Kafrissen M E
R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869-0602.
Am J Obstet Gynecol. 1992 Oct;167(4 Pt 2):1196-202. doi: 10.1016/s0002-9378(12)90411-1.
Despite the well-documented efficacy and safety of low-dose oral contraceptives, the development of newer formulations containing highly selective progestins with minimal or no androgenic activity has been a goal of pharmaceutical research. The efficacy and safety of norgestimate, a progestin with inherently low androgenicity, in combination with ethinyl estradiol, has been examined in several phase II and phase III clinical studies, and these are reviewed. Norgestimate/ethinyl estradiol has proved to be a low-dose oral contraceptive with high selectivity that provides the cycle control of older oral contraceptive formulations with comparable efficacy. Results of comparison studies between norgestimate/ethinyl estradiol and formulations containing norgestrel, a progestin with relatively greater androgenic activity, in combination with ethinyl estradiol, are reported for effects on lipid and lipoprotein levels and carbohydrate metabolism. Norgestimate/ethinyl estradiol consistently produced statistically significant increases in high-density lipoprotein cholesterol and improvement in the ratio of low-density lipoprotein cholesterol to high-density lipoprotein. In contrast, norgestrel/ethinyl estradiol produced statistically significant decreases in high-density lipoprotein cholesterol and potentially adverse changes in the low-density/high-density lipoprotein ratio. Phase II studies have confirmed that norgestimate/ethinyl estradiol has low androgenic activity and causes minimal effect on coagulation factors and carbohydrate metabolism.
尽管低剂量口服避孕药的疗效和安全性已有充分记录，但开发含有高选择性孕激素且雄激素活性最小或无雄激素活性的新型制剂一直是药物研究的目标。去氧孕烯炔雌醇片（一种本质上雄激素活性较低的孕激素）与炔雌醇联合使用的疗效和安全性已在多项II期和III期临床研究中得到检验，现对此进行综述。去氧孕烯炔雌醇片已被证明是一种具有高选择性的低剂量口服避孕药，能提供与传统口服避孕药相当的周期控制效果。本文报告了去氧孕烯炔雌醇片与含左炔诺孕酮（一种雄激素活性相对较高的孕激素）和炔雌醇的制剂在脂质和脂蛋白水平以及碳水化合物代谢方面的比较研究结果。去氧孕烯炔雌醇片持续使高密度脂蛋白胆固醇有统计学意义的升高，并改善低密度脂蛋白胆固醇与高密度脂蛋白的比值。相比之下，左炔诺孕酮炔雌醇片使高密度脂蛋白胆固醇有统计学意义的降低，并使低密度/高密度脂蛋白比值发生潜在的不利变化。II期研究证实，去氧孕烯炔雌醇片雄激素活性低，对凝血因子和碳水化合物代谢的影响最小。
