PIP: There have been many reports of late regarding the safety and effectiveness of injectable contraceptives, yet there is still considerable confusion and uncertainty. The attempt is made in this discussion to clarify the issues by outlining the results of recent research in animal and human subjects. The current state of knowledge on injectable hormonal contraceptives is summarized. Attention is directed to the following: injectable preparations available for contraception; animal studies; human studies (pharmacology, effectiveness, bleeding problems, metabolic effects, neoplasia, return of fertility, and effects on progeny). Some data from animal studies have raised concern about the possible carcinogenicity of depot-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN), but certain animal models used appear to be inappropriate for studying the effects of these steroids in human subjects. A large number of clinical trials, including multicenter studies organized by the World Health Organization (WHO) have been carried out in many countries with both DMPA and NET-EN. The 2 steroid preparations have a similar mechanism of action in inhibiting gonadotropin production by the pituitary gland, which thus prevents ovulation. They do, however, show certain pharmacological differences. The differences in formulation are reflected in the levels of steroid found in the blood. From both DMPA and NET-EN the continuation rates have been found to vary markedly among different populations, ranging from 15% to nearly 90% at 1 year. Pregnancy rates (method failures) have been consistently low with DMPA, less than 1 pregnancy/100 woman years of use. The pregnancy rate reported with NET-EN has varied according to the interval between injections. A dose of 200 mg every 12 weeks resulted in a pregnancy rate considered to be unacceptably high (3.6/100 woman years) in 1 clinical trial undertaken by WHO. A more frequent administration of NET-EN in the same trial resulted in a pregnancy rate of less than 1/100 woman years at 18 months. The majority of women who receive DMPA or NET-EN experience some disruption of their normal menstrual cycle, defined as a cycle of 26-35 days' duration in which bleeding/spotting lasts for 2-8 weeks. Women frequently report irregular bleeding, spotting, and amenorrhea, but heavy or prolonged bleeding is uncommon. DMPA and NET-EN appear to be acceptable methods of fertility regulation.