Abstract：
OBJECTIVE: Human choriogonadotrophin (hCG) treatment of gonadotrophin-deficient infertile men uses hCG of urinary (uhCG) or recombinant (rhCG) origin, but these treatments have not been compared nor are there studies defining rhCG dosing in men.
METHODS: hCG products were studied in randomized cross-over single-dose studies of standard (Study 1, 1500 IU and 62.5 µg, respectively) or high (Study 2, 5000 IU and 250 µg) dose and a multi-dose population pharmacology study of hCG use.
METHODS: Eight (Study 1) and seven (Study 2) volunteers in cross-over and 52 gonadotrophin-deficient men in the multi-dose study MEASUREMENTS: In cross-over studies, serum testosterone (T), dihydrotestosterone (DHT) and estradiol by liquid chromatography-mass spectrometry (LCMS) and serum hCG, LH, FSH, SHBG and T (observational study) by immunoassays.
RESULTS: After standard and high-dose injection, serum hCG and testosterone responses had similar timing and peak concentrations except for a mildly lower early (<48 h) serum testosterone with uhCG. In the multi-dosing study, both hCGs had similar pharmacokinetics (pooled half-life 5.8 days, p < .001), while serum testosterone concentrations were stable after injection and did not differ between hCG products. Bench testing verified that 20% of pens from 4/10 individuals were used inappropriately.
CONCLUSIONS: Although hCG pharmacokinetics are not formally bioequivalent, the similar pharmacodynamic effects on serum testosterone indicate that at the doses tested both hCGs provide comparable clinical effects. The starting dose of rhCG for treating gonadotrophin-deficient men should be 62.5 µg (6 clicks) of the rhCG pen.
METHODS: hCG products were studied in randomized cross-over single-dose studies of standard (Study 1, 1500 IU and 62.5 µg, respectively) or high (Study 2, 5000 IU and 250 µg) dose and a multi-dose population pharmacology study of hCG use.
METHODS: Eight (Study 1) and seven (Study 2) volunteers in cross-over and 52 gonadotrophin-deficient men in the multi-dose study MEASUREMENTS: In cross-over studies, serum testosterone (T), dihydrotestosterone (DHT) and estradiol by liquid chromatography-mass spectrometry (LCMS) and serum hCG, LH, FSH, SHBG and T (observational study) by immunoassays.
RESULTS: After standard and high-dose injection, serum hCG and testosterone responses had similar timing and peak concentrations except for a mildly lower early (<48 h) serum testosterone with uhCG. In the multi-dosing study, both hCGs had similar pharmacokinetics (pooled half-life 5.8 days, p < .001), while serum testosterone concentrations were stable after injection and did not differ between hCG products. Bench testing verified that 20% of pens from 4/10 individuals were used inappropriately.
CONCLUSIONS: Although hCG pharmacokinetics are not formally bioequivalent, the similar pharmacodynamic effects on serum testosterone indicate that at the doses tested both hCGs provide comparable clinical effects. The starting dose of rhCG for treating gonadotrophin-deficient men should be 62.5 µg (6 clicks) of the rhCG pen.
摘要：
目的：人类绒毛膜促性腺激素（hCG）治疗缺乏促性腺激素的不育男性使用尿（uhCG）或重组（rhCG）来源的hCG，但是这些治疗方法尚未进行比较，也没有研究定义rhCG在男性中的剂量。
方法：hCG产品在标准的随机交叉单剂量研究中进行了研究（研究1，1500IU和62.5µg，分别）或高（研究2，5000IU和250µg）剂量和hCG使用的多剂量人群药理学研究。
方法：8名（研究1）和7名（研究2）交叉志愿者和52名促性腺激素缺乏的男性在多剂量研究中测量：在交叉研究中，血清睾酮(T),双氢睾酮(DHT)和雌二醇通过液相色谱-质谱(LCMS)和血清hCG,LH,FSH,通过免疫测定的SHBG和T(观察性研究)。
结果：在标准和高剂量注射后，血清hCG和睾酮反应具有相似的时间和峰值浓度,除了早期(<48h)血清睾酮与uhCG轻度降低.在多剂量研究中，两种hCG具有相似的药代动力学（合并半衰期5.8天，p<.001),而注射后血清睾酮浓度稳定，不同hCG产品之间没有差异。台架测试验证了来自4/10个体的20％的笔被不适当地使用。
结论：尽管hCG的药代动力学在形式上不是生物等效的，对血清睾酮的相似药效学效应表明,在所测试的剂量下,两种hCG提供了相当的临床效果.用于治疗促性腺激素缺乏的男性的rhCG的起始剂量应为rhCG笔的62.5µg（6次点击）。
方法：hCG产品在标准的随机交叉单剂量研究中进行了研究（研究1，1500IU和62.5µg，分别）或高（研究2，5000IU和250µg）剂量和hCG使用的多剂量人群药理学研究。
方法：8名（研究1）和7名（研究2）交叉志愿者和52名促性腺激素缺乏的男性在多剂量研究中测量：在交叉研究中，血清睾酮(T),双氢睾酮(DHT)和雌二醇通过液相色谱-质谱(LCMS)和血清hCG,LH,FSH,通过免疫测定的SHBG和T(观察性研究)。
结果：在标准和高剂量注射后，血清hCG和睾酮反应具有相似的时间和峰值浓度,除了早期(<48h)血清睾酮与uhCG轻度降低.在多剂量研究中，两种hCG具有相似的药代动力学（合并半衰期5.8天，p<.001),而注射后血清睾酮浓度稳定，不同hCG产品之间没有差异。台架测试验证了来自4/10个体的20％的笔被不适当地使用。
结论：尽管hCG的药代动力学在形式上不是生物等效的，对血清睾酮的相似药效学效应表明,在所测试的剂量下,两种hCG提供了相当的临床效果.用于治疗促性腺激素缺乏的男性的rhCG的起始剂量应为rhCG笔的62.5µg（6次点击）。
