Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa; GONAL-f®): long-term treatment in azoospermic men with hypogonadotropic hypogonadism

ObjectiveTo demonstrate the efficacy and safety of follitropin alfa administered with hCG on spermatogenesis in adult male hypogonadotropic hypogonadism (HH) patients.DesignPhase III, multicenter, open-label, noncomparative.SettingSeven US medical centers.Patient(s)A total of 36 adult males with severe HH.Intervention(s)A total of 1,000 U hCG on alternate days for 3 to 6 months, with dose adjustments after 2 months, if necessary, to normalize T levels, followed by follitropin alfa 150 U and hCG on the same alternate days for 18 months, with dose adjustments as necessary.Main Outcome Measure(s)Proportion of patients with sperm density ≥1.5 × 106/mL. Pubertal advancement and long-term safety and tolerability were also evaluated.Result(s)In total, 22 of 29 patients (75.9%) who received ≥1 dose of follitropin alfa and 20 of 25 patients (80%) who completed 18 months of hCG + follitropin alfa treatments achieved a sperm concentration ≥1.5 × 106/mL. A sperm concentration >20 × 106/mL was achieved by 8 of 29 men (27.5%). Median sperm concentration at 18 months was 5.2 × 106/mL. Pubertal development continued during the study, and testis volumes increased. Five clinical pregnancies were achieved. Acne (52% of patients) was the most common side effect, and gynecomastia was reported in 10% of patients.Conclusion(s)Long-term treatment of azoospermic HH men using follitropin alfa and hCG is effective for stimulating spermatogenesis and is well-tolerated.