Effects of transdermal testosterone gel or an aromatase inhibitor on serum concentration and pulsatility of growth hormone in older men with age-related low testosterone

Growth hormone is the major regulator of growth and body composition. Pulsatile GH secretion declines exponentially with age. Testosterone replacement is being increasingly offered to older men with age-related low testosterone. Testosterone administration has been shown to stimulate GH secretion. However, little is known about the effect of testosterone aromatization to estradiol on GH pulsatility and its impact on IGF-1 in older men. Objective This randomized controlled proof-of-concept trial investigated the relative effects of testosterone and estradiol on GH pulsatility and IGF-1 in older men with low testosterone. Design Thirty-seven men, ≥ 65 years with total testosterone < 350 ng/dL were randomized to 5 g transdermal testosterone gel (TT), 1 mg oral aromatase inhibitor (AI) or placebo daily for 12 months. Primary outcome was deconvolution and approximate entropy analyses of pulsatile including basal and entropic modes of secretion performed at baseline and 3 months. Secondary outcomes included IGF-1 evaluated at baseline, 3 and 6 months. Results At 3 months, mean GH and in IGF-1 were similar between the three groups. At 6 months, IGF-1 significantly increased by Δ 15.3 ± 10.3 ng/ml in the TT-group compared to placebo (P = 0.03). Both intervention groups significantly increased GH pulse frequency (TT-group, P = 0.04; AI-group, P = 0.05) compared to placebo. The GH secretory-burst mode (duration) significantly decreased in the TT-group (P = 0.0018) compared to placebo while it remained unchanged in the AI-group (P = 0.059). Conclusions In older men, testosterone increases GH pulse frequency while the aromatization to estradiol is involved in the rise of IGF-1 levels.