Abstract
Contraceptive vaginal rings (CVR) offer a new, effective contraceptive option, expanding
the available choices of hormonal contraception. Various ring prototypes have been
evaluated: progestin-only rings and combined progestin-estrogen rings, as well as
different combination of progestins and estrogens. The progestin-only ring is intended
for continuous use, whereas the combined ring has been designed for cyclic 3-week
in/1-week out use, although several studies have explored alternative schemes of extended
use. However, only two ring designs have reached the market: NuvaRing, a 1-month combined
ring that releases etonogestrel and ethinylestradiol, and Progering, a 3-month progesterone-releasing
ring for use in lactating women. A one year Nestorone/ethinyl estradiol CVR is approaching
the final stages of development, as the Population Council is preparing to submit
a new drug application to the Food and Drug Administration. The main advantages of
CVRs are their effectiveness (similar or slightly better than the pill), ease of use
without the need of remembering a daily routine, user ability to control initiation
and discontinuation, nearly constant release rate allowing for lower doses, greater
bioavailability and good cycle control with the combined ring, in comparison with
oral contraceptives. Current prototypes in development include rings releasing progesterone
receptor modulators, which would provide estrogen-free contraception, as well as combined
rings releasing estradiol, instead of ethinyl-estradiol, providing a safer profile.
Furthermore, intensive efforts towards developing dual protection rings, providing
both contraception and protection against reproductive tract infections, offer hope
that this greatly needed technology will soon undergo clinical testing and will be
in the hands of women worldwide in the near future.
Keywords
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References
- Contraceptive technologies: responding to women's needs. Guttmacher Institute, New York2011
- Strategies to prevent unintended pregnancy: increasing use of long-acting reversible contraception.Hum Reprod Update. 2011; 17: 121-137
- Unintended pregnancy in sub-Saharan Africa: magnitude of the problem and potential role of contraceptive implants to alleviate it.Contraception. 2008; 78: 73-78
- Contraceptive effect of varying dosages of progestogen in Silastic vaginal rings.Fertil Steril. 1970; 21: 99-103
- Passage of steroids through silicone rubber.Endocrinology. 1966; 78: 208
- The physiologic effectiveness of progesterone vaginal suppositories.J Clin Endocrinol Metab. 1954; 14: 1564-1567
- The absorption of conjugated estrogens and sodium estrone sulfate from the vagina.Ann Chir Gynecol Fenn. 1974; 63: 186-190
- Why consider vaginal drug administration?.Fertil Steril. 2004; 82: 1-12
- Progestin-only contraceptive rings.Steroids. 2000; 65: 687-696
- Pharmacokinetics and pharmacodynamic investigation with vaginal devices releasing levonorgestrel at a constant near zero order rate.Contraception. 1982; 26: 567-585
- The in vivo release characteristics of a multi-compartment vaginal ring releasing 3-keto-desogetrel.Contraception. 1989; 40: 615-621
- Pharmacokinetics of etonorgestrel and ethynil estradiol released from a combined contraceptive vaginal ring.Clin Pharmacokinet. 2000; 39: 233-242
- Fertility regulation in nursing women: VIII. Progesterone plasma levels and contraceptive efficacy of progesterone-releasing vaginal rings.Contraception. 1985; 32: 603-622
- Fertility regulation in nursing women. IX. Contraceptive performance, duration of lactation, infant growth, and bleeding patterns during use of progesterone vaginal rings, progestin-only pills, Norplant implants, and Copper T 380A intrauterine devices.Contraception. 1997; 56: 223-232
- Progesterone vaginal ring for contraceptive use during lactation.Contraception. 2010; 82: 428-434
- Preregistration study on the safety and contraceptive efficacy of the progesterone-releasing vaginal ring in Chilean nursing women.Contraception. 1999; 60: 9-14
- Contraception for lactating women: a comparative trial of a progesterone-releasing vaginal ring and the copper T 380 IUD.Contraception. 1997; 55: 225-232
