Endocrine Abstracts

Hypogonadotropic hypogonadism (HH) is a rare reproductive disorder that results in a lack of normal pubertal development and reduced potential for fertility in adult life. The condition is characterised by low circulating sex steroid concentrations resulting from a deficiency of pituitary gonadotropin production. HH may be congenital or acquired, most commonly due to tumour or treatment for malignant disease. When associated with anosmia it is termed Kallmann syndrome. HH is also seen as part of a syndrome or alongside other pituitary hormone defects. Induction of puberty in male adolescent patients with HH has traditionally been with low and increasing doses of testosterone from the age of 12 years. However, whilst this management can induce virilization, it will not promote testis growth nor the potential for spermatogenesis. Recent robust evidence has demonstrated the efficacy and tolerance of the use of subcutaneous human chorionic gonadotropin (hCG) together with recombinant follicle-stimulating hormone (rFSH) to induce male puberty. Particularly for those with cryptorchidism and pre-pubertal testicular volumes, pre-treatment with rFSH is important to promote expansion of the Sertoli cell population to optimise capacity for sperm production. At present there is no national or international guideline for pubertal induction with gonadotropins in males with HH. A recent BSPED survey (n=18, from 13 centres) showed interest in a suitable guideline in 100% of responders and that the current barrier to gonadotropin use for this indication is lack of expertise or protocol in 88%. Through a multicentre approach, we have developed a practical protocol for paediatric endocrinologists for induction of puberty in male patients with this condition. The protocol includes two separate arms for patients with testes volumes of < or ≥ 6mls, with pre-treatment with rFSH in the former group and initial monotherapy with hCG in the latter group (with addition of rFSH as required). Parameters for monitoring, dose adjustments and management of side-effects are addressed. In summary, we present an evidence-based multicentre developed guideline for the induction of puberty with gonadotropins in males with HH, which can be used in tertiary endocrine settings across the UK to improve fertility outcomes in this patient group.