Bhasin S, Swerdloff R S, Steiner B, Peterson M A, Meridores T, Galmirini M, Pandian M R, Goldberg R, Berman N
Harbor-University of California-Los Angeles Medical Center, Torrance 90509.
J Clin Endocrinol Metab. 1992 Jan;74(1):75-83. doi: 10.1210/jcem.74.1.1727832.
Limitations of presently available testosterone esters (enanthate and cypionate) include the fluctuating serum testosterone levels and the need for relatively frequent injections (every 10-21 days). These limitations of testosterone esters have prompted the development of more physiological and longer acting systems for androgen delivery. This paper reports pharmacokinetic and pharmacodynamic data with a second generation long-acting testosterone microcapsule formulation in hypogonadal men. This was a single dose, open label, nonrandomized study. Ten hypogonadal men with primary (n = 6) or secondary (n = 4) hypogonadism, otherwise in good health, received 630 mg microencapsulated testosterone in dextran solution (IM) on day 1. Serum total and free testosterone; LH; FSH; dihydrotesterone; estradiol; sex hormone-binding globulin; total cholesterol; high, low, and very low density lipoprotein cholesterol; triglycerides; and apoprotein-AII and -B were measured on multiple occasions during the 2-week control period and the 16-week treatment period. In addition, on days 0, 1, 28, 56, and 84, subjects were hospitalized for detailed hormone analyses over the 24-h period. Serum total and free testosterone levels rose quickly into the midnormal range and stayed uniformly in the eugonadal range for about 70-77 days, after which serum testosterone levels declined gradually into the hypogonadal range. Testosterone release from the microcapsule formulation over the first 10 weeks approximated zero order kinetics. Serum dihydrotestosterone levels rose into the normal range, and testosterone to dihydrotestosterone ratios remained in the physiological range. Serum estradiol levels rose and stayed in the midnormal male range. Serum sex hormone-binding globulin levels decreased significantly during treatment. Serum LH and FSH levels also significantly decreased in the six hypergonadotropic men. Total cholesterol low and very low density lipoprotein cholesterol and triglyceride levels did not change, but plasma high density lipoprotein cholesterol levels decreased significantly during treatment. These data indicate that testosterone microcapsule formulation provides uniform eugonadal levels of testosterone for about 10 weeks. The long duration and zero order kinetics make it an attractive alternative to existing methods of androgen replacement.
目前可用的睾酮酯（庚酸睾酮和环戊丙酸睾酮）存在一些局限性，包括血清睾酮水平波动以及需要相对频繁地注射（每10 - 21天一次）。睾酮酯的这些局限性促使人们开发更具生理性且作用时间更长的雄激素递送系统。本文报告了第二代长效睾酮微胶囊制剂在性腺功能减退男性中的药代动力学和药效学数据。这是一项单剂量、开放标签、非随机研究。10名原发性（n = 6）或继发性（n = 4）性腺功能减退且身体健康的男性在第1天接受了630毫克微囊化睾酮的右旋糖酐溶液（肌肉注射）。在为期2周的对照期和16周的治疗期内多次测量血清总睾酮和游离睾酮、促黄体生成素（LH）、促卵泡生成素（FSH）、双氢睾酮、雌二醇、性激素结合球蛋白、总胆固醇、高密度、低密度和极低密度脂蛋白胆固醇、甘油三酯以及载脂蛋白 - AII和 - B。此外，在第0、1、28
、56和84天，受试者住院进行为期24小时的详细激素分析。血清总睾酮和游离睾酮水平迅速升至正常范围中部，并在正常性腺功能范围内均匀维持约70 - 77天，此后血清睾酮水平逐渐下降至性腺功能减退范围。微胶囊制剂在最初10周内的睾酮释放近似零级动力学。血清双氢睾酮水平升至正常范围，睾酮与双氢睾酮的比值保持在生理范围内。血清雌二醇水平升高并维持在男性正常范围中部。治疗期间血清性激素结合球蛋白水平显著下降。6名性腺功能亢进男性的血清LH和FSH水平也显著降低。总胆固醇、低密度和极低密度脂蛋白胆固醇以及甘油三酯水平未发生变化，但治疗期间血浆高密度脂蛋白胆固醇水平显著下降。这些数据表明，睾酮微胶囊制剂可在约10周内提供均匀的正常性腺功能水平的睾酮。其作用时间长和零级动力学使其成为现有雄激素替代方法的一个有吸引力的替代方案。
