CLINICAL STUDY: CARDIAC ISSUES IN WOMEN AND THE ELDERLY
Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women
Wanpen Vongpatanasin, MD, FACC*,*,
Meryem Tuncel, MD*,
Zhongyun Wang, MD*,
Debbie Arbique, RN*,
Borna Mehrad, MD* and
Ishwarlal Jialal, MD, PhD
* Donald W. Reynolds Cardiovascular Clinical Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, University of California at Davis Medical Center, Sacramento, California, USA
Manuscript received August 12, 2002;
revised manuscript received November 25, 2002,
accepted December 26, 2002.
* Reprint requests and correspondence: Dr. Wanpen Vongpatanasin, Divisions of Hypertension and Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, J4.134, Dallas, Texas 75390-8586, USA.
wanpen.vongpatanasin{at}utsouthwestern.edu
OBJECTIVES: We investigated whether the route of estrogen replacement therapy (ET) is the major determinant of C-reactive protein (CRP) in postmenopausal women.
BACKGROUND: Recent studies demonstrated that oral ET causes a sustained increase in CRP, implicating a proinflammatory effect. Because CRP is synthesized in the liver, we hypothesized that estrogen-induced CRP elevation is related to first-pass hepatic metabolism.
METHODS: In 21 postmenopausal women, we conducted a randomized, crossover, placebo-controlled study to compare the effects of transdermal versus oral ET on CRP and inflammatory cytokines. We measured CRP, interleukin (IL)-1-beta, IL-6, and tumor necrosis factor-alpha before and after eight weeks of transdermal estradiol (E2) (100 µg/day), oral conjugated estrogen (CEE) (0.625 mg/day), or placebo. Insulin-like growth factor-1 (IGF-1), a hepatic-derived anabolic peptide, was also measured.
RESULTS: Transdermal E2 had no effect on CRP or IGF-1 levels. In contrast, eight weeks of oral conjugated estrogens caused a more than twofold increase in CRP and a significant reduction in IGF-1 (p < 0.01) in the same women. The magnitude of increase in CRP was inversely correlated to the decrease in IGF-1 (r = –0.49, p = 0.008). Neither transdermal E2 nor oral CEE had any effects on the plasma concentrations of cytokines that promote CRP synthesis.
CONCLUSIONS: In postmenopausal women, oral but not transdermal ET increased CRP by a first-pass hepatic effect. An increase in CRP levels is accompanied by a reduction in IGF-1, an anti-inflammatory growth factor. Because CRP is a powerful predictor of an adverse prognosis in otherwise healthy postmenopausal women, the route of administration may be an important consideration in minimizing the adverse effects of ET on cardiovascular outcomes.
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Abbreviations and Acronyms
| | ET | | estrogen replacement therapy | | CEE | | conjugated equine estrogen | | HT | | combined hormone replacement therapy | | CRP | | C-reactive protein | | E2 | | estradiol | | hs-CRP | | highly sensitive C-reactive protein | | IGF-1 | | insulin-like growth factor-1 | | IL | | interleukin | | TNF-alpha | | tumor necrosis factor-alpha |
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