Efficacy and Safety of Human Chorionic Gonadotropin Combined with Human Menopausal Gonadotropin and a Gonadotropin-Releasing Hormone Pump for Male Adolescents with Congenital Hypogonadotropic Hypogonadism
Congenital hypogonadotropic hypogonadism (CHH) is a disorder characterized by insufficient release and secretion of gonadotropin-releasing hormone (GnRH). This condition can manifest in two subtypes: Kallmann syndrome (KS), which is associated with olfactory dysfunction, and normosmic idiopathic hypogonadotropic hypogonadism (nIHH), which retains intact olfactory function without other intracranial pathologies. The incidence of CHH ranges from 1 to 10 per 100,000 individuals, with a male to female ratio of 5:1. The disorder can lead to a range of clinical issues, including cryptorchidism, a small penis, and scrotal dysplasia, which can be observed at birth. Without timely intervention, CHH patients often exhibit a poor response to spermatogenic therapy in adulthood.
The primary goal of treating CHH is to induce puberty and, where possible, to restore fertility. Traditional treatment options include the use of a GnRH pump, the combination of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and testosterone replacement therapy. While testosterone replacement can promote the development of secondary sexual characteristics, it does not improve fertility. Given the high priority placed on fertility by patients, particularly in China, alternative treatments that can stimulate both testosterone production and spermatogenesis are highly sought after.
This study aimed to evaluate the feasibility and efficacy of hCG/hMG therapy compared to GnRH pump therapy in male adolescents with CHH. The study enrolled 41 patients aged between 12 and 18 years, who were divided into two groups: one receiving hCG/hMG therapy (n = 20) and the other receiving GnRH pump therapy (n = 21). The treatment was divided into a study phase (0–3 months) and a follow-up phase (3–12 months). Key parameters such as testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were monitored and compared between the two groups.
Before treatment, there were no significant differences between the two groups in terms of biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV in the hCG/hMG group increased to 5.1 ± 2.3 mL, compared to 4.1 ± 1.8 mL in the GnRH group, though this difference was not statistically significant (P > 0.05). However, significant differences were observed in PL and PD, with the hCG/hMG group showing greater increases (PL: 6.9 ± 1.8 cm vs. 5.1 ± 1.6 cm; PD: 2.4 ± 0.5 cm vs. 2.0 ± 0.6 cm; P < 0.05 for both). By the end of 6 months, biomarkers in both groups were within the normal range, but the hCG/hMG group exhibited significantly higher testosterone levels and greater growth in PL and PD compared to the GnRH group (all P < 0.05). After 9 to 12 months of treatment, the testosterone level remained higher in the hCG/hMG group, though other parameters did not show significant differences.
The study concluded that the hCG/hMG regimen is both feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment appear to be a critical window for observing the strongest effects of therapy. Furthermore, the extended follow-up period showed positive outcomes at the 1-year mark, suggesting that the hCG/hMG regimen can be a viable alternative to the GnRH pump. However, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further investigation.
The treatment protocols for both groups were designed based on expert consensus and previous research. For the hCG/hMG group, hCG was administered intramuscularly at doses ranging from 1000 to 2000 units every other day or twice a week, depending on the patient’s response, to maintain testosterone levels between 200 and 500 ng/dL. hMG, containing 75 units of FSH and 75 units of LH, was administered once daily. In the GnRH group, patients received continuous subcutaneous injections of GnRH via a pump, with doses adjusted according to adult hypogonadotropic hypogonadism guidelines.
Safety and compliance were closely monitored throughout the study. Adverse reactions such as acne, frequent penile erections, and skin infections were noted in a few patients, but these were managed by adjusting the hCG dose. Compliance was generally good, with most patients adhering to the treatment regimen without significant interruptions.
The study also highlighted the importance of early diagnosis and treatment in CHH patients. Early intervention not only aids in the development of secondary sexual characteristics but also helps preserve adult reproductive function. The hCG/hMG regimen, being simpler and more convenient than the GnRH pump, offers a practical alternative for adolescent patients who may prefer injections over wearing a pump.
In summary, this study provides valuable insights into the treatment of CHH in male adolescents, demonstrating that hCG/hMG therapy is a safe and effective option. The findings suggest that this regimen can be particularly beneficial in the early stages of treatment, offering significant improvements in key parameters such as testosterone levels, penile length, and penis diameter. However, further research is needed to explore the long-term outcomes and potential limitations of this treatment approach.
doi.org/10.1097/CM9.0000000000001419
Was this helpful?
0 / 0