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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1666.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Lipoprotein Particle Concentrations May Explain the Absence of Coronary Protection in the Women’s Health Initiative Hormone Trials

Judith Hsia; James D. Otvos; Jacques E. Rossouw; LieLing Wu; Sylvia Wassertheil-Smoller; Susan L. Hendrix; Jennifer G. Robinson; Bernedine Lund; Lewis H. Kuller for the Women’s Health Initiative Research Group

From the Department of Medicine (J.H.), George Washington University, Washington, DC; Liposcience Inc (J.D.O.), Raleigh, NC; National Heart, Lung, and Blood Institute (J.R.), National Institutes of Health, Bethesda, Md; Fred Hutchinson Cancer Research Center (L.W., B.L.), Seattle, Wash; the Department of Epidemiology & Social Medicine (S.S.), Albert Einstein College of Medicine, Bronx, NY; the Department of Obstetrics and Gynecology (S.L.H.), Detroit Medical Center, Detroit, Mich; the Department of Medicine (J.G.R.), University of Iowa, Iowa City; and the Department of Epidemiology (L.H.K.), University of Pittsburgh, Pa.

Correspondence to Dr Judith Hsia, AstraZeneca LP, 1800 Concord Pike, Room C3C-123, PO Box 15437, Wilmington, DE 19850-5437. E-mail judith.hsia{at}astrazeneca.com

Objective— The Women’s Health Initiative randomized hormone trials unexpectedly demonstrated an increase in early coronary events. In an effort to explain this finding, we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case–control substudy.

Methods and Results— We randomized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10 739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo, and measured lipoprotein subclasses by nuclear magnetic resonance spectroscopy at baseline and year 1 in 354 women with early coronary events and matched controls. Postmenopausal hormone therapy raised high-density lipoprotein cholesterol and particle concentration and reduced low-density lipoprotein cholesterol (LDL-C; all P<0.001 versus placebo). In contrast, neither unopposed estrogen nor estrogen with progestin lowered low-density lipoprotein particle concentration (LDL-P).

Conclusions— Postmenopausal hormone therapy–induced reductions in LDL-C were not paralleled by favorable effects on LDL-P. This finding may account for the absence of coronary protection conferred by estrogen in the randomized hormone trials.

In the Women’s Health Initiative randomized trials, postmenopausal hormone therapy raised high density lipoprotein-cholesterol and particle concentration and reduced low density lipoprotein-cholesterol (P<0.001 versus placebo). Neither unopposed estrogen nor estrogen with progestin lowered low density lipoprotein particle concentration.

Key Words: lipoproteins • estrogen • women • coronary heart disease

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