Contraceptive devices: intravaginal and intrauterine delivery systems

Substances with an antifertility activity can be delivered directly into the vagina and the uterus. Indeed, it has been known for decades that the vaginal mucosa is an excellent way through which to deliver a number of compounds to the general circulation. Research and development efforts have concentrated on rings delivering only progestins, or both an estrogen and a progestin. The only combined ring marketed so far releases 15 microg ethynyl estradiol and 120 microg etonogestrel, and has a failure rate between one and two per 100 women-years of use. It has a preset duration of action of 1 month, has to be inserted before day 5 of the cycle, irrespective of the presence of menstrual flow, and withdrawn after 21 days, thereby allowing proper cycle control. Among rings releasing only a progestin, one device releasing progesterone has been marketed; all others are still under development. Unlike other long-term methods, vaginal rings do not require the involvement of a healthcare professional and can be inserted and removed by the user. The first attempt at achieving contraception by inserting a device in the uterus is 100 years old. Half a century later, medicated intrauterine systems were investigated; they are superior to inert devices and today a number of active principles, such as copper and progestogens, have been incorporated and tested when released from an intrauterine device (IUD). Copper-releasing devices last more than 10 years, with cumulative pregnancy rates of between approximately 5 and 3, and cumulative expulsion rates between approximately 12 and 8. With all IUDs, bleeding and pain are the most common reasons for a request to withdraw a device. There is agreement that fertility after removal of a copper-IUD is not impaired. Finally, the overall risk of ectopic pregnancy is reduced in IUD users, compared with using no contraception. The first progestogen-releasing system contained progesterone, had 1-year duration of action and was marketed some 30 years ago; unfortunately, it was shown that failure caused an increase of extrauterine pregnancies. This potentially dangerous effect eventually led to the withdrawal of the device from the market. In the meantime, a device releasing the synthetic progestin levonorgestrel was being developed and has now been successfully marketed; it lasts for a minimum of 5 years and, although absorbed systemically, cyclic function is maintained. The system is one of the most effective methods of contraception available today: large clinical studies indicate a Pearl index of 0.1 per 100 woman-years. Although a postfertilization effect cannot be excluded, in a majority of cases, intrauterine systems act as true contraceptives, preventing fertilization.