Review articleContraceptive vaginal rings: a review
Introduction
The availability of modern contraceptive methods has played a fundamental role in empowering women by reducing the burden of excessive childbearing and boosting women's opportunities for nondomestic activities. The increased availability of modern contraceptives has reduced maternal mortality and child mortality, and has made a very significant contribution to dramatically reducing the induced abortion rate in countries that had traditionally used abortion as a means of birth control [1].
Among the modern methods for fertility regulation, hormonal contraceptives have played a leading role. The combined oral pill was the first, and still the most, popular form of hormonal contraception. Although highly effective in controlled clinical studies, its effectiveness becomes considerably lower in real life, mostly for inadequate use, forgetting one or more pills or late initiation of a new cycle. This limitation led to the search for “long-acting” hormonal methods of contraception that do not require daily action by women.
Alternative nonoral routes for contraceptive steroids are available in the form of injections, subdermal implants, transdermal patches, gels or creams, intrauterine devices and by means of a plastic ring-shaped device placed in the vagina. The clinical application of the release of contraceptive steroids through the vagina was first demonstrated four decades ago, when Mishell and Lumkin [2] published their clinical study with a vaginal ring releasing medroxyprogesterone acetate.
The development of contraceptive vaginal rings (CVRs) with the optimal characteristics of size, an adequate release rate of progestin and estrogen compatible with contraceptive effectiveness and minimal side effects has been a long process. Numerous clinical trials, testing various doses and different steroids, have been published.
However, only two contraceptive rings have progressed to the stage of a marketed product: the NuvaRing (NV Organon, Oss, the Netherlands), which releases etonogestrel (ENG; 3-keto-desogestrel) and ethinylestradiol (EE), and Progering (Laboratorios Silesia, Santiago, Chile), the progesterone-releasing vaginal ring for nursing women.
Section snippets
Vaginal route of delivery
The concept of CVRs is based on a combination of two principles: the capacity of steroids to slowly diffuse at a constant rate through biocompatible silicone elastomers [3], and the capability of the vaginal epithelium to rapidly absorb steroids placed in the vagina into the circulation [4], [5]. The vascular supply of the vagina consists of a complex network of arteries and veins which favors the absorption of steroids and other molecules through the vaginal epithelium into the systemic
History of development
A considerable number of contraceptive rings delivering both a progestin and an estrogen, for cyclic use (3 weeks in/1 week out), as well as progestin-only rings for continuous use have been studied in the last four decades.
Effect of the vaginal route of delivery on hemostasis variables and liver proteins
It has been postulated that the administration of estrogens through the vaginal route would permit avoiding the approximately 60% first pass of the steroid through the liver that occurs after oral administration [52]. The hypothesis was that the same dose of estrogen administered vaginally would have the desired effect on the central nervous system without affecting hepatic metabolism as occurs after oral administration. Unfortunately, studies comparing the hepatic effect of the same estrogen
Progesterone ring for nursing women
Progesterone has potential advantages for contraception during lactation because it is the natural hormone and is nearly inactive when given by the oral route, thus is unlikely to affect the infant even when present in breast milk. This ring has a homogenous design with 22.5% w/w progesterone dispersed in silicone. The external diameter and its cross-sectional diameter are 58 and 8.4 mm, respectively. The in vitro release is approximately 10 mg/day of progesterone for an effective life span of
Conclusions
Contraceptive vaginal rings have shown comparable efficacy and clinical performance as low-dose OCs, with the advantage of not requiring daily dosing. Among the advantages of CVRs are their high effectiveness, good cycle control and the fact that they are user-controlled long-acting methods which provide a constant release of low doses of contraceptive steroids. Numerous studies have shown high acceptability among women, who report ease of use and the lack of a daily action as desirable
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