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

Context: Tamoxifen, a Selective Estrogen Receptor Modulator, suppresses growth hormone (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. Objective: To determine whether tamoxifen suppresses fat oxidation to a greater degree in women than in men. Design: An open-label study of ten healthy postmenopausal women and ten healthy men receiving 2-week treatment with tamoxifen (20 mg/d). Endpoint measures: GH response to arginine stimulation, serum levels of IGF-I, testosterone and LH (men only), SHBG and whole body basal and postprandial fat oxidation. Results: In women, tamoxifen significantly reduced the mean GH response to arginine stimulation (△ -87%, p<0.05) and circulating IGF-I levels (△ -23.5±5.4%, p<0.01). Tamoxifen reduced postprandial fat oxidation in women (△ -34.6±10.3%; p<0.05). In men, tamoxifen did not affect the GH response to arginine stimulation but significantly reduced mean IGF-I levels (△ -24.8±6.1%, p<0.01). Tamoxifen increased mean testosterone levels (△ 52±14.2%; p<0.01). Fat oxidation was not significantly affected by tamoxifen in men. Conclusion: Tamoxifen attenuated the GH response to stimulation and reduced postprandial fat oxidation 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 fat oxidation during tamoxifen treatment in men.