Follicle Stimulating Hormone (FSH) to Improve Testicular Development in Men With Hypogonadism - Full Text View

Sponsor:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00064987

Purpose

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.

Condition	Intervention	Phase
Hypogonadism Kallmann Syndrome	Procedure: Testicular biopsy Drug: gonadotropin releasing hormone (GnRH) Drug: follicle stimulating hormone (FSH)	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Role of FSH in Human Gonadal Development

Resource links provided by NLM:

Genetics Home Reference related topics: Kallmann syndrome persistent Müllerian duct syndrome

MedlinePlus related topics: Infertility

Drug Information available for: Gonadorelin Gonadorelin hydrochloride Follicle Stimulating Hormone LH-RH

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

LH [ Time Frame: weekly & monthly ] [ Designated as safety issue: No ]
FSH [ Time Frame: weekly & monthly ] [ Designated as safety issue: No ]
testosterone [ Time Frame: weekly & monthly ] [ Designated as safety issue: No ]
Inhibin B [ Time Frame: weekly & monthly ] [ Designated as safety issue: No ]
testicular size (volume) [ Time Frame: monthly ] [ Designated as safety issue: No ]
sperm count [ Time Frame: monthly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Fertility [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	April 2001
Estimated Study Completion Date:	July 2014
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Intervention Details:

Outpatient surgical procedure.

Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump titrated to reach normal serum testosterone levels)

75 IU subcutaneous injection daily for four months.

Other Name: Gonal-F

Detailed Description:

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 undergo an initial assessment that includes an overnight 12-hour frequent blood sampling study, testicular ultrasound, and testicular biopsy. Patients will be followed through monthly study visits with blood tests and seminal fluid analysis. Patients will also have serial testicular ultrasounds to measure testicular growth. Patients in Group 1 will also have a second frequent blood sampling to measure LH, FSH, and testosterone and to confirm the absence of LH pulses.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

no history of spontaneous puberty
clinical hypogonadism
infantile testes (< 3 ml)
no reproductive hormone therapy except testosterone
Complete absence of normal LH pulses during 12-hour baseline frequent blood sampling and serum testosterone < 100 ng/dl
Normal testing of the anterior pituitary gland
Negative MRI of the hypothalamic-pituitary area

Exclusion Criteria

Prior therapy with gonadotropins (FSH, hCG, or GnRH)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064987

Locations

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

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

Investigators

Principal Investigator:

William F Crowley, Jr., MD

Massachusetts General Hospital

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Pitteloud N, Hayes FJ, Dwyer A, Boepple PA, Lee H, Crowley WF Jr. Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2002 Sep;87(9):4128-36.

Pitteloud N, Hayes FJ, Boepple PA, DeCruz S, Seminara SB, MacLaughlin DT, Crowley WF Jr. The role of prior pubertal development, biochemical markers of testicular maturation, and genetics in elucidating the phenotypic heterogeneity of idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2002 Jan;87(1):152-60.

Hayes FJ, Pitteloud N, DeCruz S, Crowley WF Jr, Boepple PA. Importance of inhibin B in the regulation of FSH secretion in the human male. J Clin Endocrinol Metab. 2001 Nov;86(11):5541-6.

Kumar PA, Pitteloud N, Andrews PA, Dwyer A, Hayes F, Crowley WF Jr, Dym M. Testis morphology in patients with idiopathic hypogonadotropic hypogonadism. Hum Reprod. 2006 Apr;21(4):1033-40. Epub 2006 Jan 5.

Responsible Party:	William F. Crowley Jr., MD, MGH
ClinicalTrials.gov Identifier:	NCT00064987 History of Changes
Other Study ID Numbers:	U54HD028138-457
Study First Received:	July 16, 2003
Last Updated:	August 31, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Male reproduction hormones
Hypogonadotropic hypogonadism
FSH
LH
GnRH

Additional relevant MeSH terms:

Hypogonadism
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
Follicle Stimulating Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012