Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism

Study Overview
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Brief Summary
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Idiopathic hypogonadotropic hypogonadism (IHH) is the most common disorders of sex development (DSD).Therapy for IHH includes hormone replacement therapy, gonadotropin therapy and pulsed infusion of gonadotropin releasing hormone (GnRH).In the present study, we compared the different efficacy and safety of pulsatile GnRH pump therapy with combination gonadotropin therapy on fertility and sexual development in male patients with IHH.

Detailed Description
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Idiopathic hypogonadotropic hypogonadism (IHH) is the most common disorders of sex development (DSD).Therapy for IHH includes hormone replacement therapy, gonadotropin therapy and pulsed infusion of gonadotropin releasing hormone (GnRH).In the present study, we compared the different efficacy and safety of pulsatile GnRH pump therapy with combination gonadotropin therapy on fertility and sexual development in male patients with IHH. The primary endpoint was the achievement of pregnancy in female partner. Secondary endpoints were time to actual attainment of various sperm thresholds: sperm concentration>0*10^6/ml , >1.0 *10^6/ml and >15 *10^6/ml, respectively. The clinical and laboratory characteristics including testicular and prostatic volume, Tanner stage for pubic hair and genital, serum hormone levels [especially serum testosterone,luteinizing hormone (LH) , and Follicle-Stimulating Hormone (FSH) levels], sperm concentration per ejaculate, and adverse events at baseline and at the end of treatment were also evaluated.

Official Title
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Study on the Efficacy and Safety of Pulsatile Gonadotropin Releasing Hormone Pump Treatment in Patients With Idiopathic Hypogonadotropic Hypogonadism

Conditions
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Idiopathic Hypogonadotropic Hypogonadism

Intervention / Treatment
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* Drug: Pulsatile Gonadotropin Releasing Hormone
* Drug: Human chorionic gonadotropin
* Drug: Urinary Follicle-Stimulating Hormone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 16 yr Diagnosed as idiopathic hypogonadotropic hypogonadism with clinical signs or symptoms of hypogonadism Hypogonadal serum testosterone levels (<166ng/dl) in the presence of low or normal gonadotropins Normal levels of other anterior pituitary hormones Normal MRI scans of the hypothalamo-pituitary region Had discontinued any prior treatment (testosterone or gonadotropin therapy) for at least three months before enrollment Exclusion Criteria: With any significant medical condition (including malignant disease), laboratory abnormality, or psychiatric disorders that will prevent the subject from participating in the study Congenital hypopituitarism Any medical or surgical conditions possibly affecting the experiment result Any clinically significant allergic diseases or allergic to the study drugs Recently drug or alcohol abuse(>35unit/week,1unit=8 g alcohol@1 standard drink@250ml beer@140ml wine@25ml strong alcohol drink like whiskey.)

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pulsatile Gonadotropin Releasing Hormone<br>Pulsatile Gonadotropin Releasing Hormone: subjects in the GnRH group initiated a regimen of pulsatile GnRH administered subcutaneously via a portable infusion pump for 18 months. | Drug: Pulsatile Gonadotropin Releasing Hormone<br> <br> * Other names: Pulsatile GnRH pump;|
| Active Comparator: combination gonadotropin therapy<br>combined human chorionic gonadotropin (hCG)/urinary Follicle-Stimulating Hormone (uFSH) therapy:HCG treatment was maintained alone for 6 months and then uFSH was added for the next 12 months | Drug: Human chorionic gonadotropin<br>* Human chorionic gonadotropin (hCG)<br>Drug: Urinary Follicle-Stimulating Hormone<br>* Urinary Follicle-Stimulating Hormone (uFSH)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pregnancy in the female partner |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| first appearance of sperm (month after treatment) |  | 18 months | 
| first time with sperm density>1*10^6/ml（month after treatment） |  | 18 months | 
| first time with sperm density>15*10^6/ml（month after treatment） |  | 18 months |