- Extended use of a progesterone-releasing vaginal ring in nursing women: a Phase II clinical trial.Contraception. 2005; 72: 352-357
- Task Force on Long-Acting Systemic Agents for Fertility Regulation Special Programme of Research, Development and Research Training in Human Reproduction. Microdose intravaginal levonorgestrel contraception: a multicenter clinical trial. I. Contraceptive efficacy and side effects.Contraception. 1990; 41: 105-124
- Preliminary report of unexpected local reactions to a progestogen-releasing contraceptive vaginal ring.Eur J Obstet Gynecol Reprod Biol. 1993; 48: 123-125
- Ovarian function during use of vaginal rings delivering three different doses of NES.Contraception. 2001; 63: 257-261
- Vaginal rings for contraception in lactating women.Steroids. 2000; 65: 703-707
- Clinical performance and endocrine profile with contraceptive vaginal rings containing a combination of estradiol and d-norgestrel.Am J Obstet Gynecol. 1978; 130: 55-62
- Pituitary and gonadal function during the use of norgestrel-estradiol vaginal rings.Contraception. 1978; 18: 201-211
- A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. I. Use-effectiveness. An international comparative trial.Contraception. 1981; 24: 341-358
- A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. II. Subjective and objective measures of effects. An international comparative trial.Contraception. 1981; 24: 359-376
- A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. III. Menstrual patterns. An international comparative trial.Contraception. 1981; 24: 377-392
- Comparison of the metabolic effects of two hormonal contraceptive methods: An oral formulation and a vaginal ring II. Serum lipoproteins and apolipoproteins.Contraception. 1981; 24: 471-478
- Lipoprotein patterns in women in Santo Domingo using a levonorgestrel/estradiol contraceptive ring.Contraception. 1981; 24: 469-480
- The effect on lipids and lipoproteins of a contraceptive vaginal ring containing levonorgestrel and estradiol.Contraception. 1981; 24: 429-449
- Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques.Fertil Steril. 1987; 47: 1010-1018
- Dose-finding study of a contraceptive ring releasing norethindrone acetate/ethinyl estradiol.Contraception. 1994; 50: 535-549
- A contraceptive vaginal ring releasing norethindrone acetate and ethinyl estradiol.Contraception. 1994; 50: 517-533
- A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and differing doses of ethinyl estradiol.Contraception. 1999; 59: 305-310
- Efficacy, bleeding patterns, and side effects of a 1-year contraceptive vaginal ring.Contraception. 1999; 59: 311-318
- Evaluation of four different contraceptive vaginal rings: steroid serum levels, luteal activity, bleeding control and lipid profiles.Contraception. 1992; 46: 387-398
- A contraceptive vaginal ring releasing EE and the progestin ST1435: Bleeding control, serum steroid concentrations, serum lipids and serum chemistry.Contraception. 1990; 42: 111-120
- Contraceptive vaginal rings releasing Nestorone and ethinylestradiol : a 1-year dose-finding trial.Contraception. 2005; 71: 122-129
- Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone progestogen-ethinyl estradiol contraceptive vaginal ring on a bleeding-signaled regimen.Contraception. 2005; 72: 40-45
- Clinical performance and menstrual bleeding patterns with three dosage combinations of a Nestorone® progestogen/ethinyl estradiol contraceptive vaginal ring used on a bleeding-signaled regimen.Contraception. 2005; 72: 46-52
- Vaginal epithelial surface appearances in women using vaginal rings for contraception.Contraception. 2000; 61: 131-138
- Feasibility study of Nestorone®—ethinylestradiol vaginal contraceptive ring for emergency contraception.Contraception. 2006; 73: 46-52
- Clinical performance and endocrine profiles of contraceptive vaginal rings releasing 3-keto-desogestrel and ethinylestradiol.Contraception. 1990; 42: 285-295
- Contraception with a vaginal ring releasing 3-keto-desogestrel and ethinylestradiol.Contraception. 1990; 42: 563-572
