Gooren Louis J G, Bunck Mathijs C M
Department of Endocrinology, Section of Andrology, VU University Medical Center, Amsterdam, The Netherlands.
Drugs. 2004;64(17):1861-91. doi: 10.2165/00003495-200464170-00002.
The major goal of androgen substitution is to replace testosterone at levels as close to physiological levels as is possible. For some androgen-dependent functions testosterone is a pro-hormone, peripherally converted to 5alpha-dihydrotestosterone (DHT) and 17beta-estradiol (E2), of which the levels preferably should be within normal physiological ranges. Furthermore, androgens should have a good safety profile without adverse effects on the prostate, serum lipids, liver or respiratory function, and they must be convenient to use and patient-friendly, with a relative independence from medical services. Natural testosterone is viewed as the best androgen for substitution in hypogonadal men. The reason behind the selection is that testosterone can be converted to DHT and E2, thus developing the full spectrum of testosterone activities in long-term substitution. The mainstays of testosterone substitution are parenteral testosterone esters (testosterone enantate and testosterone cipionate) administered every 2-3 weeks. A major disadvantage is the strongly fluctuating levels of plasma testosterone, which are not in the physiological range at least 50% of the time. Also, the generated plasma E2 is usually supraphysiological. A major improvement is parenteral testosterone undecanoate producing normal plasma levels of testosterone for 12 weeks, with normal plasma levels of DHT and E2 also. Subcutaneous testosterone implants provide the patient, depending on the dose of implants, with normal plasma testosterone for 3-6 months. However, their use is not widespread. Oral testosterone undecanoate dissolved in castor oil bypasses the liver via its lymphatic absorption. At a dosage of 80 mg twice daily, plasma testosterone levels are largely in the normal range, but plasma DHT tends to be elevated. For two decades transdermal testosterone preparations have been available and have an attractive pharmacokinetic profile. Scrotal testosterone patches generate supraphysiological plasma DHT levels, which is not the case with the nonscrotal testosterone patches. Transdermal testosterone gel produces fewer skin irritations than the patches and offers greater flexibility in dosage. Oromucosal testosterone preparations have recently become available. Testosterone replacement is usually of long duration and so patient compliance is of utmost importance. Therefore, the patient must be involved in the selection of type of testosterone preparation. Administration of testosterone to young individuals has almost no adverse effects. With increasing age the risk of adverse effects on the prostate, the cardiovascular system and erythropoiesis increases. Consequently, short-acting testosterone preparations are better suited for aging androgen-deficient men.
雄激素替代疗法的主要目标是尽可能使睾酮水平接近生理水平。对于一些依赖雄激素的功能而言，睾酮是一种前体激素，可在周围组织中转化为5α-二氢睾酮（DHT）和17β-雌二醇（E2），其水平最好处于正常生理范围内。此外，雄激素应具有良好的安全性，对前列腺、血脂、肝脏或呼吸功能无不良影响，并且必须使用方便且对患者友好，相对独立于医疗服务。天然睾酮被视为性腺功能减退男性替代治疗的最佳雄激素。选择它的原因是睾酮可以转化为DHT和E2，从而在长期替代治疗中发挥睾酮的全部活性。睾酮替代治疗的主要方式是每2 - 3周注射一次睾酮酯（庚酸睾酮和环戊丙酸睾酮）。一个主要缺点是血浆睾酮水平波动很大，至少50%的时间不在生理范围内。此外，所产生的血浆E2通常高于生理水平。一个重大改进是注射用十一酸睾酮可使血浆睾酮水平在12周内保持正常，同时DHT和E2的血浆水平也正常。皮下植入睾酮制剂根据植入剂量不同，可为患者提供3 - 6个月的正常血浆睾酮水平。然而，其应用并不广泛。口服溶于蓖麻油的十一酸睾酮通过淋巴吸收绕过肝脏。每日两次服用80毫克的剂量时，血浆睾酮水平基本处于正常范围，但血浆DHT往往会升高。二十年来，经皮睾酮制剂已经问世，并且具有吸引人的药代动力学特征。阴囊睾酮贴片会使血浆DHT水平高于生理水平，而非阴囊睾酮贴片则不会。经皮睾酮凝胶引起的皮肤刺激比贴片少，并且在剂量方面具有更大的灵活性。口腔黏膜睾酮制剂最近也已上市。睾酮替代治疗通常持续时间较长，因此患者的依从性至关重要。所以，患者必须参与睾酮制剂类型的选择。对年轻人使用睾酮几乎没有不良影响。随着年龄的增长，对前列腺、心血管系统和红细胞生成产生不良影响的风险会增加。因此，短效睾酮制剂更适合老年雄激素缺乏的男性。
