Corson S L
Philadelphia Fertility Institute, Pennsylvania Hospital, University of Pennsylvania School of Medicine.
Acta Obstet Gynecol Scand Suppl. 1990;152:25-31. doi: 10.3109/00016349009156503.
The search for a highly selective progestin that exerts a potent and targeted progestational response with minimal or absent androgenic effect has paralleled investigation into the possible impact of these agents on cardiovascular disease in women. Such a progestin, norgestimate (NGM), in a dose of 250 micrograms, has been combined with ethinyl estradiol (EE) 35 micrograms in a new oral contraceptive (OC), Ortho-Cyclen or Cilest. Results of two long-term, multicentric clinical trials demonstrate that this formulation is comparable in efficacy to the norgestrel-containing OC Lo/Ovral. There were no statistically significant differences in pregnancy rate, and both OCs were well-tolerated in a large and diverse study population. In several areas, however, the inherently lower androgenicity of the norgestimate OC produced clinical changes compared with the norgestrel formulation. These changes were primarily evident in the more natural menstrual patterns with the norgestimate OC, its less severe impact on the endometrium, and, most important, its positive impact on lipoprotein metabolism. NGM/EE consistently produced statistically significant increases in high density lipoprotein (HDL) and concomitant improvement in the ratio of low density lipoprotein (LDL) to HDL. By cycle 24, this highly predictive parameter of atherosclerotic risk had decreased 7.7% in the NGM/EE group. Conversely, the norgestrel-containing formulation resulted in statistically significant decreases in HDL and increases in the LDL/HDL ratio; by cycle 24, these patients showed an 18.5% increase in the LDL/HDL ratio. All between regimen comparisons of mean changes in the LDL/HDL ratio were statistically significant, from baseline through cycles 3, 6, 12 and 24.
寻找一种具有高度选择性的孕激素，使其在发挥强大且靶向性孕激素作用的同时，雄激素作用最小或不存在，这与对这些药物对女性心血管疾病可能影响的研究是并行的。这样一种孕激素——诺孕酯（NGM），剂量为250微克，已与35微克炔雌醇（EE）联合用于一种新型口服避孕药（OC），即 Ortho-Cyclen 或 Cilest。两项长期、多中心临床试验的结果表明，该制剂在疗效上与含炔诺孕酮的口服避孕药 Lo/Ovral 相当。妊娠率无统计学显著差异，并且在一个庞大且多样化的研究人群中，两种口服避孕药的耐受性都良好。然而，在几个方面，与炔诺孕酮制剂相比，诺孕酯口服避孕药固有的较低雄激素活性产生了临床变化。这些变化主要体现在诺孕酯口服避孕药更自然的月经模式、对子宫内膜较轻的影响，以及最重要的是对脂蛋白代谢的积极影响上。NGM/EE 持续使高密度脂蛋白（HDL）产生统计学显著升高，并使低密度脂蛋白（LDL）与 HDL 的比率得到改善。到第24周期时，这个动脉粥样硬化风险的高度预测参数在 NGM/EE 组降低了7.7%。相反，含炔诺孕酮的制剂导致 HDL 统计学显著降低，LDL/HDL 比率升高；到第24周期时，这些患者的 LDL/HDL 比率升高了18.5%。从基线到第3、6、12和24周期，所有方案之间 LDL/HDL 比率平均变化的比较均具有统计学显著性。
