聚磷酸雌二醇

**聚磷酸雌二醇**
	上图：聚磷酸雌二醇的键线式，下图：雌二醇磷酸酯（英语：estradiol phosphate）（聚磷酸雌二醇的单体）的球棒模型
临床资料
商品名（英语：Drug nomenclature）	Estradurin, Estradurine
其他名称	PEP; Estradiol phosphate polymer; Estradiol 17β-phosphate polymer; Estradiol polymer with phosphoric acid; Leo-114
AHFS/Drugs.com	国际药品名称
怀孕分级	禁忌;
给药途径	肌肉注射
药物类别（英语：Drug class）	雌激素药物、雌激素酯（英语：Estrogen ester）
ATC码	L02AA02 (WHO) ;
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	肌肉注射: 高
血浆蛋白结合率	雌二醇：~98%（和albumin及SHBG）
药物代谢	主要是靠肝脏，少部分会透过肾、生殖腺及肌肉（透过磷酸酶）
代谢产物	雌激素药物、磷酸及雌激素的代谢产物
生物半衰期	PEP: 70 days (10 weeks); Estradiol: 1–2 hours
排泄途径	尿）（依生物转化作用）
识别信息
	IUPAC命名法 Estra-1,3,5(10)-triene-3,17β-diol, polymer with phosphoric acid; ;
CAS号	28014-46-2
PubChem SID	51091766;
DrugBank	DB09369 ;
ChemSpider	None;
UNII	P14877CDX2;
KEGG	D07434 ;
ChEMBL	ChEMBL1201477 ;
化学信息
化学式	(C18H23O4P)n; (n = variable; n = 13)
摩尔质量	聚合物: 不固定; 重复单元（英语：Repeat unit）: 334.347 g/mol
熔点	195至202 °C（383至396 °F）

聚磷酸雌二醇（Polyestradiol phosphate），简称PEP，药品名称Estradurin，是用来治疗男性前列腺癌的雌激素（英语：Estrogen (medication)）药品^[1]^[9]^[2]^[10]。也可以用来作为治疗女性的乳癌、是治疗低雌激素症（英语：hypoestrogenism）及更年期症状的激素替代疗法药物之一，也是给跨性别女性的女性化贺尔蒙治疗^[1]^[11]，以每4个星期一次肌肉注射的方式给药^[1]^[2]^[12]。

参考文献[编辑]

^ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 Archived copy. [2018-01-01]. （原始内容存档于2018-01-02）.
^ ^2.0 ^2.1 ^2.2 Mikkola A, Ruutu M, Aro J, Rannikko S, Salo J. The role of parenteral polyestradiol phosphate in the treatment of advanced prostatic cancer on the threshold of the new millennium. Ann Chir Gynaecol. 1999, 88 (1): 18–21. ISSN 0355-9521. PMID 10230677. Orchiectomy and estrogens have been used for over 50 years in the treatment of advanced prostatic cancer. Although orchiectomy is a simple procedure, it may cause psychological stress. Oral estrogen therapy is as effective as orchiectomy in terms of cancer inhibitory effect, but its acceptance as primary hormonal treatment is overshadowed by an increased risk of cardiovascular complications. Parenteral estrogen, polyestradiol phosphate (PEP), is effective, but also associated with cardiovascular complications, although to a lesser extent. During the last 20 years, well tolerated luteinizing hormone releasing hormone (LHRH) analogues have been replacing orchiectomy and estrogens. Efforts have been made to increase the efficacy of the treatment by adding antiandrogens to LHRH analogues and also to orchiectomy (combined androgen blockade, CAB). However, the efficacy of LHRH analogues and CAB has not proved to be superior to that of simple orchiectomy and, moreover, they are expensive treatment modalities. Orchiectomy and LHRH analogues are associated with negative effects on bone mass and may cause osteoporosis, whereas PEP treatment has an opposite effect. Parenteral polyestradiol phosphate is still a cheap potential treatment for advanced prostatic cancer, but further studies should be conducted to establish its future role, e.g. combining acetylsalicylic acid to prevent cardiovascular complications.
^ Stanczyk, Frank Z.; Archer, David F.; Bhavnani, Bhagu R. Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment. Contraception. 2013, 87 (6): 706–727. ISSN 0010-7824. PMID 23375353. doi:10.1016/j.contraception.2012.12.011.
^ Tommaso Falcone; William W. Hurd. Clinical Reproductive Medicine and Surgery. Elsevier Health Sciences. 2007: 22,362,388 [2021-01-26]. ISBN 978-0-323-03309-1. （原始内容存档于2021-04-15）.
^ Michael Oettel; Ekkehard Schillinger. Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. 6 December 2012: 261,544 [2021-01-26]. ISBN 978-3-642-60107-1. （原始内容存档于2021-03-07）. Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens.
^ Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration (PDF). Climacteric. 2005,. 8 Suppl 1: 3–63 [2021-01-26]. PMID 16112947. S2CID 24616324. doi:10.1080/13697130500148875. （原始内容 (PDF)存档于2016-08-22）.
^ Stege R, Gunnarsson PO, Johansson CJ, Olsson P, Pousette A, Carlström K. Pharmacokinetics and testosterone suppression of a single dose of polyestradiol phosphate (Estradurin) in prostatic cancer patients. Prostate. May 1996, 28 (5): 307–10. PMID 8610057. doi:10.1002/(SICI)1097-0045(199605)28:5<307::AID-PROS6>3.0.CO;2-8.
^ Düsterberg B, Nishino Y. Pharmacokinetic and pharmacological features of oestradiol valerate. Maturitas. 1982, 4 (4): 315–24. PMID 7169965. doi:10.1016/0378-5122(82)90064-0.
^ Stege R, Carlström K, Hedlund PO, Pousette A, von Schoultz B, Henriksson P. Intramuskuläres Depotöstrogen (Estradurin) in der Behandlung von Patienten mit Prostatakarzinom. Historische Aspekte, Wirkungsmechanismus, Resultate und aktueller klinischer Stand [Intramuscular depot estrogens (Estradurin) in treatment of patients with prostate carcinoma. Historical aspects, mechanism of action, results and current clinical status]. Urologe A. September 1995, 34 (5): 398–403. ISSN 0340-2592. PMID 7483157 （德语）. More than 50 years ago, orally given estrogen was already used in the treatment of prostate cancer. Due to cardiovascular side-effects with a high morbidity of 25%, this treatment has not become standard. Recent investigations show that parenteral application reduces the risk of cardiovascular side-effects, because it avoids the first passage through the liver with high concentrations of estrogen which normally occur after oral application. Therefore, an increased synthesis of so-called "steroid-sensitive" liver proteins, such as coagulation factors (especially factor VII) can be avoided. This newer parenteral estrogen application shows encouraging results of a cheap and effective hormonal therapy with a low rate of side-effects in patients with prostate cancer.
^ Mikkola, A; Aro, J; Rannikko, S; Ruutu, M; Finnprostate, Group. Ten-year survival and cardiovascular mortality in patients with advanced prostate cancer primarily treated by intramuscular polyestradiol phosphate or orchiectomy. Prostate. March 2007, 67 (4): 447–55. PMID 17219379. S2CID 20549248. doi:10.1002/pros.20547.
^ Urdl, W. Behandlungsgrundsätze bei Transsexualität [Therapeutic principles in transsexualism]. Gynäkologische Endokrinologie. 2009, 7 (3): 153–160. ISSN 1610-2894. S2CID 8001811. doi:10.1007/s10304-009-0314-9 （德语）.
^ Steinbach T, Wurm FR. Poly(phosphoester)s: A New Platform for Degradable Polymers. Angew. Chem. Int. Ed. Engl. 2015, 54 (21): 6098–108. PMID 25951459. doi:10.1002/anie.201500147.

[Pharmanovia-Estradurin-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 Archived copy. [2018-01-01]. （原始内容存档于2018-01-02）.

[pmid10230677-2] 2.0 ^2.1 ^2.2 Mikkola A, Ruutu M, Aro J, Rannikko S, Salo J. The role of parenteral polyestradiol phosphate in the treatment of advanced prostatic cancer on the threshold of the new millennium. Ann Chir Gynaecol. 1999, 88 (1): 18–21. ISSN 0355-9521. PMID 10230677. Orchiectomy and estrogens have been used for over 50 years in the treatment of advanced prostatic cancer. Although orchiectomy is a simple procedure, it may cause psychological stress. Oral estrogen therapy is as effective as orchiectomy in terms of cancer inhibitory effect, but its acceptance as primary hormonal treatment is overshadowed by an increased risk of cardiovascular complications. Parenteral estrogen, polyestradiol phosphate (PEP), is effective, but also associated with cardiovascular complications, although to a lesser extent. During the last 20 years, well tolerated luteinizing hormone releasing hormone (LHRH) analogues have been replacing orchiectomy and estrogens. Efforts have been made to increase the efficacy of the treatment by adding antiandrogens to LHRH analogues and also to orchiectomy (combined androgen blockade, CAB). However, the efficacy of LHRH analogues and CAB has not proved to be superior to that of simple orchiectomy and, moreover, they are expensive treatment modalities. Orchiectomy and LHRH analogues are associated with negative effects on bone mass and may cause osteoporosis, whereas PEP treatment has an opposite effect. Parenteral polyestradiol phosphate is still a cheap potential treatment for advanced prostatic cancer, but further studies should be conducted to establish its future role, e.g. combining acetylsalicylic acid to prevent cardiovascular complications.

