Long-acting Progestins: Promise and prospects
This article reviews the development, characteristics, and use of various types of long-acting progestins, examining their effectiveness, side effects, effects on reproduction, carcinogenicity, continuation, and acceptability. Progestins, synthetic hormones that act like the natural female hormone progesterone, can be administered in at least 5 different ways to provide pregnancy protection over extended periods: injectable contraceptives, hormone-releasing IUDs, subdermal implants, vaginal rings, and once-a-month oral pills. 3 progestins, medroxyprogesterone acetate in depot form (DMPA), norethindrone enanthate (NET EN), and levonorgestrel, have proven highly effective as long-acting contraceptives. Advantages of long-acting progestins are convenience and reversibility, while menstrual disturbances are a main disadvantage. The major unresolved question involves their possible carcinogenic effects. 2 injectables, NET EN and DMPA, have been used in about 100 countries. About 2.3 million women currently use DMPA, mainly in 3-month doses of 150 mg, especially in Jamaica, Thailand, Sri Lanka, and New Zealand. About 275,000 women use NET EN. DMPA and NET EN are highly effective, have few side effects apart from menstrual disturbances, and have noncontraceptive benefits such as increasing the supply of breast milk in lactating women and reducing the risk of pelvic infection. Continuation rates of injectables are about 50-75% at 1 year. DMPA has not been approved for use in the US because of concern over studies in which beagle dogs developed breast tumors and monkeys developed endometrial cancer while receiving high doses of these progestins. The relevance of these studies has been questioned, studies in humans using injectables show no increased risk of cancer, and several expert medical panels have endorsed the use of DMPA. Ongoing large, multicenter case-control studies should provide clearer answers; preliminary indications are that DMPA involves no additional risk for cervical or breast cancer. The main advantages of progestin-releasing IUDs are reduced menstrual bleeding and pain, but the devices cost more, must be replaced every year, cause spotting, and may be associated with more ectopic pregnancies than other IUDs. Implants, silastic or other polymer-based rods or capsules inserted under the skin, are very effective and can be used for up to 7 years. Vaginal rings are still under development. Other research is focusing on biodegradable implants, new injectables, once-a-month pill containing both estrogen and progestin, and hormonal methods for men.