Meikle A W, Matthias D, Hoffman A R
Department of Medicine, Division of Endocrinology, University of Utah School of Medicine, 615 Arapeen Drive, Suite 100, Salt Lake City, UT 84108, USA.
BJU Int. 2004 Apr;93(6):789-95. doi: 10.1111/j.1464-410X.2003.04750.x.
To determine the regimen that would most effectively maintain serum testosterone concentrations in treated hypogonadal men within the normal reference range of 3-11.4 microg/L.
Eighteen men aged 24-69 years with either primary or secondary hypogonadism participated in and 16 completed a randomized, six-treatment regimen, three-period (phase), three-way matrix-type crossover study. A 1% and 2% testosterone gel (CP601, Cellegy Pharmaceuticals, Inc., San Francisco, USA) was administered either once or twice daily transdermally at different body sites to determine optimal dosing, application sites, and its pharmacokinetics and tolerability in hypogonadal men. Treatments A-F included 1 g of 1% and 2% gel that was equivalent to 10 or 20 mg of testosterone, applied once or twice daily to the skin of either the thigh or the upper arm. Six men also participated in a study of 3 g of 2% gel that was equivalent to 60 mg of testosterone applied once daily, half on each thigh. Pharmacokinetic variables were calculated for testosterone for each man in each treatment period and the results analysed by anova.
In general the higher dose regimens produced higher serum concentrations of testosterone; the 3 g/2% dose was most successful in maintaining serum testosterone within the normal reference range. The average testosterone concentration (C(avg)) was 6.52 microg/L and all men had a C(avg) of > 3.0 microg/L. The prediction of all men achieving a C(avg) of > 3.0 microg/L was 96%. The mean minimum concentration (C(min)) was 3.83 microg/L and half the patients had a C(min) of > 3.0 microg/L. Most men had serum testosterone levels within the normal reference range throughout the 24 h, and the treatment was well tolerated.
The 3 g/2% dose applied to the skin daily resulted in serum testosterone in the normal reference range in most hypogonadal men. Dose adjustments to either a lower or higher dose should shift serum testosterone concentration to the desired range in those who do not achieve this range with this dose.
确定能最有效地将接受治疗的性腺功能减退男性的血清睾酮浓度维持在3 - 11.4微克/升正常参考范围内的治疗方案。
18名年龄在24 - 69岁之间的原发性或继发性性腺功能减退男性参与了研究，16人完成了一项随机、六治疗方案、三阶段（期）、三向矩阵式交叉研究。将1%和2%的睾酮凝胶（CP601，美国旧金山Cellegy制药公司）在不同身体部位每日经皮给药一次或两次，以确定最佳给药剂量、给药部位及其在性腺功能减退男性中的药代动力学和耐受性。治疗A - F包括1克1%和2%的凝胶，分别相当于10毫克或20毫克睾酮，每日一次或两次涂抹于大腿或上臂皮肤。6名男性还参与了一项研究，使用3克2%的凝胶，相当于60毫克睾酮，每日一次，分别涂抹于双侧大腿。计算每个男性在每个治疗期的睾酮药代动力学变量，并通过方差分析对结果进行分析。
总体而言，较高剂量方案产生的血清睾酮浓度更高；3克/2%剂量在将血清睾酮维持在正常参考范围内最为成功。平均睾酮浓度（C(avg)）为6.52微克/升，所有男性的C(avg)均> 3.0微克/升。所有男性C(avg)> 3.0微克/升的预测概率为96%。平均最低浓度（C(min)）为3.83微克/升，半数患者的C(min)> 3.0微克/升。大多数男性在24小时内血清睾酮水平处于正常参考范围内，且该治疗耐受性良好。
每日将3克/2%剂量涂抹于皮肤可使大多数性腺功能减退男性的血清睾酮处于正常参考范围内。对于使用该剂量未达到此范围的患者，调整剂量至更低或更高剂量应能使血清睾酮浓度达到理想范围。
