Adult-onset idiopathic hypogonadotropic hypogonadism — A treatable form of male infertility: Nachtigall L.B.; Boepple P.A.; Pralong F.P.; Crowley W.F. Jr. USA New Engl J Med 1997 336/6 (410–415)

Abstract

Background Men with isolated gonadotropinreleasing 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 GnRHreplacement 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. (N Engl J Med 1997;336:410-5.) ©1997, Massachusetts Medical Society.