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

Phase 1

Completed

• Conditions: Kallmann Syndrome; Idiopathic Hypogonadotropic Hypogonadism; GnRH Deficiency

• Registration Number: NCT00493961
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

Men with Idiopathic Hypogonadotropic Hypogonadism (IHH) lack a hormone called gonadotropin releasing hormone (GnRH). This hormone is important for starting puberty, maintaining testosterone levels, and fertility. The purpose of this study is to research the effects of treating IHH men with GnRH for 7 days.

Detailed Description

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.

Study Timeline

• Study Start: 1999-01
• Study First Submitted: 2007-06-28
• Study First Submitted QC: 2007-06-28
• Study First Posted: 2007-06-29
• Primary Completion: 2009-11-17
• Study Completion: 2009-11-17
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-29
• Last Update Posted: 2022-07-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 27

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
free alpha subunit	daily for 7 days
LH	frequent sampling for 2 hours
testosterone	daily for 7 days
FSH	frequent sampling for 2 hours
Inhibin B	daily for 7 days

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States