Endocrine Abstracts

Background: Hypogonadotropic hypogonadism (HH) is a key cause of absent, partial, or arrested puberty. Individuals with HH experience central disorders of the hypothalamic-pituitary-gonadal (HPG) axis, with deficiency in gonadotropin-releasing hormone (GnRH). This leads to inadequate pituitary gonadotropins (luteinising hormone (LH) and follicle-stimulating hormone (FSH)), resulting in immature gonadal development. It has substantial consequences including infertility and reduced quality of life. The mainstay of current therapy is testosterone which facilitates secondary sexual characteristics; however, spermatogenesis is only possible with gonadotropins.

Objective: To evaluate the efficacy of gonadotropin treatment to induce puberty in males with HH as per the local guidelines available on the BSPED website¹. To investigate the outcomes of treatment, using pre-treatment with recombinant (r) FSH for individuals with severe HH, followed by combined rFSH and human chorionic gonadotropin (hCG), and hCG +/- rFSH for patients with partial HH (defined by baseline TV >6ml).

Design: Retrospective analysis conducted on medical records of males diagnosed with HH who received gonadotropin treatment in two large tertiary hospitals (Royal London Hospital and University College London Hospital) from 2011 to 2023.

Outcome Measures: Primary outcome assessed was testicular volume (TV). Secondary outcomes include semen analysis.

Results: A total of 23 males with HH were included, of which 5 have Kallmann syndrome and 2 have HH post-craniopharyngioma. Mean age at start of gonadotropin treatment was 16.89 (± 2.39) years old. 16 patients received pre-treatment with FSH and subsequent hCG/rFSH, and 7 patients received treatment with hCG/rFSH started simultaneously. Mean TV increased from 3.14ml (± 1.74) to 11.63ml (± 5.21) in the group treated with pre-FSH and increased from 7.33ml (± 2.75) to 14.13ml (± 3.71) in the group treated with hCG/FSH. 11 out of 15 males who completed therapy successfully banked sperm. Therapy was well tolerated with only 1 patient choosing to discontinue treatment.

Conclusions: Gonadotropin treatment was effective in inducing or completing puberty in males with HH. Our clinical practice suggests that pre-FSH treatment is a viable option for individuals with TV <6ml, resulting in significant increase in TV. Further prospective studies are warranted to validate these findings and establish standardised treatment guidelines.

¹ BSPED, 2021. https://www.bsped.org.uk/media/1989/protocol-for-induction-of-puberty-with-gonadotropins-in-males-with-gnrh-or-gonadotropin-deficiency_bsped_website-002.pdf