简介
十一酸睾酮为雄激素类药，为睾酮的十一酸酯，是睾酮的衍生物。可促进男性生长，男性第二性征和睾丸、副性腺结构的发育，促进蛋白质合成，使其减少分解，增强免疫功能，促进骨骼生长，促进红细胞生成，反馈性抑制促性腺激素分泌，抑制雌激素分泌[1-2]。十一酸睾酮的常用剂型为胶囊剂、丸剂、注射剂。为激素药。用于治疗原发性或继发性睾丸功能减退；男孩体质性青春期延迟；乳腺癌转移的姑息性治疗；再生障碍性贫血的辅助治疗；中老年部分性雄激素缺乏综合征[3-4]。其结构式如图1所示。
图1十一酸睾酮的结构式。
应用
十一酸睾酮用于治疗原发性或继发性睾丸功能减退；男孩体质性青春期延迟；乳腺癌转移的姑息性治疗；还可以用于男性原发性或继发性性腺功能低下的睾酮补充疗法，例如睾丸切除后；无睾症；垂体功能低下；内分泌性阳萎；由于精子生成障碍所引起的不育症；男性更年期症状，例如性欲减退，脑力和体力下降等[5-7]。此外，十一酸睾酮用于男子性腺功能低下症的睾酮替代疗法，如睾丸切除以后、类无睾症、垂体功能低下、内分泌性阳萎、男子更年期症状（性欲、脑力及体力减退等）、某些因生精功能失调而致的不育症以及再生障碍性贫血等[8-10]。
不良反应
十一酸睾酮作为雄激素治疗可能引起的不良反应如下：良性肿瘤、恶性肿瘤和非定性肿瘤（包括囊肿和息肉）：良性前列腺增生、前列腺癌。血液和淋巴系统疾患：红细胞增多症。代谢和营养紊乱：液体和盐潴留[11]。精神紊乱：抑郁、紧张感、情绪困扰、性欲增强、性欲减退。胃肠道紊乱：恶心、腹泻、腹部不适、腹痛。肝胆病症：淤胆型黄疸。皮肤和皮下组织疾患：瘙痒。肌（与）骨骼及结缔组织疾患：肌痛、骨骺早闭。血管疾患：高血压。肾和泌尿疾患：泌尿疾病[12]。生殖系统和乳腺疾患：男子乳房女性化、少精、无精子、阴茎持续勃起症、勃起频率增加、加速性成熟、阴茎增大。肝功能异常、血清前列腺特异性抗原（PSA）升高、血红蛋白升高、红细胞压积升高、血脂异常。
药代动力学
与睾酮不同，十一酸睾酮口服后具有活性是因为其一部分与乳糜微粒结合，被吸收并释放进入体循环淋巴液。在药物吸收过程中，少量十一酸睾酮代谢为同样具有活性的5α-十一酸双氢睾酮[13]。吸收后，残留的药物成分在肠壁和肝脏内代谢成无活性的生物转化产物。吸收进入淋巴液的酯类物质经水解，在外周循环中转化成雌二醇。之后，这些游离类固醇向靶器官发挥雄激素活性。在稳态条件下，单次给予本品80-160mg，4－5小时后血浆睾酮水平达到峰值，约为40nmol/l[14]。血浆睾酮水平可在服药后维持8－12小时。消除过程与天然睾酮相同，都是通过葡萄糖醛酸反应完成的。终产物主要经肾脏排泄，少部分经粪便排出。
毒理作用
小鼠皮下注射十一酸睾酮3.7g/kg（大鼠有效量的270倍），14天内未发现死亡或异常反应。大鼠肌内注射十一酸睾酮每天每公斤42mg，连续6个月，未见明显的肝肾功能改变或其他损害。
药物相互作用
十一酸睾酮与环孢素合用，环孢素毒性增强，引发肾脏损害、胆汁淤积、感觉异常等不良反应，应避免合用。十一酸睾酮与肾上腺皮质激素合用，可加重水肿。十一酸睾酮与口服抗凝药合用，出血的危险性增加[15]。十一酸睾酮与巴比妥类合用，可使本药代谢加快，疗效降低。十一酸睾酮与当归合用，抑制本药代谢，增加其雄激素效应和不良反应发生率。糖尿病患者应用本药，能够降低血糖，故应减少胰岛素的用量十一酸睾酮与紫杉醇合用，可抑制紫杉醇的代谢，导致毒性增强[16-17]。
参考文献
[1] J.A. Adam, A.W. Pastuszak, M.B. Christensen, R. Spencer, A. Sandberg, J.M. Hotaling, L.I. Lipshultz, Occurrence of pulmonary oil microembolism (POME) with intramuscular testosterone undecanoate injection: literature review, Int. J. Impotence Res. (2022) Ahead of Print.
[2] J. An, H. Kong, Comparative application of testosterone undecanoate and/or testosterone propionate in induction of benign prostatic hyperplasia in Wistar rats, PLoS One 17(5) (2022) e0268695.
