D, Godwin A, Rubin A, Smith J, Lacarra M . Ovulation and follicular development associated with three low-dose oral contraceptives: a randomized controlled trial. Obstet Gynecol. 1994; 83(1):29-34. View

Rible R, Taylor D, Wilson M, Stanczyk F, Mishell Jr D . Follicular development in a 7-day versus 4-day hormone-free interval with an oral contraceptive containing 20 mcg ethinyl estradiol and 1 mg norethindrone acetate. Contraception. 2009; 79(3):182-8. DOI: 10.1016/j.contraception.2008.10.005. View

Mulders T, Dieben T . Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition. Fertil Steril. 2001; 75(5):865-70. DOI: 10.1016/s0015-0282(01)01689-2. View

Dinger J, Minh T, Buttmann N, Bardenheuer K . Effectiveness of oral contraceptive pills in a large U.S. cohort comparing progestogen and regimen. Obstet Gynecol. 2011; 117(1):33-40. DOI: 10.1097/AOG.0b013e31820095a2. View

Holt V, Cushing-Haugen K, Daling J . Body weight and risk of oral contraceptive failure. Obstet Gynecol. 2002; 99(5 Pt 1):820-7. DOI: 10.1016/s0029-7844(02)01939-7. View

10.

Spona J, Binder N, Hoschen K, Feichtinger W . Suppression of ovarian function by a combined oral contraceptive containing 0.02 mg ethinyl estradiol and 2 mg chlormadinone acetate given in a 24/4-day intake regimen over three cycles. Fertil Steril. 2009; 94(4):1195-1201. DOI: 10.1016/j.fertnstert.2009.06.057. View

11.

Dinger J, Cronin M, Mohner S, Schellschmidt I, Minh T, Westhoff C . Oral contraceptive effectiveness according to body mass index, weight, age, and other factors. Am J Obstet Gynecol. 2009; 201(3):263.e1-9. DOI: 10.1016/j.ajog.2009.03.017. View

12.

Hoogland H, Skouby S . Ultrasound evaluation of ovarian activity under oral contraceptives. Contraception. 1993; 47(6):583-90. DOI: 10.1016/0010-7824(93)90025-3. View

13.

Schlaff W, Lynch A, Hughes H, Cedars M, Smith D . Manipulation of the pill-free interval in oral contraceptive pill users: the effect on follicular suppression. Am J Obstet Gynecol. 2004; 190(4):943-51. DOI: 10.1016/j.ajog.2004.02.012. View

14.

Blouin K, Veilleux A, Luu-The V, Tchernof A . Androgen metabolism in adipose tissue: recent advances. Mol Cell Endocrinol. 2008; 301(1-2):97-103. DOI: 10.1016/j.mce.2008.10.035. View

15.

Kuhnz W, Pfeffer M . Protein binding of the contraceptive steroids gestodene, 3-keto-desogestrel and ethinylestradiol in human serum. J Steroid Biochem. 1990; 35(2):313-8. DOI: 10.1016/0022-4731(90)90290-9. View

16.

Cushman M, Callas P, Denenberg J, Bovill E, Criqui M . Risk factors for peripheral venous disease resemble those for venous thrombosis: the San Diego Population Study. J Thromb Haemost. 2010; 8(8):1730-5. PMC: 2937057. DOI: 10.1111/j.1538-7836.2010.03924.x. View

17.

Holt V, Scholes D, Wicklund K, Cushing-Haugen K, Daling J . Body mass index, weight, and oral contraceptive failure risk. Obstet Gynecol. 2004; 105(1):46-52. DOI: 10.1097/01.AOG.0000149155.11912.52. View

18.

Westhoff C, Hait H, Reape K . Body weight does not impact pregnancy rates during use of a low-dose extended-regimen 91-day oral contraceptive. Contraception. 2011; 85(3):235-9. DOI: 10.1016/j.contraception.2011.08.001. View

19.

Hammond G, Langley M, Robinson P, Nummi S, Lund L . Serum steroid binding protein concentrations, distribution of progestogens, and bioavailability of testosterone during treatment with contraceptives containing desogestrel or levonorgestrel. Fertil Steril. 1984; 42(1):44-51. DOI: 10.1016/s0015-0282(16)47956-2. View

20.

Westhoff C, Torgal A, Mayeda E, Stanczyk F, Lerner J, Benn E . Ovarian suppression in normal-weight and obese women during oral contraceptive use: a randomized controlled trial. Obstet Gynecol. 2010; 116(2 Pt 1):275-283. DOI: 10.1097/AOG.0b013e3181e79440. View