Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa; GONAL-f®): long-term treatment in azoospermic men with hypogonadotropic hypogonadism
Received 26 March 2008; received in revised form 23 June 2008; accepted 15 July 2008. published online 20 October 2008.
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 ≥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.
Reprint requests: Jim Brentzel, B.S., EMD Serono, Inc., One Technology Place, Rockland, MA 02370 (FAX: 781-681-2901).
A.M.M. has received consultation fees and research funding from a number of pharmaceutical companies including GSK and Solvay Pharmaceuticals. P.J.S. has nothing to disclose. S.B. has received a research grant from Solvay Pharmaceuticals and study materials supplied by Auxilium. K.M. is the Senior Deputy Editor of a scientific journal. T.W. has nothing to disclose. S.W. has nothing to disclose. D.S. has nothing to disclose. J.B. is currently employed by EMD Serono, Inc. L.O. was previously employed by EMD Serono, Inc., an affiliate of Merck KGaA, Darmstadt, Germany.
Supported by EMD Serono, Inc., Rockland, Massachusetts, USA.
∗ Current address: Department of Endocrinology, Nutrition, and Diabetes, Boston, Medical Center, Boston, MA. Study patients were enrolled at Harbor-UCLA Medical Center, Torrance, CA.
† Current address: Division of Endocrinology, Metabolism and Diabetes, University of Louisville, KY.
ABSTRACT