Effect of lower dose of oral conjugated equine estrogen on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women.
BACKGROUND
Estrogen replacement therapy (ERT) has an antioxidant effect that opposes the oxidation of LDL. Oral ERT-induced increases in plasma triglyceride, however, are associated with decreased LDL size, which may counteract this antioxidant effect. Because lower doses of oral estrogen do not affect plasma triglyceride concentrations, LDL size might not change, and the antioxidant effect of estrogen might be preserved. We investigated whether a lower dose of oral estrogen could eliminate the adverse effects of high-dose oral ERT on the size and oxidative susceptibility of LDL in postmenopausal women.


RESULTS
Postmenopausal women received no treatment or were treated with oral conjugated equine estrogen (CEE) 0.625 or 0.3125 mg/d for 3 months. CEE at a dose of 0.625 mg/d significantly increased plasma triglyceride concentrations and decreased LDL diameter, but the concentrations of LDL-derived thiobarbituric acid reactive substances (TBARS) and lag time for conjugated diene formation did not change. In contrast, 0.3125 mg of CEE did not affect plasma triglyceride concentrations or LDL diameter and significantly decreased LDL-derived TBARS concentrations and significantly prolonged LDL lag time. Estrogen-induced changes in LDL diameter correlated negatively with changes in plasma triglyceride (r=-0.44, P<0.01) and LDL-derived TBARS (r=-0.57, P<0.001) but positively with changes in LDL lag time (r=0.42, P<0.01).


CONCLUSIONS
Because oral CEE at a dose of 0.3125 mg/d does not elevate plasma triglyceride, resulting in unchanged size of LDL particles that are resistant to oxidation, the antioxidant effect of estrogen can be preserved.
Wakatsuki
Akihiko
A
Department of Obstetrics and Gynecology, Kochi Medical School, Kochi, Japan 783-8505. wakatuki@kochi-ms.ac.jp
Okatani
Yuji
Y
Ikenoue
Nobuo
N
Shinohara
Koichi
K
Watanabe
Kazushi
K
Fukaya
Takao
T
D000284:Administration, Oral; D000975:Antioxidants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D007564:Japan; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry / Q000187:drug effects*; D008875:Middle Aged; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction / Q000187:drug effects; D010316:Particle Size; D017698:Postmenopause; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000975:Antioxidants; D004966:Estrogens, Conjugated (USP); D008077:Lipoproteins, LDL; D016877:Oxidants; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D004970:Estrone; D004958:Estradiol