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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:1101.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Mechanisms Regulating LDL Metabolism in Subjects on Peroral and Transdermal Estrogen Replacement Therapy

Anna Karjalainen; Jorma Heikkinen; Markku J. Savolainen; Ann-Christine Bäckström; Y. Antero Kesäniemi

From the Department of Internal Medicine and Biocenter Oulu (A.K., M.J.S., Y.A.K.), University of Oulu, and the Oulu Deaconess Institute (J.H.), Oulu, Finland, and the Orion Corp, Orion Pharma (A.-C.B.), Espoo, Finland.

Correspondence to Prof Y. Antero Kesäniemi, MD, PhD, Department of Internal Medicine, University of Oulu, Kajaanintie 50, 90220 Oulu, Finland. E-mail antero.kesaniemi{at}oulu.fi

Abstract—To study the mechanisms of low density lipoprotein (LDL) cholesterol lowering by peroral and transdermal estrogen replacement therapy (ERT), 79 hysterectomized postmenopausal women aged 48 to 62 years were randomized in a double-blind double-dummy trial to receive either peroral estradiol valerate (2 mg/d) or transdermal estradiol gel (1 mg/d) for 6 months. Plasma LDL cholesterol decreased from 4.19±0.83 (mean±SD) to 3.39±0.78 mmol/L (P<0.001) in the peroral group and from 4.11±0.86 to 3.72±0.78 mmol/L (P<0.001) in the transdermal estrogen group. Peroral estrogen did, but transdermal treatment did not, enhance the fractional catabolic rate (FCR) and production of LDL apolipoprotein B (apoB). However, the decrease of LDL cholesterol was related to an increase in FCR for LDL apoB on both peroral and transdermal ERT (r=-0.645, P<0.001 and r=-0.627, P<0.001, respectively). These changes were associated with changes in the serum estrogen level. Both therapies reduced absorption of dietary cholesterol by 6% to 10% (P<0.05). The effects of estrogen were not modified by the polymorphisms of apoE and apoB or cholesterol 7-hydroxylase. In conclusion, the ERT-induced LDL cholesterol–lowering effect is related to changes in estrogen level, which presumably enhance LDL receptor activity, which is manifested as an increase in FCR for LDL apoB. The small decrease in the absorption efficiency of dietary cholesterol does not seem to contribute largely to the cholesterol lowering on either transdermal or peroral ERT.

Key Words: estrogen replacement therapy • LDL cholesterol • menopause • lipids

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