[pmid23375353-3] Stanczyk, Frank Z.; Archer, David F.; Bhavnani, Bhagu R. Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment. Contraception. 2013, 87 (6): 706–727. ISSN 0010-7824. PMID 23375353. doi:10.1016/j.contraception.2012.12.011.

[FalconeHurd2007-4] Tommaso Falcone; William W. Hurd. Clinical Reproductive Medicine and Surgery. Elsevier Health Sciences. 2007: 22,362,388 [2021-01-26]. ISBN 978-0-323-03309-1. （原始内容存档于2021-04-15）.

[OettelSchillinger2012-5] Michael Oettel; Ekkehard Schillinger. Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. 6 December 2012: 261,544 [2021-01-26]. ISBN 978-3-642-60107-1. （原始内容存档于2021-03-07）. Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens.

[pmid16112947-6] Kuhl H. Pharmacology of estrogens and progestogens: influence of different routes of administration (PDF). Climacteric. 2005,. 8 Suppl 1: 3–63 [2021-01-26]. PMID 16112947. S2CID 24616324. doi:10.1080/13697130500148875. （原始内容 (PDF)存档于2016-08-22）.

[pmid8610057-7] Stege R, Gunnarsson PO, Johansson CJ, Olsson P, Pousette A, Carlström K. Pharmacokinetics and testosterone suppression of a single dose of polyestradiol phosphate (Estradurin) in prostatic cancer patients. Prostate. May 1996, 28 (5): 307–10. PMID 8610057. doi:10.1002/(SICI)1097-0045(199605)28:5<307::AID-PROS6>3.0.CO;2-8.

[pmid7169965-8] Düsterberg B, Nishino Y. Pharmacokinetic and pharmacological features of oestradiol valerate. Maturitas. 1982, 4 (4): 315–24. PMID 7169965. doi:10.1016/0378-5122(82)90064-0.

[pmid7483157-9] Stege R, Carlström K, Hedlund PO, Pousette A, von Schoultz B, Henriksson P. Intramuskuläres Depotöstrogen (Estradurin) in der Behandlung von Patienten mit Prostatakarzinom. Historische Aspekte, Wirkungsmechanismus, Resultate und aktueller klinischer Stand [Intramuscular depot estrogens (Estradurin) in treatment of patients with prostate carcinoma. Historical aspects, mechanism of action, results and current clinical status]. Urologe A. September 1995, 34 (5): 398–403. ISSN 0340-2592. PMID 7483157 （德语）. More than 50 years ago, orally given estrogen was already used in the treatment of prostate cancer. Due to cardiovascular side-effects with a high morbidity of 25%, this treatment has not become standard. Recent investigations show that parenteral application reduces the risk of cardiovascular side-effects, because it avoids the first passage through the liver with high concentrations of estrogen which normally occur after oral application. Therefore, an increased synthesis of so-called "steroid-sensitive" liver proteins, such as coagulation factors (especially factor VII) can be avoided. This newer parenteral estrogen application shows encouraging results of a cheap and effective hormonal therapy with a low rate of side-effects in patients with prostate cancer.

[pmid17219379-10] Mikkola, A; Aro, J; Rannikko, S; Ruutu, M; Finnprostate, Group. Ten-year survival and cardiovascular mortality in patients with advanced prostate cancer primarily treated by intramuscular polyestradiol phosphate or orchiectomy. Prostate. March 2007, 67 (4): 447–55. PMID 17219379. S2CID 20549248. doi:10.1002/pros.20547.

[Urdl2009-11] Urdl, W. Behandlungsgrundsätze bei Transsexualität [Therapeutic principles in transsexualism]. Gynäkologische Endokrinologie. 2009, 7 (3): 153–160. ISSN 1610-2894. S2CID 8001811. doi:10.1007/s10304-009-0314-9 （德语）.

[pmid25951459-12] Steinbach T, Wurm FR. Poly(phosphoester)s: A New Platform for Degradable Polymers. Angew. Chem. Int. Ed. Engl. 2015, 54 (21): 6098–108. PMID 25951459. doi:10.1002/anie.201500147.

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