Adult-onset idiopathic hypogonadotropic hypogonadism--a treatable form of male infertility

N Engl J Med. 1997 Feb 6;336(6):410-5. doi: 10.1056/NEJM199702063360604.


Background: Men with isolated gonadotropin-releasing hormone (GnRH) deficiency typically present with an absence of pubertal development. We describe an adult-onset form of idiopathic hypogonadotropic hypogonadism that develops after puberty.

Methods: We studied 10 men (age, 27 to 57 years) with normal sexual maturation, idiopathic infertility, sexual dysfunction, low serum testosterone concentrations, and apulsatile secretion of luteinizing hormone on frequent blood sampling. All the men had otherwise normal anterior pituitary hormone secretion and sellar anatomy. We compared the results of semen analyses and measurements of testicular volume, serum testosterone, inhibin B, and gonadotropins in these men with the results in 24 men with classic GnRH deficiency before and during GnRH-replacement therapy and in 29 normal men of similar age.

Results: Serum gonadotropin concentrations in the men with adult-onset GnRH deficiency were similar before and during pulsatile GnRH administration to those in the men with classic GnRH deficiency. However, as compared with men with classic GnRH deficiency, men with adult-onset hypogonadotropic hypogonadism had larger mean (+/-SD) testicular volumes (18+/-5 vs. 3+/-2 ml, P<0.001), serum testosterone concentrations (78+/-34 vs. 49+/-20 ng per deciliter [2.7+/-1.2 vs. 1.7+/-0.7 nmol per liter], P=0.004), and serum inhibin B concentrations (119+/-52 vs. 60+/-21 pg per milliliter, P<0.001). Treatment with GnRH reversed the hypogonadism and restored fertility in each of the five men who received long-term therapy.

Conclusions: The recognition of adult-onset hypogonadotropic hypogonadism in men as a distinct disorder expands the spectrum of GnRH deficiency and identifies a treatable form of male infertility.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age of Onset
  • Erectile Dysfunction / etiology
  • Gonadotropin-Releasing Hormone / blood
  • Gonadotropin-Releasing Hormone / deficiency*
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Gonadotropins, Pituitary / blood
  • Humans
  • Hypogonadism* / blood
  • Hypogonadism* / complications
  • Hypogonadism* / drug therapy
  • Infertility, Male / drug therapy
  • Infertility, Male / etiology*
  • Inhibins / blood
  • Libido
  • Male
  • Middle Aged
  • Reference Values
  • Testis / anatomy & histology
  • Testosterone / blood


  • Gonadotropins, Pituitary
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Inhibins