PIP: 3 large classes of progestins are used in current combined oral contraceptives (OCs): estranes, gonanes, and pregnanes. Estranes, including norethisterone acetate, lynestrenol, norethynodrel, and ethynodiol diacetate, are all related to the base norethisterone and must be metabolized to norethisterone to be active. The gonanes, principally represented by norgestrel, are similar in structure to norethisterone, but the methyl radical is replaced by an ethyl group. At equal weight, norgestrel is much more powerful than norethisterone. The active part of norgestrel is its dextro-isomer, levonorgestrel. The pregnanes include derivatives of 17-hydroxy-progesterone, of which only cyproterone acetate is currently used in contraception. 6 large groups of combined oral contraceptives evaluated for their impact on carbohydrate and lipid metabolism contained the following: 1) 75-150 mcg of ethinyl estradiol and an estrane 2) a moderate dose (50 mcg) of estrogen and a pregnane 3) a moderate dose of estrogen and an estrane 4) a moderate dose of estrogen and 250 mcg levonorgestrel 5) a low dose (30 mcg) estrogen and 250 mcg norgestrel, and 6) a low dose of ethinyl estradiol and 150 mcg levonorgestrel. The studies demonstrated impairment of glucose tolerance in OC users, whose levels of serum insulin and pyruvate increased. The greatest deterioration in glucose tolerance was found in high dose estrogen pills, but the greatest decrease in insulin secretion was found in a pill containing levonorgestrel. Most of the pills significantly decreased the fasting plasma glucose levels and decreased glucose tolerance, with the maximum effect found in pills with high estrogen contents. Insulin secretion increased, with the 3 pills containing levonorgestrel showing the greatest effect. Pills containing levonorgestrel provoked a greater insulin resistance than that of other combined pills. Since insulin resistance is a recognized metabolic effect of progesterone itself and of progestins used in contraception, and since the clinical effects of prolonged insulin resistance are unknown, but may include early atherosclerosis, it appears that OC formulations provoking the least insulin resistance should be preferred; formulations containing norethisterone therefore appear preferable to those containing norgestrel. Another study compared the effects on serum lipids of 4 groups of OCs containing 30 mcg estrogen and 250 mcg or 150 mcg of levonorgestrel, 50 mcg of estrogen and 1 mg norethisterone acetate, and 20 mcg estrogen and 1 mg norethisterone acetate. OCs with levonorgestrel reduced serum cholesterol levels significantly, while OCs with norethisterone acetate had the highest serum triglyceride levels. OCs with levonorgestrel but not those with norethisterone acetate reduced high density lipoprotein (HDL) cholesterol. Pills containing 250 mcg levonorgestrel lowered the ratio of HDL2/low density lipoprotein (LDL) significantly. Carbohydrate and lipid metabolic effects were found to depend on the dose of estrogen and the dose and type of progestin. Among the pills studied, 1 containing 30-35 mcg estrogen and 1 mg norethisterone acetate gave the best results on the parameters studied.