title: Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins.
abstract: The role of hormone replacement therapy and estrogen replacement therapy (ERT) in cardiovascular disease prevention has not been unambiguously defined yet. The metabolic effects of estrogens may vary depending upon the route of administration. Therefore, we compared the impact of unopposed oral or transdermal ERT on plasma lipids and lipoproteins in 41 hysterectomized women. This was an open-label, randomized, crossover study (with 2 treatments and 2 periods). The 41 hysterectomized women were randomized to receive oral or transdermal 17beta-estradiol in the first or second of two 12-week study periods. Plasma lipid and lipoprotein levels were assayed before and after each treatment using standard automated methods. Lipid content of lipoprotein subclasses was assessed by sequential ultracentrifugation. The atherogenic index of plasma (AIP) was calculated as log(triglyceride [TG]/high-density lipoprotein [HDL] cholesterol). The difference between the 2 forms of administration was tested using a linear mixed model. The change from baseline for each of the forms was tested using paired t test. Oral ERT resulted in a significant increase in HDL cholesterol and apolipoprotein A-I levels, whereas it significantly decreased total and low-density lipoprotein (LDL) cholesterol and increased TG concentrations. Transdermal ERT had no such effect. Oral ERT led to a significant TG enrichment of HDL (0.19 +/- 0.06 vs 0.27 +/- 0.07 mmol/L, P < .001) and LDL particles (0.23 +/- 0.08 vs 0.26 +/- 0.10 mmol/L, P < .001) compared with baseline, whereas transdermal therapy did not have any effect on lipoprotein subclasses composition. The difference between the 2 treatments was statistically significant for HDL-TG and LDL-TG (0.27 +/- 0.07 vs 0.19 +/- 0.05 mmol/L, P < .001 and 0.26 +/- 0.10 vs 0.22 +/- 0.07 mmol/L, P< .001, respectively). The transdermal but not oral ERT significantly reduced the AIP compared with baseline (-0.17 +/- 0.26 vs -0.23 +/- 0.25, P = .023), making the difference between the therapies statistically significant (-0.23 +/- 0.25 vs -0.18 +/- 0.22, P = .017). Oral administration of ERT resulted in TG enrichment of LDL and HDL particles. Transdermal ERT did not change the composition of the lipoproteins and produced a significant improvement of AIP. Compared with transdermal ERT, orally administered ERT changes negatively the composition of plasma lipoproteins.
authors.affiliation: 3rd Department of Internal Medicine, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. vrablikm@seznam.cz
authors.forename: Michal
authors.initials: M
authors.lastname: Vrablik
authors.forename: Tomas
authors.initials: T
authors.lastname: Fait
authors.forename: Jan
authors.initials: J
authors.lastname: Kovar
authors.forename: Rudolf
authors.initials: R
authors.lastname: Poledne
authors.forename: Richard
authors.initials: R
authors.lastname: Ceska
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008074:Lipoproteins / Q000097:blood*; D008875:Middle Aged; D010052:Ovariectomy; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D014280:Triglycerides; D004958:Estradiol