Data Sheet 1_Comparing the response of triple therapy and conventional treatment in male congenital hypogonadotropic hypogonadism: a randomized controlled trial.docx

BackgroundThis study investigated whether triple therapy with human chorionic gonadotropin (hCG), follicle-stimulating hormone(FSH) and testosterone(T) in congenital hypogonadotropic hypogonadism(CHH) promoted more timely virilization, aiding psychosocial development while reducing hCG requirements, offering a balanced approach to long-term management.
MethodsAn open-label randomized controlled trial (1:1:1) was conducted in adult males with CHH. Group A received triple therapy, Group B received combined hCG and FSH from the outset, and Group C received hCG monotherapy followed by combined FSH and hCG. Initial doses comprised hCG 2,000 IU twice weekly, FSH 75 IU thrice weekly and intramuscular testosterone(T) 100 mg every two weeks. Group A titrated hCG to achieve AMH of 7.4ng/ml; Groups B and C aimed for T normalization. Primary outcomes were hCG/FSH doses required for spermatogenesis induction and the time to spermatogenesis.
ResultsForty-five CHH males (mean age 25.8 ± 6.1years) were randomized. Spermatogenesis was achieved in 84.6% of group A participants compared with 69.2% and 75% in groups B and C, respectively(p=0.648). Median hCG dose at spermatogenesis was 7500IU/week in group A and 9000IU/week in groups B and C(p=0.016). The time to spermatogenesis was comparable (Groups A/B:12 months; Group C:15 months;p=0.345). Group A participants achieved an AMH of 3.5(2.31-5.38)ng/ml, comparable to the other groups(p=0.962). Predictors of spermatogenesis included USGmTV cut-off of 1.97ml (sensitivity-86.2%,specificity-62.5%), hCG dose of 9,000 IU/week (sensitivity-79.3%,specificity-87.5%) and an Inh B cut-off of 66.8 pg/ml(sensitivity-92.6%,specificity-100%).
ConclusionsTriple therapy provided a better quality of life without compromising spermatogenesis. The AMH and Inh B provided an effective means of monitoring.
Clinical trial registrationwww.ctri.nic.in, identifier CTRI/2022/05/042795.

背景：本研究旨在探讨针对先天性促性腺激素低下型性腺功能减退症（congenital hypogonadotropic hypogonadism, CHH）患者，采用绒毛膜促性腺激素（human chorionic gonadotropin, hCG）、卵泡刺激素（follicle-stimulating hormone, FSH）联合睾酮（testosterone, T）的三联疗法，能否更及时地促进男性化进程，助力患者社会心理发育，同时减少hCG用药剂量，为长期管理提供平衡方案。
方法：本研究针对成年男性CHH患者开展一项1:1:1开放标签随机对照试验。A组接受三联疗法，B组自初始阶段即联合使用hCG与FSH，C组先采用hCG单药治疗，后续联合FSH与hCG。初始给药方案为：hCG 2000IU，每周2次；FSH 75IU，每周3次；肌内注射睾酮100mg，每2周1次。A组调整hCG剂量以使抗缪勒管激素（anti-Müllerian hormone, AMH）达到7.4ng/ml；B组与C组则以睾酮水平恢复正常为目标。主要结局指标为诱导精子发生所需的hCG/FSH剂量，以及达到精子发生的时间。
结果：共45名男性CHH患者纳入随机分组，平均年龄25.8±6.1岁。A组患者精子发生成功率为84.6%，B组、C组分别为69.2%、75%（p=0.648）。达到精子发生时的hCG中位剂量：A组为7500IU/周，B、C组为9000IU/周（p=0.016）。各组达到精子发生的时间无显著差异（A/B组：12个月；C组：15个月；p=0.345）。A组患者AMH水平达3.5(2.31~5.38)ng/ml，与其他两组无显著差异（p=0.962）。精子发生的预测因素包括：超声测量睾丸容积阈值1.97ml（灵敏度86.2%，特异度62.5%）、hCG剂量9000IU/周（灵敏度79.3%，特异度87.5%）以及抑制素B（inhibin B, Inh B）阈值66.8pg/ml（灵敏度92.6%，特异度100%）。
结论：三联疗法可在不影响精子发生的同时改善患者生活质量，抗缪勒管激素（AMH）与抑制素B（Inh B）可作为有效的临床监测指标。
临床试验注册：www.ctri.nic.in，注册号CTRI/2022/05/042795。