Clinical Trial: Examination of Idiopathic Hypogonadotropic Hypogonadism (IHH)and Kallmann Syndrome (KS)
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Role of Gonadotropin Pulsations in the Reversal of Hypogonadotropic Hypogonadism
Brief Summary:
The purpose of the study is to examine how Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) affect reproductive hormones. These disorders are caused by a defect in Gonadotropin Releasing Hormone (GnRH) secretion. GnRH is a hormone released by a small gland in the brain called the hypothalamus. When GnRH is released, it signals another gland in the brain, the pituitary, to secrete the reproductive hormones that influence testosterone levels and sperm production.
This study involves a detailed evaluation and 8-24 hours stay at the hospital.
In this study, males ages 16 and older with IHH have a detailed evaluation which involves an overnight study at the hospital. Some men (18 years and older) may continue on to receive treatment with pulsatile GnRH. This treatment replaces the hormone which is absent in IHH and results in normalized testosterone and typically is effective in developing fertility.
Detailed Summary:
The specific aims of this study are:
- To identify men and women with hypogonadotropic hypogonadism and to define the spectrum of abnormalities in GnRH secretion in these patients.
- To study the physiology and control of the reproductive system in the human male and female.
- To determine the relationship between glucose metabolism and testosterone levels in men with hypogonadotropic hypogonadism.
- To characterize the neuroendocrine and metabolic phenotype of subjects with IHH and use this information to make genotype-phenotype correlations.
Despite variability in the triggers, timing, and pace of sexual maturity between species, all species utilize the final pathway of hypothalamic secretion of GnRH to initiate and maintain the reproductive axis. Thus, GnRH is required for reproductive competence in the human. The classic studies of Knobil and his colleagues in the 1970s clearly demonstrated that pulsatile release of GnRH from the hypothalamus is a prerequisite for physiologic gonadotrope function, with continuous stimulation resulting in a paradoxical decrease in gonadotrope responsiveness.
Absence, decreased frequency or decreased amplitude of pulsatile GnRH release results in the clinical syndrome of hypogonadotropic hypogonadism (HH). Deficient GnRH secretion may occur in isolation (idiopathic hypogonadotropic hypogonadism [IHH]), in association with anosmia (Kallmann syndrome [KS]) or as a result of a variety of structural and functional lesions of the hypothalamic-pituitary axis. The phenotypic expression of GnRH deficiency in the human demonstrates considerable heterogeneity, suggesting that patients with IHH and KS may represent
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Current Primary Outcome: endogenous LH secretion pattern [ Time Frame: 8 to 24 hours ]
Original Primary Outcome:
- Assess reproductive hormones on a weekly basis for 2 months.
- After the first 2 months of treatment, hormones will be assessed on a monthly basis.
- After testosterone levels are maintained at >300 ng/dL semen samples will be collected on a monthly basis to assess sperm production and fertility.
Current Secondary Outcome:
- testicular volume [ Time Frame: up to 2 years ]
- sperm count [ Time Frame: up to 2 years ]
Original Secondary Outcome:
Information By: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Dates:
Date Received: October 25, 2006
Date Started: April 1989
Date Completion: March 2018
Last Updated: January 17, 2017
Last Verified: January 2017
