Objective: To demonstrate the efficacy and safety of follitropin alfa administered with hCG on spermatogenesis in adult male hypogonadotropic hypogonadism (HH) patients.
Design: Phase III, multicenter, open-label, noncomparative.
Setting: Seven 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 > or =1.5 x 10(6)/mL. Pubertal advancement and long-term safety and tolerability were also evaluated.
Result(s): In total, 22 of 29 patients (75.9%) who received > or =1 dose of follitropin alfa and 20 of 25 patients (80%) who completed 18 months of hCG + follitropin alfa treatments achieved a sperm concentration > or =1.5 x 10(6)/mL. A sperm concentration >20 x 10(6)/mL was achieved by 8 of 29 men (27.5%). Median sperm concentration at 18 months was 5.2 x 10(6)/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.