Gonadotropin administration to mimic mini-puberty in hypogonadotropic males: pump or injections?

Author:

Avril Tristan1ORCID,Hennocq Quentin2,Lambert Anne-Sophie1,Leger Juliane34ORCID,Simon Dominique3,Martinerie Laetitia345,Bouvattier Claire156

Affiliation:

1. Pediatric Endocrinology Department, CHU Bicetre, Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Disease CRMR DevGen, Le Kremlin Bicêtre, Paris, France

2. Datascience platform, Imagine Institute, Université Paris Cité, Paris, France

3. Pediatric Endocrinology Department, CHU Robert Debré, Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Disease CRMR de la Croissance et du Développement, Paris, France

4. Université Paris Cité, Faculté de Santé, UFR de Médecine, Paris, France

5. Inserm UMR1185, Le Kremlin Bicetre, Paris, France

6. Paris-Saclay University, Paris, France

Abstract

Objective Newborns with congenital hypogonadotropic hypogonadism (CHH) have an impaired postnatal activation of the gonadotropic axis. Substitutive therapy with recombinant gonadotropins can be proposed to mimic physiological male mini-puberty during the first months of life. The aim of this study was to compare the clinical and biological efficacy of two treatment modalities of gonadotropins administration during mini-puberty in CHH neonates. Design Multicenter retrospective analytical epidemiological study comparing two treatments, pump vs injection, between 2004 and 2019. Methods Clinical (penile size, testis size, testicular descent) and biological parameters (serum concentrations of testosterone, anti-Müllerian hormone (AMH) and Inhibin B) were compared between the two groups by multivariate analyses. Results Thirty-five patients were included. A significantly higher increase in penile length and testosterone level was observed in the injection group compared to the pump group (+0.16 ± 0.02 mm vs +0.10 ± 0.02 mm per day, P = 0.002; and +0.04 ± 0.007 ng/mL vs +0.01 ± 0.008 ng/mL per day, P = 0.001). In both groups, significant increases in penile length and width, testosterone, AMH, and Inhibin B levels were observed, as well as improved testicular descent (odds ratio of not being in a scrotal position at the end of treatment = 0.97 (0.96; 0.99)). Conclusions Early postnatal administration of recombinant gonadotropins in CHH boys is effective in stimulating penile growth, Sertoli cell proliferation, and testicular descent, with both treatment modalities.

Publisher

Bioscientifica

Subject

Endocrinology,Endocrinology, Diabetes and Metabolism,Internal Medicine

Reference22 articles.

1. Congenital hypogonadotrophic hypogonadism: minipuberty and the case for neonatal diagnosis;Swee,2019

2. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment;Boehm,2015

3. Sertoli cell number defines and predicts germ and Leydig cell population sizes in the adult mouse testis;Rebourcet,2017

4. Evidence from Sertoli cell-depleted rats indicates that spermatid number in adults depends on numbers of Sertoli cells produced during perinatal development;Orth,1988

5. Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood;Sharpe,2003

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