Endocrine Abstracts

Introduction: The hypothalamic-pituitary-testicular (HPT) axis is highly active in healthy male newborns until 3-6 months of age. During this phase, namely ‘minipuberty,’ Sertoli cells are stimulated by follicle-stimulating hormone (FSH), increasing testis volume and serum levels of AMH and inhibin B. In addition, luteinizing hormone (LH) promotes testosterone synthesis in Leydig cells, contributing to normal penis size and testicular position in the scrotum. In congenital hypogonadotropic hypogonadism (CHH) minipuberty is absent due to gonadotropin deficiency. Whilst standard treatment is with testosterone replacement, recent literature on treatment with recombinant gonadotropins to replace minipuberty is encouraging. This study describes the impact of recombinant FSH (r-FSH), with human Chorionic Gonadotropin (hCG) or recombinant LH (r-LH), in male infants with CHH or combined pituitary hormone deficiency (CPHD) treated during minipuberty.

Methods: A longitudinal retrospective study of a UK male CHH cohort managed during minipuberty at Barts Health NHS Trust.

Objective: To assess changes in penis size, testis volume and position, serum levels of LH, FSH, testosterone, AMH, and inhibin B, recorded in our bespoke REDCap database.

Results: Five male infants with CHH or CPHD received recombinant gonadotropic therapy during minipuberty (median age 0.4; range 0.2-0.6 years). All had micropenis and microorchidism (testes volume ≤0.4 mL by ultrasonography), and four had cryptorchidism. No adverse effects were observed. Post-treatment with r-FSH combined with hCG or r-LH, marked increments were observed in penis length (median increase 12.5; range 2.0-25 mm), testicular volume (median increase 0.3; range 0.1-1.13 cc), serum FSH (median increase 22.7; range 0.0-55.0 IU/l), and inhibin B (median increase 256; range 36.9-605.1 pg/ml). Improvements in testes position, serum LH and testosterone concentrations were more variable, with 2 patients showing improvements in testes position, whether into scrotum or distal inguinal canal.

Discussion: Our findings support the potential benefits of recombinant gonadotropic therapy to replace minipuberty in infants with CHH, by stimulating Sertoli cell populations and resolving micropenis. In this small series the best outcomes were seen with combined r-LH/r-FSH therapy for 4 months. Combined gonadotropins have the potential to facilitate future fertility in infants with CHH, but long term follow data are needed.