PIP: The clinical and epidemiological literature is reviewed as to metabolic effects of oral contraceptives (OCs). Both the estrogens and the progestins in OCs cause biochemical alterations which have metabolic consequences. Changes in glucose, lipid, and protein metabolism suggest that the dosage of both estrogens and progestins should be minimized as much as possible. All studies with OCs show no changes in glucose tolerance, but all do consistently show elevated plasma insulin levels as a result of OC usage. This occurs because the pill causes a decrease in insulin sensitivity in healthy women. Increases in age and weight, regardless of OC usage, will also cause an increase in glucose tolerance. Oral glucose tolerance deteriorates in all OC user groups, the greatest deterioration being in the high-dose estrogen users. Women with a history of gestational diabetes or impaired glucose tolerance should be considered high-risk pill users. Lipid abnormalities as a result of pill usage are primarily due to estrogen content. Fasting triglyceride levels are increased in all estrogen users. High-risk factors to be considered in OC prescription are: moderate obesity; diabetes; history of gestational diabetes; hypertension; history of pancreatitis, gallbladder or liver disease; physical evidence of xanthomatosis; age over 30 and smoker; age over 35; family history of hyperlipidemia; and family history of early atherosclerotic vascular disease. Many of the pill-induced protein synthesis changes are similar to those which occur during pregnancy. These, too, are due to estrogen content.