十一酸雌二醇

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十一酸雌二醇
临床资料
读音shí yī suān cí èr chún（汉语拼音）
商品名（英语：Drug nomenclature）Delestrec, Progynon Depot 100, 以及其他
其他名称EU;E2U;
雌二醇十一酸酯;十一酸雌酮;十一烷酸雌二醇
（商品代号）RS-1047;SQ-9993
给药途径肌注[1]
药物类别（英语：Drug class）雌二醇； 雌二醇酯
ATC码
法律规范状态
法律规范
  • 处方药（℞-only）
药物动力学数据
生物利用度肌注（IM ）：接近100%[2]
口服：同口服雌激素药物（英语：Pharmacokinetics of estradiol），约为5%[3][4]
血浆蛋白结合率Estradiol: ~98% (到白蛋白和SHBG)[2][5]
药物代谢在肝脏、血液和组织中通过酯酶的裂解[6][4]
代谢产物雌二醇，十一酸，雌二醇代谢物[6][4]
生物半衰期不确定
作用时间肌注（IM ）:
• 10–12.5 mg: 1–2 月[7][8]
• 25–50 mg: 2–4 月[9]
排泄途径尿液
识别信息
  • [(8R,9S,13S,14S,17S)-3-羟基-13-甲基-6,7,8,9,11,12,14,15,16,17-十氢环戊[a]苯并[a]烯-17-基]十一酸酯
CAS号3571-53-7  checkY
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)
ECHA InfoCard100.020.616 编辑维基数据链接
化学信息
化学式C29H44O3
摩尔质量440.67 g·mol−1
3D模型（JSmol（英语：JSmol））
  • CCCCCCCCCCC(=O)O[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=C3C=CC(=C4)O)C
  • InChI=1S/C29H44O3/c1-3-4-5-6-7-8-9-10-11-28(31)32-27-17-16-26-25-14-12-21-20-22(30)13-15-23(21)24(25)18-19-29(26,27)2/h13,15,20,24-27,30H,3-12,14,16-19H2,1-2H3/t24-,25-,26+,27+,29+/m1/s1
  • Key:TXHUMRBWIWWBGW-GVGNIZHQSA-N

十一酸雌二醇（estradiol undecylate）缩写EU或E2U，又称十一酸雌酮，曾在Delestrec（英语：Delestrec）和Progynon Depot 100等品牌名下销售，是一种雌激素药物，曾用于治疗男性摄护腺癌[10][11][12][13][1]。它还作为跨性别女性激素疗法的一种方式[14][15][16]。尽管十一酸雌二醇过去曾经使用，但目前已停产[12][17]。该药物通常摄入方式是每月一次的肌肉注射[1][18][13]。

十一酸雌二醇对男性的副作用可能包括乳房压痛、乳房发育、女性化、性功能障碍、不孕不育、液体滞留和心血管问题[18]。十一烷基雌二醇是一种雌激素，因此，是雌激素受体的激动剂，而雌激素受体是雌激素的生物靶标，如雌二醇[6][19][20]。它是一种雌激素酯，是体内雌二醇的一种非常持久[6]的前体药物[4]。正因为如此，它被认为是一种天然和生物相同的雌激素形式。注射十一酸雌二醇的持续时间约为1至4个月[8][9][7][21]。

十一酸雌二醇首次被描述是在1953年，并在1956年被引入医学应用[8][22][9][23]。它一直在2000年代后期之前被使用，然后停产。十一酸雌二醇曾在欧洲市场上销售，但似乎从未在美国上市[24][12][25]。多年来，它被用作治疗男性摄护腺癌的肌注雌激素，尽管使用频率不如聚磷酸雌二醇。有的跨性别女性会自行制作此种药物以实施女性化激素疗法。

医疗用途[编辑]

十一酸雌二醇曾被用作高剂量雌激素疗法的一种形式，用于治疗前列腺（俗称“高雌抗雄”），但后来在这个适应症上被新一代药物取代，这些新药物具有更少的不良效应（例如乳腺增生和心血管并发症），如GnRH类似物和非甾体抗雄激素[1][26]。它已在许多临床研究中用于评估这个目的[27][28][29][30][31]。它以每3到4周（或每月一次）100毫克的剂量通过肌肉注射用于这个适应症[18][32]。

十一酸雌二醇有抗雄激素类似的效果，曾被用于抑制性犯罪者的性欲[33]。对此适应症，它的剂量为每3到4周一次，肌肉注射50到100毫克[33]。

十一酸雌二醇还曾用于治疗女性的乳腺癌[34]。它也在更年期激素疗法中使用，例如用于缓解潮热和其他更年期症状[9]。与雌二醇戊酸酯、雌二醇环戊酸酯和苯甲酸雌二醇一起，十一酸雌二醇已被用作肌肉注射雌激素，用于跨性别女性的激素疗法[14][15][16]，剂量为每月100毫克至800毫克不等[15][16][14][35][36][37]。

