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Gonadotropin Therapy for Mini-Puberty Induction in Male Infants With Hypogonadotropic Hypogonadism
Sophie Rhys-Evans1, Francesco d'Aniello1,2,3, Emma C Alexander4
1Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ London, UK.
Insights
Gonadotropin therapy effectively induces mini-puberty in male infants with congenital hypogonadotropic hypogonadism (CHH), improving penile length and testicular descent. This treatment shows promise for CHH management in early life.
Area of Science:
- Pediatric Endocrinology
- Reproductive Medicine
- Genetics
Background:
- Congenital hypogonadotropic hypogonadism (CHH) is characterized by isolated gonadotropin deficiency.
- Mini-puberty, a transient postnatal activation of the hypothalamic-pituitary-gonadal axis, offers a critical window for CHH diagnosis and treatment in infants.
- Current CHH treatment in male infants primarily uses testosterone for phallus size, but gonadotropins may offer additional benefits for testicular development.
Purpose of the Study:
- To systematically review the effectiveness of gonadotropin therapy in stimulating mini-puberty related outcomes in male infants diagnosed with CHH.
- To evaluate the impact of gonadotropins on penile length, testicular descent, and hormonal markers during the mini-puberty phase.
Main Methods:
- A systematic review was conducted across 11 databases following PRISMA guidelines, with evidence quality assessed using the Cochrane Risk of Bias tool.
- Eleven studies involving 71 male infants, including those with Kallmann syndrome, were included.
- Data synthesis combined outcomes from continuous subcutaneous infusion and subcutaneous injection administration of gonadotropins.
Main Results:
- Gonadotropin therapy in male infants with CHH led to a statistically significant increase in penile length and inhibin B concentration (P = .0007).
- Partial or complete testicular descent was observed in 73% of patients treated with gonadotropins.
- The median age at treatment initiation was 4.2 months, with follow-up ranging from 3 to 10 years.
Conclusions:
- This systematic review provides evidence supporting the efficacy of gonadotropins in inducing mini-puberty outcomes in male infants with CHH.
- Gonadotropin therapy demonstrates potential for promoting testicular descent and development in this population.
- Limitations include data variability and diverse treatment modalities, impacting reliability and generalizability.
Context:
Congenital hypogonadotropic hypogonadism (CHH) is defined as an isolated deficiency of gonadotropin hormones. Mini-puberty, a transient postnatal activation of the hypothalamic-pituitary-gonadal axis in healthy infants, provides a window of opportunity to diagnose and treat CHH. Currently, in male infants with CHH, testosterone is used to increase phallus size. However, gonadotropin replacement could additionally promote testicular descent and development, particularly relating to Sertoli cells. We conducted a systematic review of the effectiveness of gonadotropin therapy in stimulating mini-puberty related outcomes in male infants with CHH.
Evidence Acquisition:
In line with PRISMA guidelines, a systematic review of 11 databases was carried out (August 2023). Evidence quality was assessed using the Cochrane Risk of Bias for Non-Randomised Studies of Interventions tool. Protocol registered on PROSPERO (CRD42023453080).
Evidence Synthesis:
After a double-consensus screen of 767 abstracts and 66 full texts, 11 studies were included from 7 countries. A total of 71 male infants were enrolled, 12 with Kallmann syndrome. Median age at treatment initiation was 4.2 months (range, 0.25-57 months) and follow-up ranged from 3 to 10 years. Gonadotropin therapy was administered using continuous subcutaneous infusion (n = 35) or subcutaneous injection (n = 36). Due to treatment variability, modalities were combined for data synthesis. Gonadotropins induced a statistically significant increase in penile length and inhibin B concentration (P = .0007) and led to partial or full testicular descent in 73% (n = 62) of patients.
Conclusion:
This systematic review provides unique evidence supporting the efficacy of gonadotropins for induction of mini-puberty. However, the reliability and generalizability are limited due to disparate data and treatment modality variation.
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