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

Information source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Kallmann Syndrome; Idiopathic Hypogonadotropic Hypogonadism; GnRH Deficiency

Intervention: gonadotropin releasing hormone (GnRH) (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: William Crowley

Official(s) and/or principal investigator(s):
William F Crowley, Jr., MD, Principal Investigator, Affiliation: Massachusetts General Hospital

Overall contact:
Ravikumar Balasubramanian, MD, PhD, Phone: 617-726-8432, Email: rbalasubramanian@mgh.harvard.edu

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.

Clinical Details

Official title: The Effects of 7 Days of Exogenous Pulsatile GnRH Treatment on the Pituitary-Gonadal Axis in Hypogonadotropic Hypogonadal Subjects

Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

testosterone

LH

FSH

Inhibin B

free alpha subunit

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.

Eligibility

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Male.

Criteria:

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

Locations and Contacts

Ravikumar Balasubramanian, MD, PhD, Phone: 617-726-8432, Email: rbalasubramanian@mgh.harvard.edu

Massachusetts General Hospital, Boston, Massachusetts 02114-2696, United States; Recruiting
Ravikumar Balasubramanian, MD, PhD, Phone: 617-726-8432, Email: rbalasubramanian@mgh.harvard.edu
Nirav Patel, BA, Phone: 617-726-1896, Email: npatel34@mgh.harvard.edu
Paul A Boepple, MD, Sub-Investigator
Frances J Hayes, MD, Sub-Investigator
Nelly Pitteloud, MD, Sub-Investigator
Stephanie B Seminara, MD, Sub-Investigator

Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
Ravikumar Balasubramanian, MD, PhD, Phone: 617-726-8432, Email: rbalasubramanian@mgh.harvard.edu
Nirav Patel, BA, Phone: 617-726-1896, Email: npatel34@mgh.harvard.edu

Additional Information

Clinical research studies of the Reproductive Endocrine Unit at the Massachusetts General Hospital. Click here for more information about this study: Effects of Seven Days of Exogenous Pulsatile GnRH Treatment...

Related publications:

Belchetz PE, Plant TM, Nakai Y, Keogh EJ, Knobil E. Hypophysial responses to continuous and intermittent delivery of hypopthalamic gonadotropin-releasing hormone. Science. 1978 Nov 10;202(4368):631-3.

Seminara SB, Hayes FJ, Crowley WF Jr. Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations. Endocr Rev. 1998 Oct;19(5):521-39. Review.

Arimura A, Kastin AJ, Gonzalez-Barcena D, Siller J, Weaver RE, Schally AV. Disappearance of LH-releasing hormone in man as determined by radioimmunoassay. Clin Endocrinol (Oxf). 1974 Oct;3(4):421-5.

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Filicori M, Butler JP, Crowley WF Jr. Neuroendocrine regulation of the corpus luteum in the human. Evidence for pulsatile progesterone secretion. J Clin Invest. 1984 Jun;73(6):1638-47.

Narasimha Rao P, Moore PH Jr. Synthesis of new steroid haptens for radioimmunoassay. Part I. 15beta-Carboxyethylmercaptotestosterone-bovine serum albumin conjugate. Measurement of testosterone in male plasma without chromatography. Steroids. 1976 Jul;28(1):101-9.

Groome NP, Illingworth PJ, O'Brien M, Pai R, Rodger FE, Mather JP, McNeilly AS. Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab. 1996 Apr;81(4):1401-5.

Landy H, Schneyer AL, Whitcomb RW, Crowley WF Jr. Validation of highly specific and sensitive radioimmunoassays for lutropin, follitropin, and free alpha subunit in unextracted urine. Clin Chem. 1990 Feb;36(2):340-4.

Starting date: January 1999
Last updated: April 13, 2015

Page last updated: August 23, 2015

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