Clinical Trial: Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Role of FSH in Human Gonadal Development

Brief Summary: Men with idiopathic hypogonadotropic hypogonadism (IHH, Kallmann Syndrome) may have small testicular size, low testosterone levels, no history of puberty, and infertility. These men lack a hormone called gonadotropin releasing hormone (GnRH) that stimulates the development and maturation of the testes. This study will investigate the impact of hormonal treatments on men with IHH. The goal of hormonal therapy is to maximize the potential fertility in these individuals.

Detailed Summary:

Though steroid output of the testes is minimal during childhood, important changes take place that impact spermatogenic potential. Specifically, the number of Sertoli cells increases until testosterone secretion rises during puberty. In animal models, the proliferation of Sertoli cells appears to be regulated by follicle stimulating hormone (FSH) even though FSH levels in childhood are relatively low. At puberty, the number of Sertoli cells becomes fixed; however, the existing cell population then undergoes functional maturation. This switch from proliferation to maturation of Sertoli cells appears to result from rising levels of intratesticular testosterone.

FSH deficiency during testicular development results in decreased numbers of Sertoli cells, even if physiologic hormonal replacement therapy is introduced in adolescence or adulthood. The number of mature Sertoli cells appears to correlate with testicular size, sperm count, and future fertility. An improved understanding of the specific roles of FSH, luteinizing hormone (LH), and testosterone in testicular development may have direct clinical applications in the treatment of male infertility. This study will define the role of FSH in stimulating Sertoli cell proliferation in the human male.

Patients in this study will be randomized to receive either FSH and GnRH (Group 1) or GnRH alone (Group 2). Patients in Group 1 will receive subcutaneous FSH injections daily, titrated to achieve a FSH level of 4-8 IU/L, for 4 months. Patients will then receive GnRH therapy for 18 months. GnRH will be administered via a portable infusion pump at 2-hour intervals to stimulate endogenous LH secretion. Patients in Group 2 will receive the same regimen of exogenous GnRH for 18 months without prior FSH administration.

All patients will u
Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Current Primary Outcome:

  • LH [ Time Frame: weekly & monthly ]
  • FSH [ Time Frame: weekly & monthly ]
  • testosterone [ Time Frame: weekly & monthly ]
  • Inhibin B [ Time Frame: weekly & monthly ]
  • testicular size (volume) [ Time Frame: monthly ]
  • sperm count [ Time Frame: monthly ]


Original Primary Outcome:

Current Secondary Outcome: Fertility [ Time Frame: 24 months ]

Original Secondary Outcome:

Information By: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Dates:
Date Received: July 16, 2003
Date Started: April 2001
Date Completion:
Last Updated: March 29, 2017
Last Verified: March 2017