Acute estrogen exposure does not affect basal very low-density lipoprotein-triglyceride production or oxidation in postmenopausal women.
BACKGROUND
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.
Gormsen
Lars C
LC
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, DK-8000 Aarhus, Denmark. lars.christian.gormsen@ki.au.dk
Høst
Christian
C
Hjerrild
Britta Eilersen
BE
Gravholt
Claus H
CH
Nielsen
Søren
S
D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008079:Lipoproteins, VLDL / Q000097:blood*; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D017698:Postmenopause / Q000097:blood* / Q000187:drug effects*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*
D004967:Estrogens; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D004958:Estradiol