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

July 5, 2017 updated by: William Crowley, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Role of FSH in Human Gonadal Development

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Group 1 (FSH)
Patients in Group 1 will receive subcutaneous follicle stimulating hormone (FSH) injections daily, titrated to achieve a FSH level of 4-8 IU/L, for 4 months. Patients will then receive gonadotropin releasing hormone (GnRH) therapy for 18 months. GnRH will be administered via a portable infusion pump at 2-hour intervals to stimulate endogenous LH secretion.
Procedure: Testicular biopsy
Outpatient surgical procedure.
Drug: gonadotropin releasing hormone (GnRH)
Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump titrated to reach normal serum testosterone levels)
Drug: follicle stimulating hormone (FSH)
75 IU subcutaneous injection daily for four months.
Other Names:
  • Gonal-F
ACTIVE_COMPARATOR: Group 2 (GnRH)
Patients in Group 2 will receive gonadotropin releasing hormone (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 not receive prior FSH administration.
Procedure: Testicular biopsy
Outpatient surgical procedure.
Drug: gonadotropin releasing hormone (GnRH)
Pulsatile GnRH (25 ng/kg per bolus every two hours via microinfusion pump titrated to reach normal serum testosterone levels)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LH
Time Frame: month 4 of GnRH treatment
Average Luteinizing Hormone levels after treatment.
month 4 of GnRH treatment
FSH
Time Frame: month 4 of GnRH treatment
Average Follicle Stimulating Hormone levels after treatment.
month 4 of GnRH treatment
Testosterone
Time Frame: month 4 of GnRH treatment
Average Testosterone levels after treatment.
month 4 of GnRH treatment
Inhibin B
Time Frame: month 4 of GnRH treatment
Average Inhibin B Levels after treatment.
month 4 of GnRH treatment
Testicular Size (Volume)
Time Frame: at baseline and month 4 of GnRH treatment
Average testicular volume after treatment.
at baseline and month 4 of GnRH treatment
Sperm Count
Time Frame: month 4 of GnRH treatment
Average sperm count after treatment.
month 4 of GnRH treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fertility
Time Frame: 24 months
Participants actively seeking to conceive.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2001

Primary Completion (ACTUAL)

October 1, 2012

Study Completion (ACTUAL)

October 1, 2012

Study Registration Dates

First Submitted

July 16, 2003

First Submitted That Met QC Criteria

July 16, 2003

First Posted (ESTIMATE)

July 17, 2003

Study Record Updates

Last Update Posted (ACTUAL)

July 7, 2017

Last Update Submitted That Met QC Criteria

July 5, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • U54HD028138-457
  • U54HD028138 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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