Oral contraceptives: an epidemiological perspective.

Oral contraceptives (OCs) containing a fixed dose of estrogen and progestogen in a 21-day regimen initially were approved for unrestricted use in the 1960s in the United States. OCs have been used and studied extensively for more than 30 years. They have always been seen as providing excellent efficacy. However, estrogens were associated with major risks in the use of OCs. In the early 1960s, case reports of thromboembolism in women using OCs led to epidemiological studies suggesting a correlation between deep vein thrombosis and the estrogen content of the pill. Research focused on decreasing the estrogen dose. In the evolution process, the combination monophasics of the early 1960s gave way to the sequential pill and the "mini pill" of the 1970s. Sex steroids given in the form of OCs were shown to alter lipoprotein and carbohydrate metabolism. This, together with the increased risk of thromboembolism, led to increased risk of cardiovascular disease, e.g., myocardial infarction. Little consideration (in the early 1960s) was given to the effects of potent progestogens and their interaction with estrogens. Hence, the recent focus of clinical research is the development of new and improved progestational agents. These third-generation gonane types appear to have little impact on carbohydrate or lipoprotein metabolism while maintaining excellent efficacy and cycle control. They should reduce the risk of serious side effects. However, to understand how and why these agents evolved, tracing the history of OC development is valuable. It might allow us to determine the baseline dose where we will begin to lose some of the OCs' benefits.