TY - JOUR
T1 - Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women
AU - Vongpatanasin, Wanpen
AU - Tuncel, Meryem
AU - Wang, Zhongyun
AU - Arbique, Debbie
AU - Mehrad, Borna
AU - Jialal, Ishwarlal
N1 - Funding Information:
This study was supported by grant K23RR16321 to Dr. Vongpatanasin from the National Institutes of Health, Bethesda, Maryland; grant K24AT00596 to Dr. Jialal from the National Institutes of Health; and grant M01-RR00633 to the University of Texas Southwestern General Clinical Research Center Grant from the U.S. Public Health Service.
PY - 2003/4
Y1 - 2003/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037394565&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037394565&partnerID=8YFLogxK
U2 - 10.1016/S0735-1097(03)00156-6
DO - 10.1016/S0735-1097(03)00156-6
M3 - Article
C2 - 12706932
AN - SCOPUS:0037394565
SN - 0735-1097
VL - 41
SP - 1358
EP - 1363
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 8
ER -