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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #191686
Title: ROLE OF ESTROGEN AND PROGESTIN IN HORMONAL REPLACEMENT THERAPY ON APOLIPOPROTEIN A-1 KINETICS IN POSTMENOPAUSAL WOMEN

Author
item Lamon-Fava, Stefania
item POSTFAI, BORBALA - TUFTS UNIVERSITY
item DELUCA, CARL - TUFTS UNIVERSITY
item DIFFERENDERFER, MARGARET - TUFTS/HNRCA
item O'CONNER, JOHN - TUFTS UNIVERSITY
item WELTY, FRANCIS - HARVARD UNIVERSITY
item Dolnikowski, Gregory
item BARRETT, P HUGH - UNIV OF WESTERN AUSTRALIA
item Schaefer, Ernst

Submitted to: Arteriosclerosis Thrombosis and Vascular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/28/2005
Publication Date: 2/1/2006
Citation: Lamon-Fava, S., Postfai, B., Deluca, C., Differenderfer, M., O'Conner, J., Welty, F.K., Dolnikowski, G., Barrett, P.R., Schaefer, E. 2006. Role of estrogen and progestin in hormonal replacement therapy on apolipoprotein a-1 kinetics in postmenopausal women. Arterioscler Thrombosis and Vascular Biology. 26(2):385-91. Epub 2005 Dec 8.

Interpretive Summary: Postmenopausal hormonal replacement therapy (HRT) has been shown to affect plasma levels of HDL cholesterol, or "good cholesterol." The estrogen component of HRT causes an increase in HDL, and the progestin component blunts the estrogen effect. We studied the in vivo mechanisms of the effects of estrogen and progestin on HDL cholesterol levels by studying the rate of production and clearance of apoA-I, the major protein component of HDL, in 8 postmenopausal women. Our study indicates the treatment with only estrogen causes a 20% increase in plasma apoA-I levels, which is due to a 47% increase in the production of apoA-I. When progestin is added to the estrogen replacement, a reduction (-8%) in plasma apoA-I levels is observed, and this is due to a reduction in apoA-I production (-13%). Our data indicate that adding progestin to estrogen replacement reduces the beneficial effect on HDL levels.

Technical Abstract: High-density lipoprotein (HDL) cholesterol levels are inversely correlated with the risk of developing coronary heart disease. Hormonal replacement therapy (HRT) affects HDL cholesterol levels, with estrogen increasing plasma HDL cholesterol levels and progestins blunting this effect. This study was designed to assess the mechanisms responsible for these effects. HDL apolipoprotein A-I (apo A-I) kinetics were studied in 8 healthy postmenopausal women participating in a double blind, randomized, crossover study compromising three phases: placebo, conjugated equine estrogen (CEE, 0.625 mg/day), and CEE plus medroxyprogesterone acetate (MPS, 2.5 mg/day). Compared with placebo, treatment with CEE resulted in an increase in apoA-I pool size (+20%, P<0.01) due to a significant increase in apoA-I production rate (+47%, P<0.05) and no significant changes in apoA-I fractional catabolic rate. Compared with CEE phase, treatment with CEE plus MPA resulted in an 80% (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. Estrogen replacement increases apoA-I production rate, while the progestin component in HRT has an opposite effect by reducing the production of apoA-I.