Acute estrogen exposure does not affect basal very low-density lipoprotein–triglyceride production or oxidation in postmenopausal women

Abstract

ContextLong-term hormone replacement therapy (HRT) with estradiol (E2) is associated with an altered lipid profile including unfavorable increases in triglyceride (TG) concentrations and augmented hepatic very low-density lipoprotein (VLDL)–TG production. There are indications that this effect of estrogens may be immediate.ObjectiveTo study thein vivoeffect of a single dose of E2on VLDL–TG kinetics and oxidation in humans.MethodsEight healthy, postmenopausal women were given a single dose of either placebo or E2(4 mg) orally. VLDL–TG kinetics was assessed by a 240-min primed-continuous infusion ofex vivolabeled [1-14C]triolein-labeled VLDL. Fractional and absolute VLDL–TG oxidation was determined by hyamin trapping of exhaled14C label. Indirect calorimetry provided measurements of lipid oxidation.ResultsAdministration of 4 mg of E2orally rapidly increased plasma E2concentrations from below detection threshold to premenopausal levels. Free fatty acids (FFA) and TG concentrations were unaltered. No immediate effect was observed on either VLDL–TG production (placebo versus E2): 20.0±12.4 vs 24.1±10.7 μmol/min,P=0.33; VLDL–TG oxidation: 12.3±10.9 vs 12.6±5.6 μmol/min,P=0.93); or VLDL–TG clearance rates: 51.4±16.8 vs 64.9±28.8 ml/min,P=0.34).ConclusionsShort-term E2elevation does not affect VLDL–TG production, oxidation, or clearance in humans. We therefore propose that HRT-associated dyslipidemia has a gradual rather than immediate onset.