Abstract
Abstract In 1960, the first hormonal contraceptive agent, Enovid approved by the Food and Drug Administration in the United States. The pill contained mestranol 150 mcg and norethynodrel 10 mg. High dose pills containing >50 mcg of estrogen were discontinued in 1988 due to a higher risk of myocardial infraction and stroke secondary to thrombosis. Until recently, the only estrogens used in combination OCPs were mestranol and ethinyl estradiol (EE). Estetrol (E4) and 17-beta estradiol have been added to newer pill and intravaginal ring (IVR) formulations in order to reduce the risk of thrombosis. Progestins confer the primary contraceptive effect in combination agents and can be used without estrogens. First generation progestins include norethynodrel, ethynodiol diacetate, norethindrone and norethindrone acetate (estranes). Second generation progestins include norgestrel and levonorgestrel (gonanes). Third generation include gestoden, desogrestrel and norgestimate, which are less androgen versions of the second generation progestins. Fourth generation progestins have no androgenicity include drospirenone. The fourth generation progestin is a 17 carbon compound which separates it from the other progestins that are primarily 19 carbon derivatives of androgens. Segesterone acetate (SA) is a newer progestin that is less potent and has no androgenic properties. SA, combined with EE, is currently being used in an IVR. However, clinical trials are ongoing using SA with 17-beta estradiol in an IVR and another with EE as a contraceptive gel. Other new methods of hormonal contraception include progestins in a biodegradable implant, longer acting injectables that can last 6-12 months, transdermal patches that are imbedded with an array of microneedles where either the contraceptive agent is in a reservoir or in the needles themselves. Microchip technology is being developed by the Gates Foundation that would allow levonorgestrel to be released systemically at will over a 16-year period using a remote device. Multipurpose technologies are being developed utilizing contraceptive pills, injectables and IVRs containing hormonal agents as well as medications to prevent STI/HIV acquisition.
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