Aromatized Estrogens Amplify Nocturnal Growth Hormone Secretion in Testosterone-Replaced Older Hypogonadal Men

Context: Testosterone (T) increases GH secretion in older men with a relative lack of T, in hypogonadal men of all ages, and in patients undergoing sex reassignment. The role of estradiol (E₂) in men is less well defined. Objective: To assess the contribution of aromatization of T to spontaneous nocturnal and stimulated GH secretion. Participants: Four groups of healthy older men (N = 74, age range 57 to 77 years) were studied. The gonadotropic axis was clamped with the gonadotropin-releasing hormone antagonist degarelix. Three groups received T and one group placebo addback. Two T-replaced groups were treated with anastrozole (an aromatase inhibitor) and either placebo or E₂ addback. Main Outcome Measures: Ten-minute GH concentration profiles were quantified by deconvolution analysis, after overnight (2200 to 0800 hours) sampling, and after combined IV injection of GHRH (0.3 μg/kg) and GHRH-2 (0.3 μg/kg) and withdrawal of a 2-hour somatostatin infusion (1 μg/kg/h). Results: E₂ addback during aromatase inhibition increased basal (P = 0.046), pulsatile (P = 0.020), and total (P = 0.018) GH secretion by 60% to 70%. E₂ did not potentiate GH secretory stimuli. Logarithmically transformed pulsatile GH secretion correlated strongly and positively with concurrent E₂ concentrations overall (P = 0.028) and under anastrozole treatment (P = 0.005). Conclusion: E₂ administration in older men transdermally stimulates overnight pulsatile GH secretion. The exact site of E₂ action cannot be ascertained from these experiments but may include hypothalamic loci involved in GH regulation, especially because GH secretagogue effects on somatotrope pituitary cells were not affected.