- Pharmacokinetics of 3-keto-desogestrel and ethinylestradiol released from different types of contraceptive vaginal rings.Contraception. 1990; 42: 629-642
- Practical experience in the UK with an oestrogen/progestogen contraceptive vaginal ring.Br J Fam Planning. 1992; 18: 12-15
- Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive.Contraception. 2005; 72: 168-174
- Use of the novel combined vaginal ring NuvaRing for ovulation inhibition.Fertil Steril. 2001; 75: 865-870
- Ovarian function with the contraceptive vaginal ring or an oral contraceptive: randomized study.Hum Reprod. 2004; 19: 2668-2673
- Matched-pairs analysis of ovarian suppression during oral vs. vaginal hormonal contraceptive use.Contraception. 2011; 84: e1-e4
- Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl estradiol.Hum Reprod. 2001; 16: 469-475
- Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring.Obstet Gynecol. 2002; 100: 585-593
- Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial.Contraception. 2005; 71: 176-182
- Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 mcg of ethinyl estradiol and 3 mg of drospirenone.Contraception. 2006; 74: 451-457
- JME. The contraceptive vaginal ring compared with the combined oral contraceptive pill: a comprehensive review of randomized controlled trials.Contraception. 2007; 75: 420-429
- JME. Review of the combined contraceptive vaginal ring, (NuvaRing®). Therapeu Clin.Risk Manage. 2008; 4: 441-451
Lopez LM, Grimes DA, Gallo MF, Schulz KF. Skin patch and vaginal ring versus combined oral contraceptives for contraception. Cochrane Database of Systematic Reviews 2010, Issue 3. Art. No. CD003552. http://dx.doi.org/10.1002/14651858.CD003552.pub3.
- Wiel-Masson, Melo NR, Benedetto C, Verhoeven CHJ. Superior cycle control with contraceptive vaginal ring compared with an oral contraception containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel: a randomization trial.Hum Reprod. 2005; 20: 557-562
- Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol.Am J Obstet Gynecol. 2002; 186: 389-395
- Effects on cycle control and bodyweight of the combined contraceptive ring, NuvaRing, versus an oral contraceptive containing 30 mcg ethinyl estradiol and 3 mg drospirenone.Hum Reprod. 2006; 21: 2304-2311
- Bleeding patterns after immediate initiation of an oral compared with a vaginal hormonal contraceptive.Obstet Gynecol. 2005; 106: 89-96
- Extended regimens of the contraceptive vaginal ring: a randomized trial.Obstet Gynecol. 2005; 106: 473-482
- Bleeding patterns of women using extended regimens of the contraceptive vaginal ring.Contraception. 2007; 75: 204-208
- Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring. A randomized controlled trial.Obstet Gynecol. 2008; 112: 563-571
- Extended regimens of the vaginal contraceptive ring: cycle control.Contraception. 2009; 80: 430-435
- A comparison between the vaginal ring and oral contraceptives.Obstet Gynecol. 2004; 104: 555-563
- The combined contraceptive vaginal ring, NuvaRing®: an international study of user acceptability.Contraception. 2003; 67: 187-194
- A comparative study on the effects of a contraceptive vaginal ring NuvaRing and an oral contraceptive on carbohydrate metabolism and adrenal thyroid function.Eur J Contracep Reprod Health Care. 2004; 9: 131-140
- Effects of extended regimens of the contraceptive vaginal ring on carbohydrate metabolism.Contraception. 2012; 85: 253-256
- Contraceptive vaginal ring use for women has less adverse metabolic effects than an oral contraceptive.Contraception. 2007; 76: 348-356
- The combined contraceptive vaginal ring and bone mineral density in healthy pre-menopausal women.Hum Reprod. 2005; 20: 2764-2768
- Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study.Contraception. 2010; 81: 209-214
- The combined contraceptive vaginal ring (NuvaRing®) and endometrial histology.Contraception. 2005; 72: 362-365
- Medical eligibility criteria for new contraceptive methods: combined hormonal patch, combined hormonal vaginal ring and the etonogestrel implant.Contraception. 2006; 73: 134-144
Medical eligibility criteria for contraceptive use, 4th edition. Geneva: World Health Organization. 2010.
