Progestins Progestins are synthetic compounds that mimic the effect of natural progesterone but differ from it structurally. The progestins differ from one another in their affinities for estrogen, androgen, and progesterone receptors; their ability to inhibit ovulation; and their ability to substitute for progesterone and to antagonize estrogen. Some are directly bound to the receptor (levonorgestrel, norethindrone), whereas others require bioactivation as, for example, desogestrel, which is converted in the body to its active metabolite, etonogestrel. The 17-acetoxy progestins (e.g., medroxyprogesterone acetate) are bound by the progesterone receptor. Norgestrel exists as two stereoisomers, identified as dextronorgestrel and levonorgestrel. Only levonorgestrel is biologically active. Three newer progestins (norgestimate, desogestrel, and gestodene) are viewed as more “selective” than the other 19-nor progestins, in that they have little or no androgenic effect at doses that inhibit ovulation (109). The FDA approved norgestimate-and desogestrelcontaining OCs, and gestodene is available in Europe. Gestodene is a derivative of levonorgestrel that is more potent than the other preparations (i.e., very little of it is required for antifertility effects). Similarly, norelgestromin is an active metabolite of norgestimate and more potent than the parent compound. It is used in the transdermal patch. Drospirenone, a progestin introduced in the United States, is a derivative of the diuretic spironolactone. It has high affinity for progesterone receptors, mineralocorticoid receptors, and androgen receptors. It acts as a progesterone agonist but is a mineralocorticoid antagonist and androgen antagonist (110). Comparative studies suggest a small decrease in body weight and in blood pressure, with equivalent cycle control and contraceptive efficacy, in women taking an OC containing 3 mg of drospirenone/30 μg ethinyl estradiol versus women taking a 150 μg levonorgestrel/30 μg ethinyl estradiol (EE) preparation (111). Pilot studies of women with polycystic ovary syndrome showed good cycle control and reduction in androgen levels with no change in weight, blood pressure, or glucose metabolism (112). The FDA approved the 20 μg EE/3 mg drospirenone OC for premenstrual dysphoric disorder (PMDD) in women who choose OCs for contraception. When compared to an OC with 30 μg EE/150 μg levonorgestrel, women taking the drospirenone OC had better relief of menstrual symptoms, better improvement in acne, reduction in negative affect during the menstrual phase, and a greater feeling of well-being (113). Dienogest, another progestin introduced in the United States, is combined with estradiol valerate, not ethinyl estradiol. Whether it offers any advantage over already marketed OC combinations is not yet evident. The dienogest/estradiol valerate combination is as effective as levonorgestrel/ethinyl estradiol as a contraceptive, and in treating abnormal uterine bleeding (114).