[3] A. DelConte, K. Papangkorn, K. Kim, B.J. Bruno, N. Chidambaram, M. Khera, I. Goldstein, T.S. Kohler, M. Miner, A.S. Dobs, M.V. Patel, A new oral testosterone (TLANDO) treatment regimen without dose titration requirement for male hypogonadism, Andrology 10(4) (2022) 669-676.
[4] O. Dhingra, J.S. Bernstein, S.Y. Shah, Preferred oral testosterone undecanoate therapy to achieve testosterone replacement treatment, Marius Pharmaceuticals LLC, USA . 2022, p. 28pp.
[5] A. Giwercman, K.B. Sahlin, I.P. Parada, K. Pawlowski, C. Fehninger, Y.L. Giwercman, I. Leijonhufvud, R. Appelqvist, G. Marko-Varga, A. Sanchez, J. Malm, Novel protein markers of androgen activity in humans: proteomic study of plasma from young chemically castrated men, eLife 11 (2022) e74638.
[6] D.J. Handelsman, R. Desai, A.J. Conway, N. Shankara-Narayana, B.G.A. Stuckey, W.J. Inder, M. Grossmann, B.B. Yeap, D. Jesudason, L.P. Ly, K. Bracken, G.A. Wittert, Recovery of male reproductive endocrine function after ceasing prolonged testosterone undecanoate injections, Eur. J. Endocrinol. 186(3) (2022) 307-318.
[7] S. Honig, M. Gittelman, J. Kaminetsky, C. Wang, J.K. Amory, N. Rohowsky, R.E. Dudley, B. Woun Seo, J. Newmark, R. Swerdloff, Two-Year Analysis of a New Oral Testosterone Undecanoate (TU) Formulation in Hypogonadal Men: Efficacy, Impact on Psychosexual Function, and Safety, J. Sex. Med. (2022) Ahead of Print.
[8] M.I. Kolind, L.L. Christensen, P. Caserotti, M.S. Andersen, D. Glintborg, Muscle function following testosterone replacement in men on opioid therapy for chronic non-cancer pain: A randomized controlled trial, Andrology 10(3) (2022) 551-559.
[9] T. Langer, O. Salamin, R. Nicoli, S. Grabherr, T. Kuuranne, A. Musenga, A comprehensive UHPLC-MS/MS method for the analysis of endogenous and exogenous steroids in serum for anti-doping purposes, Drug Test. Anal. (2022) Ahead of Print.
[10] B.J. Nolan, J. Proietto, P. Sumithran, Single-center real-life experience with testosterone treatment in adult men with Prader-Willi syndrome, Am. J. Med. Genet., Part A 188(9) (2022) 2637-2641.
[11] U. Ozkuvanci, M.I. Donmez, M.Z. Temiz, B. Cetin, C. Kuecuekgergin, V. Olgac, O. Ziylan, S. Seckin, T. Oktar, Effects of systemic androgens on late-stage urethral wound healing: An animal study, Andrology 10(4) (2022) 767-774.
[12] A. Van Hove, D. Janagam, G. Fieldson, Biodegradable polymer delivery system for extended delivery of testosterone, Tolmar International Limited, Ire. . 2022, p. 77pp.
[13] A.N. Varanoske, M.N. Harris, C. Hebert, E.E. Howard, N.M. Johannsen, S.B. Heymsfield, F.L. Greenway, L.M. Margolis, H.R. Lieberman, R.A. Beyl, D.D. Church, A.A. Ferrando, S.M. Pasiakos, J.C. Rood, Testosterone undecanoate administration prevents declines in fat-free mass but not physical performance during simulated multi-stressor military operations, J. Appl. Physiol. 133(2) (2022) 426-442.
[14] Y. Yang, Effect of Huiyao Shibao Decoction Combined with Testosterone Undecanoate on Serum Sex Hormone Levels in Middle-aged and Elderly Male Patients with Partial Androgen Deficiency Syndrome, Yaopin Pingjia 18(7) (2021) 64-66.
[15] A. Yassin, F. Saad, M. Alwani, O.M. Aboumarzouk, R.M. Al-Zoubi, J. Nettleship, D. Kelly, A. Al-Ansari, The effects of long-term testosterone treatment on endocrine parameters in hypogonadal men: 12-year data from a prospective controlled registry study, Aging Male 25(1) (2022) 185-191.
[16] S. Zelleroth, E. Nylander, E. Kjellgren, A. Groenbladh, M. Hallberg, Nandrolone decanoate and testosterone undecanoate differently affect stress hormones, neurotransmitter systems, and general activity in the male rat, Behav. Brain Res. 432 (2022) 113971.
[17] M. Zitzmann, J.F. Cremers, C. Krallmann, S. Kliesch, The HEAT-Registry (HEmatopoietic Affection by Testosterone): comparison of a transdermal gel vs long-acting intramuscular testosterone undecanoate in hypogonadal men, Aging Male 25(1) (2022) 134-144.