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Circulation. 1998;97:979-986

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(Circulation. 1998;97:979-986.)
© 1998 American Heart Association, Inc.


Clinical Investigation and Reports

Effect of Postmenopausal Hormone Therapy on Lipoprotein(a) Concentration

Mark A. Espeland, PhD; Santica M. Marcovina, PhD, ScD; Valery Miller, MD; Peter D. Wood, DSc; Carol Wasilauskas, MS; Roger Sherwin, MB; BChir; Helmut Schrott, MD; Trudy L. Bush, PhD; ; for the PEPI Investigators

From the Section on Biostatistics, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (M.A.E, C.W.); the Department of Medicine, University of Washington, Northwest Lipid Research Laboratories, Seattle (S.M.M); George Washington University Lipid Research Clinic, Washington, DC (V.M.); the Center for Research in Disease Prevention, Stanford University, Palo Alto, Calif (P.D.W.); the Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore (T.L.B., R.S.); and the Lipid Research Clinic, University of Iowa, Iowa City (H.S.).

Correspondence to Mark A. Espeland, PhD, Section on Biostatistics, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1063. E-mail mespelan{at}rc.phs.bgsm.edu

Background—Postmenopausal hormone therapy has been reported to decrease levels of lipoprotein (Lp)(a) in cross-sectional studies and small or short-term longitudinal studies. We report findings from a large, prospective, placebo-controlled clinical trial that allows a broad characterization of these effects for four regimens of hormone therapy.

Methods and Results—The Postmenopausal Estrogen/Progestin Interventions study was a 3-year, placebo-controlled, randomized clinical trial to assess the effect of hormone regimens on cardiovascular disease risk factors in postmenopausal women 45 to 65 years of age. The active regimens were conjugated equine estrogens therapy at 0.625 mg daily, alone or in combination with each of three regimens of progestational agents: medroxyprogesterone acetate (MPA) at 2.5 mg daily (ie, continuous MPA), MPA at 10 mg days 1 to 12 (ie, cyclical MPA), and micronized progesterone at 200 mg days 1 to 12. Plasma levels of Lp(a) were measured at baseline (n=366), 12 months (n=354), and 36 months (n=342). Assignment to hormone therapy resulted in a 17% to 23% average drop in Lp(a) concentrations relative to placebo (P<.0001), which was maintained across 3 years of follow-up. No significant differences were observed among the four active arms. Changes in Lp(a) associated with hormone therapy were positively correlated with changes in LDL cholesterol, total cholesterol, apolipoprotein B, and fibrinogen levels and were similar across subgroups defined by age, weight, ethnicity, and prior hormone use.

Conclusions—Postmenopausal estrogen therapy, with or without concomitant progestin regimens, produces consistent and sustained reductions in plasma Lp(a) concentrations.


Key Words: lipids • lipoproteins • hormones • cardiovascular diseases • risk factors




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