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

Tongji Hospital

Status and phase: Enrolling; Phase 4

Conditions: Isolated Hypogonadotropic Hypogonadism; Infertility; Kallmann Syndrome

Treatments: Drug: Human Chorionic Gonadotropin; Drug: human menopausal gonadotropin

Study type: Interventional

Funder types: Other

Identifiers

NCT03687606

TJ-IRB20180906

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 210 estimated patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18, ≤ 45 years old;
2. Adolescent dysplasia or loss of puberty: Genital Tanner score ﹤ 5, pubic hair Tanner score ﹤ 5;
3. 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);
4. With or without olfactory loss/reduction;
5. Other pituitary hormone levels are normal;
6. Head MRI examination is normal;
7. Fertility is desired currently or will be desired in the future;
8. Understand and sign the informed consent form.

Exclusion criteria

1. Primary hypogonadism;
2. Acquired hypogonadotrophic hypogonadism;
3. A history of treatment with pulsed GnRH, hCG and FSH related hormones;
4. Receive testosterone replacement therapy for more than 6 months;
5. History of cryptorchidism or cryptorchidism;
6. The sperm density before treatment ≥1×10^6/ml;
7. Moderate or severe liver and kidney dysfunction (ALT>120IU/L, AST>80IU/L, CR>115μmol/L);
8. The karyotype is 45,X or 47,XXY and 48, XXXY and other abnormal karyotypes;
9. True hermaphroditism and pseudohermaphroditism;
10. Sex hormone abnormalities caused by adrenal lesions;
11. Hypogonadism secondary to other systemic diseases;
12. Abnormal secretion of hormones caused by brain lesions (such as pituitary tumors);
13. There are other hormone abnormalities in the pituitary;
14. There are contraindications for the treatment with hCG or hMG.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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210 participants in 3 patient groups

Human Chorionic Gonadotropin alone

Active Comparator group

Description:

Human Chorionic Gonadotropin 2000U\~6000U, intramuscular injection, two times per week for 3 years.

Treatment:

Drug: Human Chorionic Gonadotropin

hCG alone for 6 months then hMG added

Experimental group

Description:

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.

Treatment:

Drug: human menopausal gonadotropin

Drug: Human Chorionic Gonadotropin

hCG and hMG

Experimental group

Description:

Human Chorionic Gonadotropin 2000U\~6000U and 75\~150IU human menopausal gonadotropin, intramuscular injection, two times per week for 3 years.

Treatment:

Drug: human menopausal gonadotropin

Drug: Human Chorionic Gonadotropin