Advances in contraceptive vaginal rings: what does the future hold?

References

• Sedgh G, Singh S, Hussain R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud Fam Plann. 2014;45(3):301–314.
   Web of Science ®Google Scholar
• Kavanaugh ML, Jerman J, Finer LB. Changes in use of long-acting reversible contraceptive methods among United States women, 2009–2012. Obstet Gynecol. 2015;126:917–927.
   PubMed Web of Science ®Google Scholar
• Alan Guttmacher Institute. Adding it up: investing in contraception and maternal and newborn health; 2017 [cited 2017 Jun]. Available from: https://www.guttmacher.org/fact-sheet/adding-it-up-contraception-mnh-2017.
   Google Scholar
• Hathaway M, Torres L, Vollett-Krech J, et al. Increasing LARC utilization: any woman, any place, any time. Clin Obstet Gynaecol. 2014 Dec;57(4):718–730.
   Web of Science ®Google Scholar
• Johansson ED, Sitruk-Ware R. New delivery systems in contraception: vaginal rings. Am J Obstet Gynecol. 2004;190(4 Suppl):S54–9.
   PubMed Web of Science ®Google Scholar
• Mishell DR, Lumkin ME. Contraceptive effect of varying dosages of progestogen in silastic vaginal rings. Fertil Steril. 1970;21:99–103.
   PubMed Web of Science ®Google Scholar
• Malcom R, Fetherston S, McCoy C, et al. Vaginal rings for delivery of HIV microbicides. Int J Women’s Health. 2012;4:595–605.
   PubMedGoogle Scholar
• Hoffman AS. The origins and evolution of “controlled” drug delivery systems. J Control Release. 2008 18;132(3): 153–163.
   PubMed Web of Science ®Google Scholar
• Gallegos AJ. Vaginal steroidal contraception. In: Zatuchni GI, Labbok MH, Sciarra JJ, editors. Research frontiers in fertility regulation. Hagerstown: Harper and Row; 1980. p. 230–246.
   Google Scholar
• Mishell DR, Moore DE, Roy S, et al. 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.
   PubMed Web of Science ®Google Scholar
• Toivonen J, Lahteenmaki P, Luukkainen T. Pituitary and gonadal function during the use of norgestrel–estradiol vaginal rings. Contraception. 1978;18:201–211.
   PubMed Web of Science ®Google Scholar
• Jackanicz TM. Levonorgestrel and estradiol release from an improved contraceptive vaginal ring. Contraception. 1981;24:323–339.
   PubMed Web of Science ®Google Scholar
• Sivin I, Mishell D Jr, Victor A, et al. A multicenter study of levonorgestrel–estradiol contraceptive vaginal rings. I: use effectiveness. An international comparative trial. Contraception. 1981;24:341–358.
   PubMed Web of Science ®Google Scholar
• Sivin I, Mishell D Jr, Victor A, et al. A multicenter study of levonorgestrel–estradiol contraceptive vaginal rings. II: subjective and objective measures of effects. An international comparative trial. Contraception. 1981;24(4):359–376.
   PubMed Web of Science ®Google Scholar
• Ahren T, Lithell H, Victor A, et al. 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(4):451–468.
   PubMed Web of Science ®Google Scholar
• Adams MR, Clarkson TB, Koritnik DR, et al. Contraceptive steroids and coronary artery atherosclerosis in cynomolgus macaques. Fertil Steril. 1987;47:1010–1018.
   PubMed Web of Science ®Google Scholar
• Victor A, Lithe H, Selinus I, et al. Pharmacodynamics of a contraceptive vaginal ring releasing norethindrone and estradiol: ovarian function, bleeding control and lipoprotein patterns. Contraception. 1984;89(2):179–188.
   Google Scholar
• Ballagh S, Mishell D, Jackanicz T, et al. Dose-finding study of a contraceptive ring releasing norethindrone acetate/ethinyl estradiol. Contraception. 1994;50(6):535–549.
   PubMed Web of Science ®Google Scholar
• Ballagh SA, Mishell DR Jr, Lacarra M, et al. A contraceptive vaginal ring releasing norethindrone acetate and ethinyl estradiol. Contraception. 1994;50(6):517–533.
