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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00493961
Recruitment Status : Active, not recruiting
First Posted : June 29, 2007
Last Update Posted : March 29, 2018
Information provided by (Responsible Party):
William F. Crowley, Jr., M.D., National Institute of Child Health and Human Development

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.

Condition or disease Intervention/treatment Phase
Kallmann Syndrome Idiopathic Hypogonadotropic Hypogonadism GnRH Deficiency Drug: gonadotropin releasing hormone (GnRH) Not Applicable

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effects of 7 Days of Exogenous Pulsatile GnRH Treatment on the Pituitary-Gonadal Axis in Hypogonadotropic Hypogonadal Subjects
Study Start Date : January 1999
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : May 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones
Drug Information available for: Gonadorelin
U.S. FDA Resources

Intervention Details:
    Drug: gonadotropin releasing hormone (GnRH)
    Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump)

Primary Outcome Measures :
  1. testosterone [ Time Frame: daily for 7 days ]
  2. LH [ Time Frame: frequent sampling for 2 hours ]
  3. FSH [ Time Frame: frequent sampling for 2 hours ]
  4. Inhibin B [ Time Frame: daily for 7 days ]
  5. free alpha subunit [ Time Frame: daily for 7 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00493961

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114-2696
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
William F. Crowley, Jr., M.D.
Principal Investigator: William F Crowley, Jr., MD Massachusetts General Hospital

Additional Information:
Publications of Results:
Other Publications:

Responsible Party: William F. Crowley, Jr., M.D., Professor, National Institute of Child Health and Human Development Identifier: NCT00493961     History of Changes
Other Study ID Numbers: U54HD028138-447
U54HD028138 ( U.S. NIH Grant/Contract )
First Posted: June 29, 2007    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018

Keywords provided by William F. Crowley, Jr., M.D., National Institute of Child Health and Human Development:
Kallmann Syndrome
Idiopathic Hypogonadotropic Hypogonadism
GnRH deficiency

Additional relevant MeSH terms:
Kallmann Syndrome
Gonadal Disorders
Endocrine System Diseases
46, XY Disorders of Sex Development
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs