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

Fertil Steril. 2009 Sep;92(3):979-990. doi: 10.1016/j.fertnstert.2008.07.1742. Epub 2008 Oct 18.


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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Azoospermia / drug therapy*
  • Azoospermia / pathology
  • Chorionic Gonadotropin / pharmacology
  • Chorionic Gonadotropin / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Follicle Stimulating Hormone, Human / adverse effects
  • Follicle Stimulating Hormone, Human / pharmacology*
  • Follicle Stimulating Hormone, Human / therapeutic use*
  • Glycoprotein Hormones, alpha Subunit / adverse effects
  • Glycoprotein Hormones, alpha Subunit / pharmacology*
  • Glycoprotein Hormones, alpha Subunit / therapeutic use*
  • Humans
  • Hypogonadism / drug therapy*
  • Hypogonadism / pathology
  • Male
  • Middle Aged
  • Organ Size
  • Sperm Motility / drug effects
  • Spermatogenesis / drug effects*
  • Spermatozoa / drug effects
  • Testis / drug effects
  • Testis / pathology
  • Testosterone / blood
  • Treatment Outcome
  • United States
  • Young Adult


  • Chorionic Gonadotropin
  • Follicle Stimulating Hormone, Human
  • Glycoprotein Hormones, alpha Subunit
  • Testosterone