Testosterone undecanoate, an orally administered ester prodrug of the anabolic steroid of testosterone, acts as an effective testosterone replacement therapy[1]. Testosterone undecanoate demonstrates the capability to stabilize testosterone levels while creating azoospermia conditions in men[2]. Testosterone undecanoate serves as a treatment for hypogonadism and is being tested for male contraceptive use[2].
In vitro, Testosterone undecanoate has anti-proliferative activity[3]. Treatment of 200μg/ml testosterone undecanoate plus 0.1μg/ml anastrozole for 24-48 hours can inhibit the proliferation of MCF-7 cells, promote cell apoptosis, and cause a significant decrease in androgen receptor protein expression[3].
In vivo, Testosterone undecanoate can cause benign prostatic hyperplasia[4]. Subcutaneous injection of 125mg/kg Testosterone undecanoate every 2-3 weeks caused high serum levels of testosterone, dihydrotestosterone, and 5-alpha reductase in castrated male Wistar rats (12 week-age), accompanied by elevated prostate weight, prostate volume, and prostate index[4]. Intramuscular injection of 1000mg Testosterone undecanoate at 12-week intervals was well tolerated in male hypogonadism patients, resulting in a return of testosterone levels to the normal range (16.5±8.0nmol/L)[5]. Following intramuscular injection of Testosterone undecanoate (20mg/kg/week) in male adult rhesus monkeys for 60 days, massive germ cell apoptosis occurred in the testis, and the HSP70-2 mRNA and protein levels decreased significantly[6-7]. Intramuscular injection of Testosterone undecanoate (500mg/kg/45days) caused the improved locomotor activity, the enhanced preference to novel objects, spatial memory, and reversed anxiety and depression induced by AlCl3+D-galactose administration in male mice with Alzheimer's disease, along with the altered gene expression levels of Na/K ATPase isoforms in the hippocampus of the brain[8].
References:
[1]Zgair A, Dawood Y, Ibrahem S M, et al. Predicting intestinal and hepatic first-pass metabolism of orally administered testosterone undecanoate[J]. Applied Sciences, 2020, 10(20): 7283.
[2]Yu M, Cao X, Xu J, et al. Effects of testosterone undecanoate as a male contraceptive candidate on rat immunological features[J]. Immunopharmacology and immunotoxicology, 2003, 25(4): 627-643.
[3] Chen R, Cui J, Wang Q, et al. Antiproliferative effects of anastrozole on MCF‑7 human breast cancer cells in vitro are significantly enhanced by combined treatment with testosterone undecanoate[J]. Molecular Medicine Reports, 2015, 12(1): 769-775.
[4]An J, Kong H. Comparative application of testosterone undecanoate and/or testosterone propionate in induction of benign prostatic hyperplasia in Wistar rats[J]. PloS one, 2022, 17(5): e0268695.
[5]Schubert M, Minnemann T, Hubler D, et al. Intramuscular testosterone undecanoate: pharmacokinetic aspects of a novel testosterone formulation during long-term treatment of men with hypogonadism[J]. The Journal of Clinical Endocrinology & Metabolism, 2004, 89(11): 5429-5434.
[6]Zhou X C, Zhang Z H, Hu Z Y, et al. Expression of Hsp70–2 in rhesus monkey testis during germ cell apoptosis induced by testosterone undecanoate[J]. Contraception, 2002, 66(5): 377-382.
[7]Zhang Z H, Zhou X C, Wei P, et al. Expression of Bcl-2 and Bax in rhesus monkey testis during germ cell apoptosis induced by testosterone undecanoate[J]. Archives of andrology, 2003, 49(6): 439-447.
[8]Elfouly A, Awny M, Ibrahim M K, et al. Effects of Long-Acting Testosterone Undecanoate on Behavioral Parameters and Na+, K+-ATPase mRNA Expression in Mice with Alzheimers Disease[J]. Neurochemical Research, 2021, 46(9): 2238-2248.
Testosterone undecanoate是一种口服的合成代谢类固醇睾酮的酯前体药，可作为一种有效的睾酮替代疗法[1]。Testosterone undecanoate具有在造成男性无精子症的情况下稳定睾酮水平的能力[2]。Testosterone undecanoate被用作治疗性腺功能减退症，并被测试用于男性避孕[2]。
Testosterone undecanoate在体外具有抗增殖活性[3]。200μg/ml的Testosterone undecanoate联合0.1μg/ml阿那曲唑处理MCF-7细胞24-48h可抑制细胞增殖，促进细胞凋亡，并引起雄激素受体蛋白表达明显下降[3]。
Testosterone undecanoate在体内可引起良性前列腺增生[4]。12周龄雄性Wistar大鼠去势后，每2-3周皮下注射125mg/kg的Testosterone undecanoate，导致血清睾酮、双氢睾酮和5-α还原酶水平升高，并伴有前列腺重量、前列腺体积和前列腺指数升高[4]。男性性腺功能减退症患者每隔12周肌内注射1000mg的Testosterone undecanoate可使睾酮水平恢复至正常范围（16.5±8.0nmol/L）[5]。成年雄性恒河猴肌内注射Testosterone undecanoate（20mg/kg/周）60天后，睾丸出现大量生殖细胞凋亡，HSP70-2 的mRNA和蛋白水平显著下降[6-7]。肌内注射Testosterone undecanoate（500mg/kg/45天）改善了阿尔茨海默病雄性小鼠的自主活动，增强了对新事物的偏好和空间记忆，并逆转了由AlCl3+D-半乳糖诱导的焦虑和抑郁症状，同时改变了大脑海马Na/K ATP酶各异型基因的表达水平[8]。