Effect of pubertal induction with combined gonadotropin therapy on testes development and spermatogenesis in males with gonadotropin deficiency: a cohort study

Abstract

STUDY QUESTION: Are recombinant FSH (rFSH) and hCG effective therapies for promoting testicular growth and spermatogenesis inmale adolescents and young adults with gonadotropin deficiency?SUMMARY ANSWER: Combined gonadotropin therapy is effective in inducing puberty and promoting spermatogenesis in male adolescentsand young adults with gonadotropin deficiency and has the potential to improve adult outcomes relating to both fertilityand quality of life.WHAT IS KNOWN ALREADY: Deficiency of pituitary gonadotropins (LH and FSH) due to hypogonadotropic hypogonadism (HH) canresult in poor testicular development, low testicular volumes, micropenis and cryptorchidism. Inadequate hormonal replacementcan lead to long-term issues, including subfertility or infertility, and reduced quality of life. Exogenous testosterone for pubertal inductioncan elevate serum testosterone concentrations and induce virilization, but it does not promote testicular development norinduce spermatogenesis. Fertility and testes growth remain primary concerns for patients seeking treatment.STUDY DESIGN, SIZE, DURATION: We conducted a retrospective observational review of male adolescents and young adults withgonadotropin deficiency and seeking puberty replacement therapy at two large tertiary centre hospitals in London, UK, from 2010to 2024.PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 35 males, with diagnosis of congenital hypogonadotropic hypogonadism(CHH: n¼23; further subdivided into those with partial [pHH: n¼8] and those with complete gonadotropin deficiency [cHH:n¼15]), acquired HH (AHH: n¼4) or Kallmann syndrome (KS: n¼8), received combined gonadotropin therapy. We assessed testiculargrowth and semen quality post-treatment.MAIN RESULTS AND THE ROLE OF CHANCE: The majority of patients were referred for pubertal delay, alone or in combination withcryptorchidism, micropenis or microorchidism. Out of 35 patients, 22 (63%) had previously received testosterone, and the medianage at gonadotropin treatment initiation was 15.8 years (range: 11.8–22.7). Semen analysis was obtained in 18 out of 19 patients whohad received gonadotropin therapy for a median treatment duration of 21.1 months (range: 4.5–66.9) for rFSH and 19.5 months (range:8.3–61.1) for hCG. The median sperm count on semen analysis was 8.9 × 106/ml (range: 0.0–54.9). Significant increases were noted intesticular volume (median change after therapy: 10.5 ml [95% CI 9.5–13.6], P<0.0001), testosterone (median increase: 25.7 nmol/l [95%CI 19.8–31.5], P<0.0001) and inhibin B levels (67.7 pg/ml [95% CI 18.4–86.7], P¼0.0008).