Studying the Effects of 7 Days of Gonadotropin Releasing Hormone (GnRH) Treatment in Men With Hypogonadism

Despite variability in the triggers, timing, and pace of sexual maturity between species, all
species utilize the final pathway of hypothalamic secretion of gonadotropin releasing hormone
(GnRH) to initiate and maintain the reproductive axis. Thus, GnRH is required for
reproductive competence in the human. The classic studies from the 1970s clearly demonstrate
that pulsatile release of GnRH from the hypothalamus is a prerequisite for physiologic
gonadotrope function. Absence, decreased frequency or decreased amplitude of pulsatile GnRH
release results in the clinical syndrome of hypogonadotropic hypogonadism (HH). The
phenotypic expression of GnRH deficiency in the human demonstrates considerable
heterogeneity. Defining the physiology of GnRH is critical to understanding the clinical
heterogeneity of isolated GnRH deficiency and its comparison to other conditions resulting in
hypogonadotropic hypogonadism (HH). The overall goal of this protocol is to investigate the
neuroendocrine control of reproduction and specifically the physiology and pathophysiology of
GnRH secretion and action in the human male.

Subjects will be selected from a group of adult men (18-65 years)based on the demonstration
of a low testosterone level (<100 ng/dL) in association with low or inappropriately normal
gonadotropin levels. All patients will undergo an initial assessment that includes an
overnight 12-hour frequent blood sampling study to determine their degree of endogenous GnRH
secretion. Following the overnight evaluation, subjects will have daily outpatient visits for
7 consecutive days when they will receive a GnRH bolus followed by 2hrs of blood sampling.

Inclusion Criteria:

- Diagnosis of idiopathic hypogonadotropic hypogonadism (IHH) or Kallmann syndrome
(KS)Adult male 18-65 years of age

- Serum testosterone <100 ng/dL

Exclusion Criteria:

- No specific exclusion criteria