Department of Gynecological Endocrinology, Beijing OB/GYN Hospital, Capital Medical University, Beijing, China.
Maturitas. 2012 Apr;71(4):337-44. doi: 10.1016/j.maturitas.2012.01.018. Epub 2012 Feb 24.
Dienogest (DNG) is a 19-nortestosterone derivative (a C-19 progestogen) with a cyanomethyl instead of an ethinyl group at the C-17 position, which may make the compound elicit fewer hepatic effects than other C-19 nortestosterone derivatives. Its similarity to norethisterone is reflected in its high endometrial efficacy, which could explain the high stability of the menstrual cycle women achieve when they use DNG in combination with ethinyl estradiol (EE) or with estradiol valerate (E2V). Its strong endometrial efficacy underlies the use of DNG (on its own) to treat endometriosis, and gives it antiproliferative and anti-inflammatory effects in the treatment of endometriotic lesions. Properties derived from its C-19 derivative structure include its short plasma half-life, of about 10h (which means the drug is not accumulated), and its high oral bioavailability, of more than 90%. However, DNG also has some of the properties of typical of progesterone derivatives, including a lack of effect on the metabolic and cardiovascular systems, and considerable antiandrogenic activity, the latter increased by its lack of affinity to the sex-hormone binding globulin (SHBG), in contrast to other C-19 progestogens. DNG has no glucocorticoid and no antimineralocorticoid activity. It also has no antiestrogenic activity, which suggests that it should not antagonize estradiol's beneficial effects. This is important for its use in the treatment of endometriosis, because, due to DNG's low gonadotropic activity, E2 levels are not decreased to zero, in contrast to treatments with gonadotropin-releasing hormone (GnRH) analogues. This maintenance beneficial E2 effects is of particular importance for the general tolerability of the first contraceptive pill to use E2V instead of EE, although clinical endpoint studies are still ongoing. These studies are expected, on the basis of its pharmacology, to demonstrate the cardiovascular safety of the new pill.
地诺孕素（DNG）是一种 19-去甲甾体化合物（C-19 孕激素），在 C-17 位用氰甲基取代了乙炔基，这可能使该化合物比其他 C-19 去甲甾体衍生物引起更少的肝脏作用。它与炔诺酮的相似之处反映在其对子宫内膜的高疗效上，这可以解释当妇女使用 DNG 与炔雌醇（EE）或与戊酸雌二醇（E2V）联合使用时，她们的月经周期能够达到的高稳定性。其对子宫内膜的强大疗效使得 DNG（单独使用）能够用于治疗子宫内膜异位症，并在治疗子宫内膜异位症病变时具有抗增殖和抗炎作用。源自其 C-19 衍生物结构的特性包括其较短的血浆半衰期，约为 10h（这意味着药物不会积累），以及其较高的口服生物利用度，超过 90%。然而，DNG 也具有一些典型孕激素衍生物的特性，包括对代谢和心血管系统没有影响，以及相当大的抗雄激素活性，后者由于其缺乏与性激素结合球蛋白（SHBG）的亲和力而增加，与其他 C-19 孕激素不同。DNG 没有糖皮质激素和盐皮质激素活性。它也没有抗雌激素活性，这表明它不应拮抗雌二醇的有益作用。这对于其在子宫内膜异位症治疗中的应用很重要，因为由于 DNG 的低促性腺激素活性，E2 水平不会降低到零，与使用促性腺激素释放激素（GnRH）类似物的治疗相反。由于 DNG 的低促性腺激素活性，E2 水平不会降低到零，与使用促性腺激素释放激素（GnRH）类似物的治疗相反。由于 DNG 的低促性腺激素活性，E2 水平不会降低到零，与使用促性腺激素释放激素（GnRH）类似物的治疗相反。由于 DNG 的低促性腺激素活性，E2 水平不会降低到零，与使用促性腺激素释放激素（GnRH）类似物的治疗相反。这维持了 E2 的有益作用，对于第一避孕药使用 E2V 代替 EE 的一般耐受性特别重要，尽管仍在进行临床终点研究。根据其药理学，这些研究有望证明新避孕药的心血管安全性。