- Acceptability of the contraceptive vaginal ring by rural and urban population in two Latin American countries.Contraception. 1981; 24: 393-414
- User's perception of the contraceptive vaginal ring: a field study in Brazil and the Dominican Republic.Stud Fam Plann. 1983; 14: 284-290
- The acceptability of a combined estrogen/progestogen contraceptive vaginal ring.Contraception. 1995; 51: 39-44
- Clinical acceptability of an ethylene-vinyl-acetate non-medicated vaginal ring.Contraception. 1999; 59: 59-62
- The contraceptive vaginal ring: female adolescents’ knowledge, attitudes and plans for use.Contraception. 2007; 76: 444-450
- Acceptability of the vaginal contraceptive ring among adolescent women.J Pediatr Adolesc Gynecol. 2011; 24: 204-210
- Adolescent and young women's experience with the vaginal ring and oral contraceptive pills.J Pediatr Adolesc Gynecol. 2007; 20: 345-351
- Acceptability and satisfaction using Quick Start with the contraceptive vaginal ring versus oral contraceptive.Contraception. 2006; 73: 488-492
- Borgatta L, et al. Multicenter comparison of the contraceptive ring and patch: a randomized controlled trial.Obstet Gynecol. 2008; 111: 267-277
- The CHOICE study: effect of counseling on the selection of combined hormonal contraceptive methods in 11 countries.Eur J Contracept Reprod Health Care. 2012; 17: 65-78
- Differential lipemic and proteinemic response to oral ethynil estradiol and parenteral estradiol cypionate.Metabolism. 1980; 29: 803-805
- Comparison of hepatic impact of oral and vaginal administration of ethynil estradiol.Am J Obstet Gynecol. 1985; 151: 868-877
- Endocrine and clinical effects of micronized estradiol administered vaginally or orally.Fertil Steril. 2001; 75: 200-202
- Effects of oral and transvaginal ethinyl estradiol on hemostatic factors and hepatic proteins in a randomized, crossover study.J Clin Endocrinol Metab. 2007; 92: 2074-2079
- The contraceptive vaginal ring (NuvaRing) and hemostasis: a comparative study.Contraception. 2004; 69: 461-467
- Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral contraceptive containing levonorgestrel on hemostasis variables.Am J Obstet Gynecol. 2006; 195: 72-77
- Comparison of the impact of vaginal and oral administration of combined hormonal contraceptives on hepatic proteins sensitive to estrogen.Contraception. 2007; 75: 430-437
- Effects of the contraceptive patch, the vaginal ring and an oral contraceptive on APC resistance and SHBG: a cross over study.Thromb Res. 2009; 123: 429-435
- Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study.Lancet. 1995; 346: 1575-1582
- Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.Thromb Haemost. 2003; 89: 493-498
- Risk of venous thrombosis: obesity and its joint effect with oral contraceptive use and prothrombotic mutations.Br J Haematol. 2007; 139: 289-296
- Effects of a novel estrogen-free, progesterone receptor modulator contraceptive vaginal ring on inhibition of ovulation, bleeding patterns and endometrium in normal women.Contraception. 2012; 85: 480-488
- Delivery of microbicides to the vagina: difficulties reported with the use of three devices, adherence to use and preferences.Contraception. 2007; 76: 126-131
- Multipurpose prevention technologies: biomedical tools to prevent HIV-1, HSV-2, and unintended pregnancies.Infect Dis Obstet Gynecol. 2011; : 1-10
Microbicide Product Research and Development. Population Council Fact Sheet, April 2012.
Article Info
Publication History
Published online: October 08, 2012
Accepted:
August 26,
2012
Received:
July 12,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
