Preclinical profiles of progestins used in formulations of oral contraceptives and hormone replacement therapy

Progestins used in oral contraceptive formulations available in the United States include norgestimate, desogestrel, norethindrone, norethindrone acet ate, and levonorgestrel. Progestins used in the United States in continuous and intermittent formulations of hormone replacement therapy are norgestim ate, medroxyprogesterone acetate, and norethindrone acetate. The chemical s tructure of a progestin determines its relative binding affinity for the pr ogesterone and androgen receptors, as well as the sex hormone binding globu lin in human serum, and determines its clinical profile. Overall, the prope rties of levonorgestrel or norethindrone acetate in this regard differ from norgestimate and are more conducive to androgenic stimulation. Estrogen re placement offers cardio protective effects in postmenopausal women. Progest ins are added to hormone replacement therapy to counteract the well-known I ncreased risk of endometrial hyperplasia associated with use of unopposed e strogen. Animal models show that for some parameters, including improvement of lipid profiles, progestins can diminish the cardioprotective effect of estrogen. Initial animal studies of norgestimate combined with estrogen do not show an attenuation of estrogenic effects.