PIP: Sex hormones play an important role in the control of glucose metabolism and insulin. Decreased glucose tolerance observed at the end of pregnancy in most cases remains within normal limits. Pregnancy has an important effect on the islets of Langerhans and on the growth of beta cellules. At the end of pregnancy, assimilation of glucose and triglycerides by maternal tissues is slowed and transfer to the fetus is favored. Hyperinsulinism persists but insulin resistance at the level of maternal tissue becomes very strong and the number of receptors declines. This late pregnancy insulin resistance has not been satisfactorily explained. The declining number of receptors may be a mechanism, or the "antiinsulin" pregnancy hormones which includes estrogens and progesterone may play a major role. Although other mechanisms have been proposed to explain the antiinsulin effect, the role of sex hormones and especially of progesterone (and synthetic progestins used in contraception) appears crucial. The presence of estrogen and progesterone receptors in the beta cellules of the islets of Langerhans suggests a direct effect of these hormones on the cellules. Estrogens however work by other mechanisms than insulin secretion. Experimental evidence indicates that during pregnancy, progesterone increases insulin release while human placental lactogen stimulates hyperplasia of the islets. The progestins derived from progesterone used in contraception have a parallel action. A slight elevation of blood sugar and insulinemia have been observed in oral contraceptive (OC) users. Only 3-5% of OC users develop true hyperglycemia. The changes are usually transitory and disappear on termination of OC use except in the small number of women predisposed to diabetes. The decreased glucose tolerance of OC users differs from true diabetes. Combined OCs favor vascular accidents and myocardial infarct in insulin-dependent diabetics. The mechanisms involved include deteriorating control of diabetes; effects on the serum lipids, coagulation factors, and blood pressure; and direct effects of estrogen on the vascular wall. Venous but not arterial vascular accidents decline with lower estrogen doses. Progestins probably play a more significant role from estrogens in decreasing glucose tolerance. Pregnanes, progestins derived from progesterone, do not appear to affect glucose tolerance. Among testosterone derivatives, the entrances decrease glucose tolerance slightly and the gonanes more strongly, also causing hyperinsulinism. But the new triphasic OCs with low levonorgestrel doses cause no significant changes in glucose tolerance even in women with histories of gestational diabetes. Long-acting progestin implants, vaginal rings, and injectables appear thus far to have minimal or no effects on glucose tolerance.