   PubMed Web of Science ®Google Scholar
• Weisberg E, Fraser IS, Lacarra M, et al. Effect of different insertion regimens on side effects with a combination contraceptive vaginal ring. Contraception. 1997;56(4):233–239.
   PubMed Web of Science ®Google Scholar
• Weisberg E, Fraser IS, Mishell DR Jr, et al. A comparative study of two contraceptive vaginal rings releasing norethindrone acetate and doses of ethinylestradiol. Contraception. 1999;59(5):305–310.
   PubMed Web of Science ®Google Scholar
• Weisberg E, Fraser IS, Lacarra M, et al. Efficacy, bleeding patterns, and side effects of a 1-year contraceptive vaginal ring. Contraception. 1999;59(5):311–318.
   PubMed Web of Science ®Google Scholar
• Laurikka-Routti M, Haukkamaa M, Heikinheimo O. A contraceptive vaginal ring releasing EE and the progestin ST1435: bleeding control, serum steroid concentrations, serum lipids and serum chemistry. Contraception. 1990;42(1):111–120.
   PubMed Web of Science ®Google Scholar
• Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006;12(2):169–178.
   PubMed Web of Science ®Google Scholar
• Alvarez-Sanchez F, Brache V, Jackanicz T, et al. Evaluation of four different contraceptive vaginal rings: steroid serum levels, luteal activity, bleeding control and lipid profiles. Contraception. 1992;46(4):387–398.
   PubMed Web of Science ®Google Scholar
• Brache V, Mishell DR, Lahteenmaki P, et al. Ovarian function during use of vaginal rings delivering three different doses of NES. Contraception. 2001;63(5):257–261.
   PubMed Web of Science ®Google Scholar
• Laurikka-Routti M, Haukkamaa M, Heikinheimo O. A contraceptive vaginal ring releasing ethinyl estradiol and the progestin ST-1435: bleeding control, serum steroid concentrations, serum lipids and serum chemistry. Contraception. 1990 Jul;42(1):111–120.
   PubMed Web of Science ®Google Scholar
• Sivin I, Mishell DR, Alvarez F, et al. Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: a 1-year dose-finding trial. Contraception. 2005;71(2):122–129.
   PubMed Web of Science ®Google Scholar
• Weisberg E, Brache V, Alvarez F, et al. 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(1):46–52.
   PubMed Web of Science ®Google Scholar
• Fraser IS, Weisberg E, Brache V, et al. Serum Nestorone and ethinylestradiol levels, and ovulation inhibition in women using three different dosage combinations of a Nestorone® progestogen–ethinylestradiol contraceptive vaginal ring on a bleeding-signaled regimen. Contraception. 2005;72(1):40–45.
   PubMed Web of Science ®Google Scholar
• Apter D, Cacciatore B, Stenman UH, et al. Clinical performance and endocrine profiles of contraceptive vaginal rings releasing 3-keto-desogestrel and ethynilestradiol. Contraception. 1990;42(3):285–295.
   PubMed Web of Science ®Google Scholar
• Olsson SE, Odlind V. Contracepton with a vaginal ring releasing 3-keto-desogestrel and ethynilestradiol. Contraception. 1990;42(5):563–572.
   PubMed Web of Science ®Google Scholar
• Kirkman RJ, Bounds W, Colliver D, et al. Practical experience in the UK with an oestrogen/progestogen contraceptive vaginal ring. Br J Fam Plann. 1992;18:12–15.
   Google Scholar
• Brache V, Alvarez-Sanchez F, Faundes A, et al. Progestin-only contraceptive rings. Steroids. 2000;65(10–11):687–691.
   PubMed Web of Science ®Google Scholar
• Massai R, Diaz S, Jackanicz T, et al. Vaginal rings for contraception in lactating women. Steroids. 2000;65:703–707.
   PubMed Web of Science ®Google Scholar
• Koetsawang S, Ji G, Krishna U, et al. Microdose intravaginal levonorgestrel contraception: a multicenter clinical trial: I. Contractive efficacy and side effects. A World Health Organization task force on long-acting systemic agents for fertility regulation. Special programme of research development and research training in human reproduction. Contraception. 1990;41(2):105–124.
