Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome

Study Overview
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Brief Summary
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To investigate the hormone response of hypothalamic-pituitary-gonad axis and spermatogenesis in male pituitary stalk interruption syndrome patients by pulsatile GnRH therapy.

Detailed Description
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To investigate the hormone response of hypothalamic-pituitary-gonad axis and spermatogenesis in male pituitary stalk interruption syndrome patients by pulsatile GnRH therapy. The hormonal response of the hypothalamic-pituitary-gonad axis was assessed after pulsatile GnRH replacement by measurement of serum T, LH and FSH. A standard seminal fluid analysis was performed in men who could produce an ejaculate.

Official Title
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Efficacy of Pulsatile GnRH Therapy on Male Patients With Pituitary Stalk Interruption Syndrome

Conditions
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Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: Gonadotropin-releasing Hormone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or over male patients; Absent or incomplete puberty development; Serum testosterone values below 3.47 nmol/L by low or normal serum LH and FSH concentrations. at least two or more pituitary hormone deficiencies Brain MRI showed absent and thin pituitary stalk, or pituitary hypoplasia and/or ectopic posterior pituitary. Exclusion Criteria: cryptorchidism history other causes of hypopituitarism or severe systemic disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>patients were administered with pulsatile gonadotropin-releasing hormone (GnRH )therapy for 12 months at an interval of 90 minutes.The GnRH dosage was initially 10ug per pulse and was progressively adjusted to maintain serum testosterone levels at 6.94-17.35 nmol/L. | Drug: Gonadotropin-releasing Hormone<br>* A regimen of pulsatile GnRH (Fengyuan pharmaceutical company, Anhui province, China) administered subcutaneous via a portable infusion pump (Weichuang Medical Science Company, Shanghai city, China) at a 90-minute interval. The GnRH dosage was initially 10ug per pulse and was progressively adjusted to maintain serum testosterone levels at 6.94-17.35 nmol/L ( 200-500 ng/dL).<br>* Other names: Gonadorelin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of serum Luteinizing Hormone(LH) value | Luteinizing hormone (LH) is measured using commercial kits by chemiluminescent method (ACS 180 Automatic Chemiluminescence System; Bayer). Reference range: 1.24-8.62 IU/L. Initial efficacy is evaluated based on the values of serum LH and serum total testosterone. If a subject's serum LH value below 1.5 IU/L and serum total testosterone value below 100 ng/dL at 3m post treatment, it is defined as failure to pulsatile GnRH treatment and continuous treatment is stopped. Otherwise, pulsatile GnRH treatment is continued. | Baseline and at 1m,3m, 6m, 9m and 12m post treatment. | 
| Change of serum Follicle-Stimulating Hormone (FSH) value | Follicle-stimulating hormone (FSH) are measured using commercial kits by chemiluminescent method (ACS 180 Automatic Chemiluminescence System; Bayer). Reference range: 1.27-19.26 IU/L. | Baseline and at 1m,3m, 6m, 9m and 12m post treatment. | 
| Change of serum total testosterone value | Total testosterone levels are measured using commercial kits by chemiluminescent method (ACS 180 Automatic Chemiluminescence System; Bayer). Reference range: 175-781 ng/dL.Initial efficacy is evaluated based on the values of serum LH and serum totaltestosterone. If a subject's serum LH value below 1.5 IU/L and serum total testosterone value below 100 ng/dL at 3m post treatment, it is defined as failure to pulsatile GnRH treatment and continuous treatment is stopped. Otherwise, pulsatile GnRH treatment is continued. | Baseline and at 1m,3m, 6m, 9m and 12m post treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of testicular volume | Testicular volumes are measured using Prader orchidometer. Prader orchidometer is a standard method to measure testicular volume. The normal range of testicular volume of each side in normal adult men is 15-25ml. | Baseline and at 1m,3m, 6m, 9m and 12m post treatment | 
| Change of sperm counts by routine semen analysis | if a subject can produce an ejaculate, semen samples are collected by masturbation and analyzed according to the standard World Health Organization method. | Baseline and at 3m, 6m, 9m and 12m post treatment | 
| the rate of impregnating subject's wife | For subjects who have sex partners, pregnancies are documented according to subjects' reports after treatment. | at 3m, 6m, 9m and 12m post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypopituitarism, pituitary stalk interruption syndrome, pulsatile GnRH therapy, hypogonadotropic hypogonadism