LH 3 Hours Post Depot Triptorelin for Monitoring Therapy in Central Precocious Puberty (CPP) Related to Suppression of Ovarian Steroidogenesis

FREIRE, ANALÍA; GRYNGARTEN M; ARCARI, ANDREA; BALLERINI MG; ESCOBAR, MARÍA EUGENIA; BERGADÁ I; ROPELATO, M.G.

Playa del Carmen

Congreso; XXIV Reuniòn de la Sociedad Latinoamericana de Endocrinología Pediátrica; 2014

Depot GnRH-analogues (GnRHa) represent the first-line of therapy in central precocious puberty (CPP). Stimulated LH post GnRH or GnRHa has been proposed for monitoring treatment, however there is no consensus on the criteria of inhibition of gonadotropin axis. As the suppression of the estradiol ovarian synthesis is the main objective of the treatment to lead to the involution of pubertal signs and to arrest the accelerated bone maturation, a reliable test to assess the suppression of ovarian estradiol synthesis and to explore the inhibition of the gonadotropic axis suppression could be a useful tool in the management of these patients. Objective: To evaluate the usefulness of stimulated gonadotropins and estradiol levels by using the free fraction of Triptorelin depot for monitoring treatment efficacy of the gonadotropin axis inhibition. Patients and Methods: A prospective and longitudinal study was performed including 37 girls >4 years of age naïve to or under Tritptorelin depot 3.75 mg IM every 28 days for idiopathic CPP. Monitoring visits for clinical and auxological assessement and GnRHa-stimulation testing were performed at 3, 6, 12, 18 and 24 months. Serum LH and FSH were measured at baseline and 3 hours after the intramuscular injection of depot Triptorelin (LH-3 h, FSH-3 h) whereas serum estradiol at 24 hours (E2-24 h) (ECLIACobas e411, Roche) post injection. In order to evaluate the stimulatory effect of the free fraction of GnRHa the response of gonadotropins and estradiol after the first dose were assessed in 11/37 girls. Clinical/auxological criteria of adequate inhibition were: a decrease of the breast size and trophism and vulvar estrogenization at 3 and 6 months, together with deceleration of the growth rate and decrease of BA/CA from12 months and beyond. Percentiles 97 (97 pc) of LH-3h and FSH-3h for 3?6 months and 12?18?24 months of treatment were calculated. Results: The response of gonadotropins and estradiol obtained after the first dose of Triptorelin was pubertal (Table). In 78/81 monitoring visits adequate clinical pubertal inhibition was observed. Responses of gonadotropins and estradiol (mean ± SD) and 97 pc for 3?6 months and 12?18?24 months of treatment are summarized in the table. From 3 months GnRHa treatment, serum stimulated estradiol at 24 h was found close or equal to the limit of detection of the assay (10 pg/mL). Three patients were clinically suspected of inadequate inhibition at 6 months of treatment. These patients showed LH-3 h and/ or FSH-3 h levels over the 97pc observed in the group with adequate treatment and elevated stimulated E2-24 h levels. Conclusion: The first injection of depot Triptorelin due to its free fraction was able to stimulate gonadotropin and ovarian estradiol synthesis to pubertal levels. After successive doses of treatment the assessment of stimulated estradiol showed that GnRHa leads to a profound suppression of ovarian steroidogenesis. These findings allow us to suggest that levels of LH 3 hours post depot Triptorelin below 4.0 IU/L at 3?6 months of treatment, or below 3.3 IU/L after one year of treatment ensure an adequate inhibition of the pituitary-ovarian axis.