Foidart Jean Michel, Gemzell-Danielsson Kristina, Kubba Ali, Douxfils Jonathan, Creinin Mitchell D, Gaspard Ulysse
Department of Obstetrics and Gynecology, University of Liège, Liège, Belgium (Prof Foidart and Prof Gaspard).
Estetra SRL, an affiliate company of Mithra Pharmaceuticals, Liège, Belgium (Prof Foidart).
AJOG Glob Rep. 2023 Sep 18;3(4):100266. doi: 10.1016/j.xagr.2023.100266. eCollection 2023 Nov.
Ethinylestradiol and drospirenone combined oral contraceptive formulations have been marketed for >20 years. Drospirenone has antimineralocorticoid and anti-androgenic effects that may offer several health benefits. Recently, 2 new drospirenone-containing oral contraceptives entered the market, 1 as a progestin-only pill containing 4 mg drospirenone and the other as a combined oral contraceptive containing 15 mg estetrol and 3 mg drospirenone. Estetrol has a unique differential effect on nuclear and membrane estrogen α-receptors when compared with other estrogens, leading to low impact on the liver, breast, and hemostasis parameters and a beneficial effect on the endometrium, vagina, cardiovascular system, bone, and brain. Phase 3 clinical studies demonstrated that the Pearl Index (pregnancies per 100-woman-years) for drospirenone alone is 4.0 in the United States and 0.93 in the European Union and for the estetrol-drospirenone combination it is 2.65 and 0.44, respectively. Drospirenone alone demonstrates high rates of unscheduled bleeding and low rates of scheduled bleeding, whereas the estetrol-drospirenone combination demonstrates a predictable and regular bleeding profile for most users with a high stable rate of scheduled bleeding and a low rate of unscheduled bleeding, reported primarily as spotting only. The adverse event profiles and discontinuation rates owing to adverse events are comparable, and no clinically significant effects were observed on metabolic parameters with either product. Hemostatic assays for drospirenone do not fully evaluate all parameters although the testing that is available suggests negligible effects, whereas validated hemostatic assays demonstrate that the estetrol-drospirenone combination has limited impact on hemostasis. The introduction of 4 mg drospirenone and 15 mg estetrol with 3 mg drospirenone are valuable additions to the contraceptive market. Adding estetrol to 3 mg drospirenone provides advantages of contraceptive efficacy and a regular, predictable bleeding profile with minimal impact on hemostasis parameters.
炔雌醇和屈螺酮复方口服避孕药制剂已上市超过20年。屈螺酮具有抗盐皮质激素和抗雄激素作用，可能带来多种健康益处。最近，两种含屈螺酮的新型口服避孕药进入市场，一种是仅含4mg屈螺酮的孕激素避孕药，另一种是含15mg雌三醇和3mg屈螺酮的复方口服避孕药。与其他雌激素相比，雌三醇对核雌激素α受体和膜雌激素α受体具有独特的差异作用，对肝脏、乳腺和止血参数影响较小，对子宫内膜、阴道、心血管系统、骨骼和大脑具有有益作用。3期临床研究表明，在美国，单独使用屈螺酮的 Pearl指数（每100名妇女年妊娠数）为4.0，在欧盟为0.93；对于雌三醇 - 屈螺酮组合，分别为2.65和0.44。单独使用屈螺酮时，非计划出血发生率高，计划出血发生率低，而雌三醇 - 屈螺酮组合对大多数使用者显示出可预测且规律的出血模式，计划出血稳定率高，非计划出血发生率低，主要表现为点滴出血。两种产品的不良事件谱和因不良事件导致的停药率相当，且未观察到对代谢参数有临床显著影响。尽管现有检测表明屈螺酮对止血的影响可忽略不计，但屈螺酮的止血检测并未全面评估所有参数，而经过验证的止血检测表明雌三醇 - 屈螺酮组合对止血的影响有限。4mg屈螺酮以及15mg雌三醇与3mg屈螺酮的组合进入避孕药市场具有重要价值。在3mg屈螺酮中添加雌三醇具有避孕效果好、出血模式规律可预测且对止血参数影响最小等优点。