   PubMed Web of Science ®Google Scholar
• Diaz S, Jackanicz TM, Herreros C, et al. Fertility regulation in nursing women. VIII. Progesterone plasma levels and contraceptive efficacy of progesterone-releasing vaginal rings. Contraception. 1985;32(6):603–622.
   PubMed Web of Science ®Google Scholar
• Sivin I, Diaz S, Croxatto H, et al. Contraception for lactating women: a comparative trial of a progesterone-releasing vaginal ring and the cooper T 380 IUD. Contraception. 1997;55(4):225–232.
   PubMed Web of Science ®Google Scholar
• Roumen F, Apter D, Mulders T, et al. Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl estradiol. Hum Reprod. 2001;16(3):469–475..
   PubMed Web of Science ®Google Scholar
• Thurman AR, Clark MR, Hurlburt JA, et al. Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies. Int J Women’s Health. 2013;5:695–708.
   PubMedGoogle Scholar
• Algorta J, Diaz M, de Benito R, et al. Pharmacokinetic bioequivalence, safety and acceptability of Ornibel®, a new polymer composition contraceptive vaginal ring compared with Nuvaring. Eur J Contracept Reprod Health Care. 2017;22(6):429–438.
   PubMed Web of Science ®Google Scholar
• RamaRao S, Clark H, Merkatz R, et al. Progesterone vaginal ring: introducing a contraceptive to meet the needs of breastfeeding women. Contraception. 2013;88(5):591–598.
   PubMed Web of Science ®Google Scholar
• Brache V, Faundes A. Contraceptive vaginal rings: a review. Contraception. 2010;82:418–427.
   PubMed Web of Science ®Google Scholar
• Lobo RA, Stanczyk FZ. New knowledge in the physiology of hormonal contraceptives. Am J Obstet Gynecol. 1994;170(5 Pt 2):1499–1507.
   PubMed Web of Science ®Google Scholar
• Dieben TO, Roumen FJ, Apter D. Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol. 2002;100(3):585–593.
   PubMed Web of Science ®Google Scholar
• Dragoman M, Petrie K, Torgal A, et al. Contraceptive vaginal ring effectiveness is maintained during six weeks use: a prospective study of normal BMI and obese women. Contraception. 2013;87(4):432–436.
   PubMed Web of Science ®Google Scholar
• Sulak PJ, Smith V, Coffee A, et al. Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial. Obstet Gynecol. 2008;112(3):563–571.
   PubMed Web of Science ®Google Scholar
• López-Picado A, Lapuente O, Lete I. Efficacy and side-effects profile of the ethinylestradiol and etonogestrel contraceptive vaginal ring: a systematic review and meta-analysis. Eur J Contracept Reprod Health Care. 2017;22(2):131–146.
   PubMed Web of Science ®Google Scholar
• \Oddsson K, Leifels-Fischer B, Wiel-Masson D, et al. Superior cycle control with a contraceptive vaginal ring compared with an oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel: a randomized trial. Hum Reprod. 2005;20(2):557–562.
   PubMed Web of Science ®Google Scholar
• Timmer CJ, Mulders TM. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokinet. 2000;39(3):233–242.
   PubMed Web of Science ®Google Scholar
• Nguyen BT, Jensen JT. Evaluating the efficacy and safety of a progestin- and estrogen-releasing ethylene vinyl acetate copolymer contraceptive vaginal ring. Expert Opin Drug Saf. 2014;13(10):1423–1430.
   PubMed Web of Science ®Google Scholar
• Lidegaard O, Nielsen LH, Skovland CW. Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001–10. BMJ. 2012;344 10:e 2990.
   Web of Science ®Google Scholar
• Shapiro S, Dinger J. Risk of venous thromboembolism among users of oral contraceptives: a review of two recently published studies. J Fam Plann Reprod Health Care. 2010;36(1):33–38.
   PubMedGoogle Scholar
• Dinger J, Mohner S, Klass H. Cardiovascular risk associated with the use of an etonogestrel-containing vaginal ring. Obstet Gynecol. 2013;122(4):800–808.
