Estrogen receptor antagonism uncovers gender-dimorphic suppression of whole body fat oxidation in humans: differential effects of tamoxifen on the GH and gonadal axes

Abstract

ContextTamoxifen, a selective estrogen receptor modulator, suppresses GH secretion in women but not in men. It increases testosterone levels in men. As GH and testosterone stimulate fat metabolism, the metabolic consequences of tamoxifen may be greater in women than in men.ObjectiveTo determine whether tamoxifen suppresses fat oxidation (Fox) to a greater degree in women than in men.DesignAn open-label study of ten healthy postmenopausal women and ten healthy men receiving 2-week treatment with tamoxifen (20 mg/day).Endpoint measuresGH response to arginine stimulation, serum levels of IGF1, testosterone and LH (men only), sex hormone binding globulin (SHBG) and whole body basal and postprandial Fox.ResultsIn women, tamoxifen significantly reduced the mean GH response to arginine stimulation (Δ −87%,P<0.05) and circulating IGF1 levels (Δ −23.5±5.4%,P<0.01). Tamoxifen reduced postprandial Fox in women (Δ −34.6±10.3%;P<0.05). In men, tamoxifen did not affect the GH response to arginine stimulation but significantly reduced mean IGF1 levels (Δ −24.8±6.1%,P<0.01). Tamoxifen increased mean testosterone levels (Δ 52±14.2%;P<0.01). Fox was not significantly affected by tamoxifen in men.ConclusionTamoxifen attenuated the GH response to stimulation and reduced postprandial Fox in women but not in men. We conclude that at a therapeutic dose, the suppressive effect of tamoxifen on fat metabolism is gender-dependent. Higher testosterone levels may mitigate the suppression of GH secretion and Fox during tamoxifen treatment in men.