This Article Full Text Full Text (PDF) All Versions of this Article: 26/2/385    most recent 01.ATV.0000199248.53590.e1v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lamon-Fava, S. Articles by Schaefer, E. J. Search for Related Content PubMed PubMed Citation Articles by Lamon-Fava, S. Articles by Schaefer, E. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ESTROGENIC SUBSTANCES, CONJUGATED

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:385.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Role of the Estrogen and Progestin in Hormonal Replacement Therapy on Apolipoprotein A-I Kinetics in Postmenopausal Women

Stefania Lamon-Fava; Borbala Postfai; Margaret Diffenderfer; Carl DeLuca; John O’Connor, Jr; Francine K. Welty; Gregory G. Dolnikowski; P. Hugh R. Barrett; Ernst J. Schaefer

From the Lipid Metabolism Laboratory (S.L.-F., B.P., M.D., C.D., J.O., E.J.S.), Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass; Division of Cardiology (F.K.W.), Beth Israel Deaconess Medical Center, Harvard University, Boston, Mass; the Mass Spectrometry Laboratory (G.G.D.), Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Mass; School of Medicine and Pharmacology (P.H.R.B.), University of Western Australia, Perth, Australia.

Correspondence to Stefania Lamon-Fava, Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research, Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111. E-mail stefania.lamon-fava{at}tufts.edu

Objective— Plasma high-density lipoprotein (HDL) cholesterol levels are inversely correlated with the risk of developing coronary heart disease. Hormonal replacement therapy (HRT) affects plasma HDL cholesterol levels, with estrogen increasing HDL cholesterol levels and progestins blunting this effect. This study was designed to assess the mechanism responsible for these effects.

Materials and Methods— HDL apolipoprotein A-I (apoA-I) kinetics were studied in 8 healthy postmenopausal women participating in a double-blind, randomized, crossover study comprising 3 phases: placebo, conjugated equine estrogen (CEE) (0.625 mg/d), and CEE plus medroxyprogesterone acetate (MPA) (2.5 mg/d). Compared with placebo, treatment with CEE resulted in an increase in apoA-I pool size (+20%, P<0.01) because of a significant increase in apoA-I production rate (+47%, P<0.05) and no significant changes in apoA-I fractional catabolic rate. Compared with the CEE alone phase, treatment with the CEE plus MPA resulted in an 8% (P<0.02) reduction in apoA-I pool size and a significant reduction in apoA-I production rate (–13%, P<0.04), without changes in apoA-I fractional catabolic rate.

Conclusion— Postmenopausal estrogen replacement increases apoA-I levels and production rate. When progestin is added to estrogen, it opposes these effects by reducing the production of apoA-I.

We studied the effect of estrogen and progestin in HRT on the metabolism of apoA-I in 8 postmenopausal women. Estrogen increased apoA-I levels and production rate, whereas the progestin counteracted the estrogen effect by reducing apoA-I levels and production rate.

Key Words: apolipoprotein A-I • estrogen • progestin • kinetics stable isotopes

This article has been cited by other articles:

				S. Lamon-Fava, M. R. Diffenderfer, P. H. R. Barrett, A. Buchsbaum, M. Nyaku, K. V. Horvath, B. F. Asztalos, S. Otokozawa, M. Ai, N. R. Matthan, et al. Extended-Release Niacin Alters the Metabolism of Plasma Apolipoprotein (Apo) A-I and ApoB-Containing Lipoproteins Arterioscler. Thromb. Vasc. Biol., September 1, 2008; 28(9): 1672 - 1678. [Abstract] [Full Text] [PDF]

				S. Lamon-Fava, M. R. Diffenderfer, P. H. R. Barrett, A. Buchsbaum, N. R. Matthan, A. H. Lichtenstein, G. G. Dolnikowski, K. Horvath, B. F. Asztalos, V. Zago, et al. Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism J. Lipid Res., August 1, 2007; 48(8): 1746 - 1753. [Abstract] [Full Text] [PDF]

				M. E. Wierman and W. M. Kohrt Review Article: Vascular and Metabolic Effects of Sex Steroids: New Insights Into Clinical Trials Reproductive Sciences, May 1, 2007; 14(4): 300 - 314. [Abstract] [PDF]

				S. Rashid, B. W. Patterson, and G. F. Lewis Thematic review series: Patient-Oriented Research. What have we learned about HDL metabolism from kinetics studies in humans? J. Lipid Res., August 1, 2006; 47(8): 1631 - 1642. [Abstract] [Full Text] [PDF]