Different effects of oral conjugated equine estrogen and transdermal estrogen replacement therapy on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women.
BACKGROUND
Postmenopausal estrogen replacement therapy (ERT) has an antioxidant effect that opposes the oxidation of LDL particles. Oral ERT-induced increases in plasma triglyceride, however, decrease LDL particle size, which may counteract this antioxidant effect. Because transdermal ERT decreases plasma triglyceride, it may not decrease LDL particle size and may preserve estrogen's antioxidant effect. The present study investigates whether transdermal ERT can eliminate the adverse effects of oral ERT on the size and oxidative susceptibility of LDL in postmenopausal women.


RESULTS
Postmenopausal women received no treatment (n=12) or were treated with either 0.625 mg oral conjugated equine estrogen daily (n=16) or with transdermal estradiol (50 microg/d, n=16) for 3 months. Plasma lipids and the diameter of LDL particles were determined. Susceptibility of LDL to oxidation was analyzed by incubation with CuSO4 and subsequent measurement of thiobarbituric acid reactive substance (TBARS) concentrations. Oral ERT significantly increased plasma triglyceride and decreased LDL diameter but did not affect LDL-derived TBARS concentrations. In contrast, transdermal ERT significantly decreased the concentrations of plasma triglyceride and LDL-derived TBARS and significantly increased LDL diameter. Estrogen-induced changes in LDL diameter correlated negatively with changes in plasma triglyceride (r=-0.51, P<0.001) and LDL-derived TBARS (r=-0.50, P<0.001).


CONCLUSIONS
Because transdermal, but not oral ERT, decreases plasma triglyceride and produces larger LDL particles that are resistant to oxidation, the antioxidant effect of estrogen can be preserved.
D000279:Administration, Cutaneous; D000284:Administration, Oral; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D019327:Copper Sulfate / Q000737:chemistry; D004717:Endometrium / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry*; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D010316:Particle Size; D017698:Postmenopause; D017392:Thiobarbituric Acid Reactive Substances / Q000737:chemistry; D014280:Triglycerides / Q000097:blood
D004966:Estrogens, Conjugated (USP); D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D004958:Estradiol; D019327:Copper Sulfate