Effect of progestins on glucose and lipid metabolism

Abstract

Gestamimetic amounts of progesterone enhance basal and glucose-stimulated insulin production. Contraceptive doses of synthetic progestins cause a moderate increase or no change in glucose-stimulated insulin production, depending on route of administration and species tested. Estrogens potentiate the insulinotropic effects of progesterone and the synthetic progestins. Basal serum triglyceride concentrations are generally unaffected by progesterone or 17 alpha-acetoxyprogesterone treatment but may decrease during 19-nortestosterone administration. Glucose tolerance does not change during treatment with gestamimetic doses of progesterone alone but may improve in rats and monkeys during concurrent estrogen administration. By contrast, deterioration of glucose tolerance is observed in women treated concurrently with synthetic estrogen plus 19-nortestosterone derivatives and, occasionally, with 19-nortestosterone derivatives alone. No consistent changes in glucose metabolism have been observed after treatment with 17 alpha-acetoxyprogesterone derivatives alone. The cause of the species-related differences in glucose metabolism during 19-nortestosterone treatment is obscure.

PIP: Literature on the effect of progestins on glucose and lipid metabolism is reviewed. Progesterone, in doses mimicking pregnancy, enhances basal and glucose-stimulated insulin production. Synthetic progestins, in contraceptive doses, have no effect, or produce a moderate increase in glucose-stimulated production, depending on the route of administration and the species studied. The insulinotropic effects of progesterone and synthetic progestins are potentiated by estrogens. Generally, basal serum triglyceride concentrations are unaltered by progesterone or 17alpha-acetoxy-progesterone, though they may be decreased by 19-nortestosterone. Progesterone, in doses mimicking pregnancy, does not affect glucose tolerance. However, the concurrent administration of estrogen may improve glucose tolerance in rats and monkeys. Conversely, the administration of synthetic estrogen in combination with 19-nortestosterone derivatives impairs glucose tolerance in women; in some cases, 19-nortestosterone derivatives alone also have this effect. No consistent alterations in glucose metabolism have been observed with 17alpha-acetoxyprogesterone derivatives alone. The reasons for the species-related differences in glucose metabolism during treatment with 19-nortestosterone remains to be elucidated.