   PubMed Web of Science ®Google Scholar
• Miller L, Verhoeven CH, Hout J. Extended regimens of the contraceptive vaginal ring: a randomized trial. Obstet Gynecol. 2005;106(3):473–482.
   PubMed Web of Science ®Google Scholar
• Guazzelli CA, Barreiros FA, Barbosa R, de Araújo FF, Moron AF. Extended regimens of the vaginal contraceptive ring: cycle control. Contraception. 2009;80(5):430–435.
   Google Scholar
• Barreiros FA, Guazzelli CA, de Araújo FF, et al. Bleeding patterns of women using extended regimens of the contraceptive vaginal ring. Contraception. 2007;75(3):204–208.
   Google Scholar
• Edelman A, Micks E, Gallo MF, et al. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev. 2014;29(7):CD004695.
   PubMed Web of Science ®Google Scholar
• Benson LS, Micks EA. Why stop now? Extended and continuous regimens of combined hormonal contraceptive methods. Obstet Gynecol Clin North Am. 2015;42(4):669–681.
   PubMed Web of Science ®Google Scholar
• Barreiros FA, Guazzelli CA, Barbosa R, et al. Extended regimens of the combined contraceptive vaginal ring containing etonogestrel and ethinyl estradiol: effects on lipid metabolism. Contraception. 2011;84(2):155–159.
   PubMed Web of Science ®Google Scholar
• Stifani BM, Plagianos M, Vieira CV, et al. Factors associated with nonadherence to instruction for use the Nestorone®/ehtynil estradiol contraceptive vaginal ring. Contraception. 2018;97:415–421.
   PubMed Web of Science ®Google Scholar
• Merkatz RB, Plagianos M, Hoskin E, et al. Acceptability of the Nestorone®/ehtynil estradiol contraceptive vaginal ring: development of a model; implication for introduction. Contraception. 2014 November;90(5):514–521.
   PubMed Web of Science ®Google Scholar
• WHO. Colaborative study of cardiovascular disease and steroid hormone contraception. Venous thromboembolic disease and combined oral contraceptives:results of international multicenter case-control study. Lancet. 1995;346:1575–1582.
   PubMed Web of Science ®Google Scholar
• Brache V, Payan L, Faundes A. Current status of contraceptive vaginal rings. Contraception. 2013;87(3):264–272.
   PubMed Web of Science ®Google Scholar
• Larner JM, Reel JR, Blye RP. Circulating concentrations of antiprogestins CDB-2914 and mifepristone in female rhesus monkey following various routes of administration. Hum Reprod. 2000;15(5):1100–1106.
   PubMed Web of Science ®Google Scholar
• Brache V, Sitruk-Ware R, Williams A, et al. 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(5):480–488.
   PubMed Web of Science ®Google Scholar
• Schurmans C, De Baetselier I, Kestelyn E, et al. The ring plus project: safety and acceptability of vaginal rings that protect women from unintended pregnancy. BMC Public Health. 2015;10(15):348.
   Web of Science ®Google Scholar
• Devlin B, Nuttall J, Wilder S, et al. Development of dapivirine vaginal ring for HIV prevention. Antiviral Res. 2013;100(Suppl):S3–S8.
   PubMed Web of Science ®Google Scholar
• Rohan LC, Devlin B, Yang H. Microbicide dosage forms. Curr Top Microbiol Immunol. 2014;383:27–54.
   PubMed Web of Science ®Google Scholar
• Saxena BB, Han YA, Fu D, et al. Sustained release of microbicides by newly engineered vaginal rings. Aids. 2009;23(8):917–922.
   PubMed Web of Science ®Google Scholar
• Woolfson AD, Elliott GR, Gilligan CA, et al. Design of an intravaginal ring for the controlled delivery of 17 beta-estradiol as its 3-acetate ester. J Control Release. 1999;61(3):319–328.
   PubMed Web of Science ®Google Scholar
• Kumar N, Koide SS, Tsong Y, et al. Nestorone a progestin with a unique pharmacological profile. Steroids. 2000;65(10–11):629–636.
   PubMed Web of Science ®Google Scholar