Oral contraception: past, present, and future perspectives

Oral contraceptives (OCs) were initially approved for unrestricted use in 1960 in the United States and have been used and studied extensively for 30 years. The initial formulations contained a fixed dose of estrogen and progestogen ingested for 21 days, with a seven-day pill-free interval. Subsequent formulations contained a sequential estrogen dose, a progestogen alone given daily, and variable doses of both progestogen and estrogen. Although the estrogen and progestogen doses employed in currently marketed OCs are markedly lower than those used in the OCs of the 1960s and 1970s, the excellent contraceptive efficacy of these compounds has not been compromised. The estrogen component produces a dose-related increase in serum globulin concentrations, triglycerides, and high-density lipoprotein (HDL) cholesterol, along with a decrease in low-density lipoprotein (LDL) cholesterol, while the progestogen component causes peripheral insulin resistance, a decrease in HDL cholesterol, an increase in LDL cholesterol, and various androgenic effects. The effect of nicotine on thromboxane release acts synergistically with the elevated serum clotting factors to increase the incidence of both arterial and venous thrombotic events, particularly in women smokers over 35 years of age. However, there is no evidence of increased risk of myocardial infarction or stroke in healthy, nonsmoking women of any age who use OCs containing less than 50 micrograms estrogen. Likewise, the lower-dose estrogen/progestogen formulations do not have a clinically significant effect on glucose metabolism and have a neutral effect on lipoprotein metabolism. In addition, the many noncontraceptive health benefits associated with OCs are maintained with the lower-dose formulations. Thus, the low-dose formulations should improve the overall health of healthy, nonsmoking women as well as effectively prevent unwanted pregnancy.