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

CONTEXT Long-term hormone replacement therapy (HRT) with estradiol (E(2)) 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. OBJECTIVE To study the in vivo effect of a single dose of E(2) on VLDL-TG kinetics and oxidation in humans. METHODS Eight healthy, postmenopausal women were given a single dose of either placebo or E(2) (4 mg) orally. VLDL-TG kinetics was assessed by a 240-min primed-continuous infusion of ex vivo labeled [1-(14)C]triolein-labeled VLDL. Fractional and absolute VLDL-TG oxidation was determined by hyamin trapping of exhaled (14)C label. Indirect calorimetry provided measurements of lipid oxidation. RESULTS Administration of 4 mg of E(2) orally rapidly increased plasma E(2) concentrations 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 E(2)): 20.0+/-12.4 vs 24.1+/-10.7 micromol/min, P=0.33; VLDL-TG oxidation: 12.3+/-10.9 vs 12.6+/-5.6 micromol/min, P=0.93); or VLDL-TG clearance rates: 51.4+/-16.8 vs 64.9+/-28.8 ml/min, P=0.34). CONCLUSIONS Short-term E(2) elevation 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.