Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of long term use of hCG alone or hCG plus hMG in the treatment of male patients with isolated hypogonadotropic hypogonadism (IHH). One third of the participants will receive hCG treatment alone and the other third of the participants will receive hCG treatment alone for six months, then the hMG will be added. And the last third of the participants will receive hCG and hMG treatment since the beginning of the treatment.

Detailed Description
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The efficacy of hCG alone or hCG plus hMG in the treatment of male IHH patients was reported in some studies. However, these studies were mostly non-randomized controlled studies with small size of samples and short follow-up time. There was also no reported study which aimed to compare the efficacy and safety of long term use of hCG or hCG plus hMG in the treatment of male patients with IHH. So the difference in the efficacy and safety between long term use of hCG alone and hCG plus hMG in the treatment of IHH is unknown. In different reported studies, the hCG plus hMG treatment had two regimens: using hCG alone for six month, then hMG was added and using hCG plus hMG since the beginning of the treatment. The difference in the efficacy and safety between the above two regimes is also unknown.

Official Title
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Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in the Treatment of Male Patients With Isolated Hypogonadotropic Hypogonadism: an Open, Randomized Controlled Study

Conditions
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Kallmann Syndrome, Isolated Hypogonadotropic Hypogonadism, Infertility

Intervention / Treatment
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* Drug: Human Chorionic Gonadotropin
* Drug: human menopausal gonadotropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18, ≤ 45 years old; Adolescent dysplasia or loss of puberty: Genital Tanner score ﹤ 5, pubic hair Tanner score ﹤ 5; Serum FSH and LH levels are low or in normal low value, testosterone was lower than normal range (1.75ng / ml, the lower limit of the normal blood testosterone reference range of Tongji Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology); With or without olfactory loss/reduction; Other pituitary hormone levels are normal; Head MRI examination is normal; Fertility is desired currently or will be desired in the future; Understand and sign the informed consent form. Exclusion Criteria: Primary hypogonadism; Acquired hypogonadotrophic hypogonadism; A history of treatment with pulsed GnRH, hCG and FSH related hormones; Receive testosterone replacement therapy for more than 6 months; History of cryptorchidism or cryptorchidism; The sperm density before treatment ≥1×10^6/ml; Moderate or severe liver and kidney dysfunction (ALT>120IU/L, AST>80IU/L, CR>115μmol/L); The karyotype is 45,X or 47,XXY and 48, XXXY and other abnormal karyotypes; True hermaphroditism and pseudohermaphroditism; Sex hormone abnormalities caused by adrenal lesions; Hypogonadism secondary to other systemic diseases; Abnormal secretion of hormones caused by brain lesions (such as pituitary tumors); There are other hormone abnormalities in the pituitary; There are contraindications for the treatment with hCG or hMG.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Human Chorionic Gonadotropin alone<br>Human Chorionic Gonadotropin 2000U 6000U, intramuscular injection, two times per week for 3 years. | Drug: Human Chorionic Gonadotropin<br>* White freeze-dried cake or powder with specifications of 1000U, 2000U, 5000U.<br>* Other names: hCG;|
| Experimental: hCG alone for 6 months then hMG added<br>Human Chorionic Gonadotropin 2000U 6000U, intramuscular injection, two times per week for six months, then 75 150IU human menopausal gonadotropin, intramuscular injection, two times per week, was added and last for the next 30 months. | Drug: Human Chorionic Gonadotropin<br>* White freeze-dried cake or powder with specifications of 1000U, 2000U, 5000U.<br>* Other names: hCG;Drug: human menopausal gonadotropin<br>* White freeze-dried cake or powder with specification of 75IU.<br>* Other names: hMG;|
| Experimental: hCG and hMG<br>Human Chorionic Gonadotropin 2000U 6000U and 75 150IU human menopausal gonadotropin, intramuscular injection, two times per week for 3 years. | Drug: Human Chorionic Gonadotropin<br>* White freeze-dried cake or powder with specifications of 1000U, 2000U, 5000U.<br>* Other names: hCG;Drug: human menopausal gonadotropin<br>* White freeze-dried cake or powder with specification of 75IU.<br>* Other names: hMG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sperm density | Sperm density will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits. | 6 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semen volume | Sperm volume will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits. | 6 months. | 
| Sperm activity | Sperm activity will be obtained in the semen sample analysis using the World Health Organization (WHO) normal values based on the WHO 2010 reference limits. | 6 months. | 
| The time for sperm to appear during treatment | The time for the sperm firstly appeared in the semen will be recorded. | 6 months. | 
| Serum testosterone levels | The serum testosterone levels will be tested in every visit. | 3 months. | 
| Testicular volume | Testicular volume will be measured using a Prader orchidometer. | 3 months. | 
| Penis length | Penis length will be measured from the pubic symphysis to glans using a vernier caliper. | 3 months. | 
| Pubic hair | Pubic hair will be evaluated according to Tanner pubertal stages. | 3 months. | 
| Genitalia | Genitalia will be evaluated according to Tanner pubertal stages. | 3 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gonadotropin treatment, human chorionic gonadotropin, human menopausal gonadotropin