摘要A multicenter,open-label,randomized,controlled superiority trial with 18 months of follow-up was conducted to investigate whether oral zinc supplementation could further promote spermatogenesis in males with isolated hypogonadotropic hypogonadism (IHH) receiving sequential purified urinary follicular-stimulating hormone/human chorionic gonadotropin (uFSH/hCG) replacement.Sixty-seven Chinese male IHH patients were recruited from the Departments of Endocrinology in eight tertiary hospitals and randomly allocated into the sequential uFSH/hCG group (Group A,n ＝ 34) or the sequential uFSH plus zinc supplementation group (Group B,n ＝ 33).In Group A,patients received sequential uFSH (75 U,three times a week every other 3 months) and hCG (2000 U,twice a week) treatments.In Group B,patients received oral zinc supplementation (40 mg day-1) in addition to the sequential uFSH/hCG treatment given to patients in Group A.The primary outcome was the proportion of patients with a sperm concentration ≥1.0 × 106 ml-1 during the 18 months.The comparison of efficacy between Groups A and B was analyzed.Nineteen of 34 (55.9％) patients receiving sequential uFSH/hCG and 20 of 33 (60.6％) patients receiving sequential uFSH/hCG plus zinc supplementation achieved sperm concentrations ≥1.0 x 106 ml-1 by intention to treat analyses.No differences between Group A and Group B were observed as far as the efficacy of inducing spermatogenesis (P ＝ 0.69).We concluded that the sequential uFSH/hCG plus zinc supplementation regimen had a similar efficacy to the sequential uFSH/hCG treatment alone.The additional improvement of 40 mg day-1 oral zinc supplementation on spermatogenesis and masculinization in male IHH patients is very subtle.