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

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

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.

Study Overview

• Status: Unknown
• Conditions: Idiopathic Hypogonadotropic Hypogonadism
• Intervention / Treatment: Drug: Pulsatile Gonadotropin Releasing Hormone; Drug: Human chorionic gonadotropin; Drug: Urinary Follicle-Stimulating Hormone

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 Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Pulsatile Gonadotropin Releasing Hormone; Other Names: Pulsatile GnRH pump
Active Comparator: combination gonadotropin therapy; 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; Human chorionic gonadotropin (hCG); Drug: Urinary Follicle-Stimulating Hormone; Urinary Follicle-Stimulating Hormone (uFSH)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
pregnancy in the female partner	18 months

Secondary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
testicular volume		18 months
prostatic volume		18 months
Tanner stage for pubic hair		18 months
Tanner stage for genital		18 months
serum hormone levels	especially serum testosterone, LH, and FSH levels	18 months
sperm concentration per ejaculate		18 months
adverse events		18 months

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Guang Ning, MD, PhD, Shanghai Jiao Tong University School of Medicine

Publications and helpful links

General Publications

• Yang YY, Zheng SC, Wang WC, Yang ZW, Shan C, Zhang YW, Qi Y, Chen YH, Gu WQ, Wang WQ, Zhao HY, Liu JM, Sun SY. Osteocalcin Levels in Male Idiopathic Hypogonadotropic Hypogonadism: Relationship With the Testosterone Secretion and Metabolic Profiles. Front Endocrinol (Lausanne). 2019 Oct 11;10:687. doi: 10.3389/fendo.2019.00687. eCollection 2019.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: December 3, 2014
• First Submitted That Met QC Criteria: December 4, 2014
• First Posted (Estimate): December 5, 2014

Study Record Updates

• Last Update Posted (Estimate): February 3, 2015
• Last Update Submitted That Met QC Criteria: January 31, 2015
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Reproductive Control Agents; Follicle Stimulating Hormone; Hormones; Chorionic Gonadotropin
• Other Study ID Numbers: ruijin-GnRH pump-002