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词汇介绍
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解析
Cyproterone 英/saɪ'prɑtə,ron/
释 义 n. 环丙孕酮
例 句 Objective To establish an accurate method for dissolution test of cyproterone acetate tablets. 目的建立准确测定复方醋酸环丙孕酮片溶出度的方法。
概述
概述
环丙孕酮,是一种甾体类抗雄激素药,在1960年代和1970年代进行了研究,但从未引入医学领域。这是一个模拟的醋酸环丙孕酮(CPA)、抗雄激素、孕激素、以及抗促性腺激素,环丙孕酮和CPA是最早开发的抗雄激素药与CPA不同,该药物从未销售过医疗用途。环丙孕酮是第一个被开发的纯抗雄激素,以及此类紧随其后的其他药物,包括甾体类抗雄激素贝诺酮和BOMT以及非甾体类抗雄激素氟他胺。环丙孕酮,也被称为1α,2α亚甲基-6-氯17α羟基δ6孕酮,是一种合成的孕激素和衍生物的孕酮,它是CPA 的游离醇或17α- 脱乙酰基类似物。
药理学
环丙孕酮是一种有效的抗雄激素药,与CPA相似。但是,相对于CPA,它作为雄激素受体(AR)的拮抗剂的功效要低大约三倍。与CPA一样,环丙孕酮实际上是AR的弱部分激动剂,因此在某些情况下具有抗雄激素和雄激素活性的潜力。与CPA(一种高效的孕激素)不同,环丙孕酮是一种纯的抗雄激素药,实际上没有孕激素的活性。由于环丙孕酮在雄性动物中的促前列腺作用,与雄性啮齿动物不同,已发现环丙孕酮在雄性啮齿动物中会增加睾丸重量,增加A型精原细胞的总数,增加Sertoli细胞的总数,过度刺激Leydig细胞,而且对精子发生几乎没有影响。相反,也有报道说雄性啮齿动物的精子发生受到抑制,性腺的副重量(例如前列腺,精囊)和生育能力受到抑制。尽管可以在停止治疗后迅速恢复,但仍显着减少。与CPA不同,由于环丙孕酮缺乏孕激素和促性腺激素的活性,因此它不能抑制女性的排卵。CPA和环丙孕酮在动物中均具有一些弱的糖皮质激素活性,并抑制肾上腺和脾脏重量,其中CPA 在小鼠中的功效约为泼尼松的五分之一。与CPA不同,环丙孕酮似乎在体外对17β-羟类固醇脱氢酶和5α-还原酶具有 抑制作用。与CPA相反,环丙孕酮对阿片受体没有亲和力
临床研究
在临床研究中,发现环丙孕酮作为抗雄激素药的功效远低于CPA,这在很大程度上是由于其缺乏伴随的促性腺激素作用。Bierich(1970,1971)研究了环丙孕酮作为性早熟的一种治疗方法,但未见明显改善。在男性中,每天100mg环丙孕酮在治疗痤疮方面被证明是无效的,据推测与痤疮的促性腺激素作用及其抗雄激素活性的抵消有关。然而,对于睾丸激素水平低得多且药物没有促性腺激素活性的妇女,在开始治疗后的2至4周内,每天口服100到200 mg环丙孕酮可以有效减少所有患者的皮脂生成。相反,局部使用环丙孕酮的效果远不如安慰剂。
另一项研究表明,每天服用100 mg环丙孕酮对高雄激素血症女性减少皮脂产生的效果不明显。同样,该药物在治疗女性多毛症方面也显示出令人失望的结果,仅在有限的病例中出现明显的有效作用。在同一研究中,痤疮的减少效果更好,但明显不及CPA所产生的痤疮,只有脂溢性改善才被认为是令人满意的。与环丙孕酮相比,口服环丙孕酮避孕药可导致痤疮和皮脂溢的改善。
醋酸环丙孕酮或螺内酯降低接受雌二醇治疗的变性人的睾酮浓度
发表时间:2019-06-01
影响指数:2.5
作者: Lachlan Angus
期刊:Endocr Connec
Rapid rises in demand for transgender health services have been observed worldwide. Birth-assigned males who wish to transition to female (hereafter termed transfeminine individuals) are typically treated with oestradiol as feminising gender-affirming hormone therapy. Goals of therapy are generally to increase serum oestradiol concentrations and lower serum total testosterone concentrations to achieve sex steroid concentrations in the female reference range. Over 3-24 months, this leads to feminine physical characteristics including softening of skin, a decrease in facial and body hair growth, changes in body fat and muscle distribution, as well as breast development. Oestradiol improves psychological functioning in transfeminine individuals; however, oestradiol alone is usually insufficient to lower serum total testosterone concentrations from a male to a female reference range. Oestradiol suppresses gonadotropin-releasing hormone (GnRH) via negative feedback, in turn partially lowering testosterone. However, as the majority of individuals (82% in our clinics) do not undergo genital reassignment surgery to remove the testes, which are responsible for >95% of testosterone production, most individuals will require treatment with an additional anti-androgen drug. Anti-androgens such as cyproterone acetate or spironolactone are commonly added to oestradiol, lowering or blocking the effects of testosterone to aid development of feminising physical characteristics. In transfeminine individuals wishing to inhibit androgenic physical characteristics, choice of antiandrogen agent is a common clinical scenario faced by patients and treating clinicians alike. Whilst both antiandrogen agents, cyproterone acetate and spironolactone, have been shown to lower serum testosterone concentrations if added to oestradiol treatment, there is little evidence to guide the superiority of one antiandrogen over another. Both cyproterone acetate and spironolactone have peripheral anti-androgen effects, but cyproterone acetate additionally has progestogenic actions which may be more effective in suppressing GnRH and in turn, testosterone concentrations.
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