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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #145028
Title: EFFECT OF HORMONAL REPLACEMENT THERAPY ON C-REACTIVE PROTEIN AND CELL-ADHESION MOLECULES IN POSTMENOPAUSAL MOLECULES IN POSTMENOPAUSAL WOMEN

Author
item LAMON-FAVA, STEFANIA - HNRCA
item POSFAI, BORBALA - NEMC
item SCHAEFER, ERNST - HNRCA

Submitted to: American Journal of Cardiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/9/2002
Publication Date: 3/1/2003
Citation: LAMON-FAVA, S., POSFAI, B., SCHAEFER, E.J. EFFECT OF HORMONAL REPLACEMENT THERAPY ON C-REACTIVE PROTEIN AND CELL-ADHESION MOLECULES IN POSTMENOPAUSAL MOLECULES IN POSTMENOPAUSAL WOMEN. AMERICAN JOURNAL OF CARDIOLOGY. 252-4,2003.

Interpretive Summary: Recent large clinical studies have suggested that hormonal replacement therapy (HRT) in postmenopausal women may increase the risk of cardiovascular disease by increasing inflammation and promoting thrombosis. We have assessed the effects of the two most commonly prescribed formulations of HRT, conjugated equine estrogen (CEE) alone and the combination of CEE with medroxyprogesterone acetate (CEE+MPA), on plasma levels of three inflammation markers in 14 healthy postmenopausal women. We found that plasma levels of C-reactive protein, a protein secreted by the liver, was increased approximately two-fold by both HRT regimens. In contrast, plasma levels of vascular cell adhesion molecule-1 (VCAM-1) and of intercellular adhesion molecule-1 (ICAM-1), proteins that are produced by vascular cells, were reduced by 7-8% during both treatments. We conclude that estrogen reduces that vascular markers of inflammation by increases C-reactive protein and that medroxyprogesterone acetate has no independent effect on these three markers of inflammation. The mechanism of these effects is not currently known.

Technical Abstract: The effects of two commonly prescribed formulations of hormonal replacement therapy (HRT) on inflammatory markers were assessed in a placebo-controlled, double-blind, randomized, crossover study consisting of three different phases, each lasting 8 weeks: 1) placebo, 2) conjugated equine estrogens (CEE, .625 mg/day), and 3) CEE (.625 mg/day) and medroxyprogesterone acetate (MPA, 2.5 mg/day). Phases were separated by 4 week washout periods. Fourteen postmenopausal women completed all three phases of the study. Plasma levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and of C-reactive protein (CRP) were measured during the three phases of the study. Plasma VCAM-1 and ICAM-1 levels were significantly lowered by treatment with CEE (-8.4%, and -8.4%, respectively, P<.01) and CEE and MPA (-6.4% and -7.6%, respectively, P<.05). Compared to placebo, treatment with CEE alone caused a 2-fold elevation in CRP levels (+105%, P<.0001) and treatment with the combination of CEE and MPA elevated CRP levels by 85% (P<.003). There was no significant independent effect of MPA on CRP levels. Therefore, estrogen replacement treatment has a differential effect on inflammatory markers by significantly reducing plasma levels of soluble adhesion molecules and increasing plama levels of CRP. Addition of 2.5 mg daily MPA to the estrogen regimen does not significantly affect the estrogen-mediated changes in these parameters.