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

Phase 4

• Conditions: Idiopathic Hypogonadotropic Hypogonadism
• Interventions: Drug: Pulsatile Gonadotropin Releasing Hormone; Drug: Human chorionic gonadotropin; Drug: Urinary Follicle-Stimulating Hormone

• Registration Number: NCT02310074
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

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

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.

Study Timeline

• Study Start: 2010-01
• Primary Completion: 2014-06
• Status Verified: 2014-12
• Study First Submitted: 2014-12-03
• Study First Submitted QC: 2014-12-04
• Study First Posted: 2014-12-05
• Last Update Submitted: 2015-01-31
• Last Update Posted: 2015-02-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 76

Inclusion Criteria

1. Age greater than 16 yr
2. Diagnosed as idiopathic hypogonadotropic hypogonadism with clinical signs or symptoms of hypogonadism
3. Hypogonadal serum testosterone levels (<166ng/dl) in the presence of low or normal gonadotropins
4. Normal levels of other anterior pituitary hormones
5. Normal MRI scans of the hypothalamo-pituitary region
6. Had discontinued any prior treatment (testosterone or gonadotropin therapy) for at least three months before enrollment

Exclusion Criteria

1. With any significant medical condition (including malignant disease), laboratory abnormality, or psychiatric disorders that will prevent the subject from participating in the study
2. Congenital hypopituitarism
3. Any medical or surgical conditions possibly affecting the experiment result
4. Any clinically significant allergic diseases or allergic to the study drugs
5. Recently drug or alcohol abuse(>35unit/week,1unit=8 g alcohol@1 standard drink@250ml beer@140ml wine@25ml strong alcohol drink like whiskey.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
combination gonadotropin therapy	Urinary Follicle-Stimulating Hormone	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
Pulsatile Gonadotropin Releasing Hormone	Pulsatile Gonadotropin Releasing Hormone	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.
combination gonadotropin therapy	Human chorionic gonadotropin	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

Primary Outcome Measures

Name	Time	Method
pregnancy in the female partner	18 months

Secondary Outcome Measures

Name	Time	Method
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