可用形式[编辑]

十一酸雌二醇可作为肌肉注射的油溶液，一种规格是以100 mg/mL的药物浓度的安瓿瓶。[38][39]

禁忌症[编辑]

参见：雌二醇(药物)§禁忌症（英语：Estradiol (medication)#Contraindications）

十一酸雌二醇作为一种雌激素，禁忌症包括凝血问题、心血管疾病、肝脏疾病以及某些激素敏感性癌症，例如乳腺癌和子宫内膜癌等。[40][41][42][43]

副作用[编辑]

主条目：雌二醇(药物)§副作用（英语：Estradiol (medication)#Side effects）

十一酸雌二醇及其副作用曾在由美因茨大学大学泌尿科Jacobi及其同事主持的III期国际多中心随机对照试验中进行评估，用于治疗晚期前列腺癌[18][44][45][46][47][28][48]。该研究包括来自12个治疗中心的191名患者，这些患者接受了为期6个月的肌肉注射，其中96名患者每月接受100毫克的十一酸雌二醇，另有95名患者每周接受300毫克的醋酸环丙孕酮[44][46][47][28][48][49][50]。该研究的一个分支首次于1978年和1980年报告了Mainz大学中心的42名患者[51][18][28][48]。

这些患者年龄在51到84岁之间（平均68岁），排除了有预先存在心血管疾病的患者[13][18][52]。对于十一酸雌二醇组报告了相当高的心血管并发症发生率（76％；21/16总发生率），其中心血管发病率为67％（21/14），心血管死亡率为9.5％（21/2）[13][18][52]。该组中的心血管发病包括外周水肿和表层静脉炎（38％；21/8），冠心病（24％；21/5）和深静脉血栓形成（4.8％；21/1）[18][52]，而心血管死亡则包括心肌梗死（4.8％；21/1）和肺栓塞（4.8％；21/1）。

十一酸雌二醇组中的八例心血管并发症，包括两例死亡，被认为是“严重的”[52][53]。相反，在环丙烯酸乙酯对照组中未发生心血管毒性（0％；21/0）[13][18][52]。十一酸雌二醇的其他副作用还包括乳腺增生（100％；21/21）和勃起功能障碍（90％；21/19）[18]。在这相对较小的研究中，十一酸雌二醇的心血管并发症与高剂量的聚磷酸雌二醇和经皮雌二醇治疗前列腺癌的大规模和高质量的临床研究形成对比，这些研究中观察到最少或没有心血管有害性[54][55][56][57][58]。

药物过量[编辑]

参见：雌二醇(药物)§药物过量（英语：Estradiol (medication)#Overdose）

十一酸雌二醇曾在临床上以每月高达800至2400毫克的大剂量通过肌肉注射使用，分为每周两到三次注射[59][60][61][62][63]，每次注射100至200毫克。作为比较，有报告指出，单次100毫克肌肉注射的十一酸雌二醇可导致约500pg/mL的雌二醇水平[64]。雌激素过量的症状可能包括恶心、呕吐、腹胀、体重增加、水肿、乳房疼痛、阴道分泌物增加、腿沉和腿部抽筋[65]。这些副作用可以通过降低摄入剂量来减轻[65]。

互动[编辑]

药理[编辑]

药效学[编辑]

药代动力学[编辑]

化学性质[编辑]

历史[编辑]

社会与文化[编辑]

通用名[编辑]

雌二醇十一酸酯（Estradiol undecylate）是该药物的通用名称、国际非专利药品名称（INN）和美国药典通用名称（USAN）。[66][67][68][69] 有些出版物中也将其拼写为雌二醇十一酸酯，同时也被称为雌二醇十一酸酯。[70][66][67][68][69] 在德国，它有多种拼写，包括 estradiolundecylat、östradiolundecylat、östradiolundezylat、oestradiolundecylat、oestradiolundezylat 等。[71] 雌二醇十一酸酯还以其先前的开发代码名称 RS-1047 和 SQ-9993 而闻名。[66][67][68][69]

商品名[编辑]

雌二醇十一酸酯的主要品牌名称是 Progynon Depot 100。[66][67][68]除了 Progynon Depot 100 外，雌二醇十一酸酯还以其他品牌名称上市，包括 Delestrec、Depogin、Estrolent、Oestradiol D、Oestradiol-Retard Theramex 和 Primogyn Depot [0.1 mg/ml] 等。[66][67][68][72][73]

可用性[编辑]

雌二醇十一酸酯在欧洲（包括法国、德国、英国、摩纳哥、荷兰、瑞士）以及日本是可用的。[68][72][74][75][76] 然而，它已被停产，因此不再可获得。[77][78]


参考[编辑]

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