Oral contraceptives and neoplasia: 1987 update

Combined OCs have been used by millions of women in the United States for more than 25 years. During this time, the steroid content of these pills has been markedly reduced from the high initial levels. All of the new formulations introduced in the past 15 years contain 50 μg or less of EE₂. The progestogen components are 1 mg or less of norethindrone, 1 mg ethynodiol diacetate, and 0.075 mg or less of levonorgestrel. Investigations in the past 6 years have contributed significant new knowledge to our understanding of the relationships between OCs and neoplasia. The pool of ever-users of OCs continues to grow substantially. The lag-time from first use is now well into and beyond the range accepted as necessary to promote carcinogenesis. The numbers of long-term users of OCs continue to grow. The investigate studies are much better able to define critical and confounding data items. The analyses of these data have become much more sophisticated and refined. In the United States, because of the suspected association with neoplasia in animals, the 17-hydroxyprogesterone are not in use. Reports of an association between sequential OCs and endometrial carcinoma have contributed to withdrawal of the sequential formulations from the United States market. The problems in investigating neoplasia and OCs include the following: (1) absence of a suitable animal model, (2) long lag-time from exposure to development of disease, (3) low incidence of specific neoplastic diseases, and (4) multiple etiologic factors in the study population. The pricipal investigative methods in the human being are various epidemiologic approaches. The methodologies most frequently used are (1) case reports (tumor registries), (2) disease rates and trends, (3) case-comparison (retrospective) studies, and (4) cohort (prospective) studies. These methods cannot prove a causal relationship between exposure to a possible carcinogen and the occurrence of disease. Case must be taken not to extrapolate epidemiologic conclusions to dissimilar populations. Consistent evidence (positive or negative) confirmed by multiple epidemiologic approaches, can be used to guide physicians and regulatory agencies in formulating policy for the clinical use of OCs.