Long-term treatment of central precocious puberty with an intranasal LHRH analogue: control of pituitary function by urinary gonadotropins

Daily subcutaneous doses of luteinizing hormonereleasing hormone (LHRH) analogues are a well-established therapy for gonadotropin-dependent precocious puberty. Reports on intranasally administered analogues, however, are controversial. We studied the effect of intranasal d-Ser (TBU)⁶-LHRH (BUS) on growth rate, skeletal maturation, and urinary gonadotropins in five girls and one boy with central precocious puberty (CPP) who had been treated for 1.4–2.3 years (mean 1.9). Because of the potential antifertility effects of LHRH analogues, testicular histology was analysed in the boy. In the five children with accelerated growth, the bone age-related velocity of heigh gain decreased from 10.58 ±2.77 to 5.82±1.8 cm/year (means±SD, P<0.01), and the ratio of change in bone age to change in chronological age fell below 1. Basal luteinizing hormone (LH), and LHRH-stimulated LH and follicle stimulating-hormone, at pubertal levels before treatment, decreased significantly in all children, normalizing in four (P<0.04). During therapy, pituitary function was best controlled by urinary LH, which correlated with clinical data. After 13 months of therapy, testicular histology showed degenerated Sertoli cells, and absence of B-and Ap-spermatogonia and of primary spermatocytes in the boy. We conclude that: (1) Efficient long-term suppression of central precocious puberty — including accelerated growth and skeletal maturation — can be maintained by intranasal dosage of BUS. (2) Urinary LH reflects pituitary function and proves to be a reliable guide to adjustment of the LHRH-analogue dose regimen. (3) Testicular atrophy after 1 year of continuous therapy with high doses of BUS raises the question of potential infertility in boys with precocious puberty treated with potent analogues of the LHRH.Abbreviations CPP central precocious puberty - LH luteinizing hormone - FSH tollicle-stimulating hormone - LHRH luteinizing hormone-releasing hormone - LHRH_A LHRH analogue - BUS the analogue d-Ser[TBU]⁶-LHRH (Buserelin), HOE 766) - BA bone age - BA/ CA ratio of change in bone age to change in chronological age - SDS standard deviation score - T urinary testosterone - E2 urinary oestradiol