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Long-term effects of combined hormone replacement therapy on markers of endothelial function and inflammatory activity in healthy postmenopausal women

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Author: Baal, W.M. van · Kenemans, P. · Emeis, J.J. · Schalkwijk, C.G. · Mijatovic, V. · Mooren, M.J. van der · Vischer, U.M. · Stehouwer, C.D.A.
Type:article
Date:1999
Institution: Gaubius instituut TNO
Source:Fertility and Sterility, 4, 71, 663-670
Identifier: 234994
doi: doi:10.1016/S0015-0282(98)00513-5
Keywords: Health · E- selectin · Endothelial function · Endothelin-1 · Estrogen · Fibrinogen · Hormone replacement therapy · Inflammatory activity · Postmenopausal · Thrombomodulin · Von Willebrand factor · C reactive protein · Dydrogesterone · E-Selectin · Endothelin-1 · Endothelium, Vascular · Estradiol · Estrogen Replacement Therapy · Female · Fibrinogen · Humans · Inflammation · Middle Aged · Postmenopause · Prospective Studies · Solubility · Thrombomodulin · von Willebrand Factor

Abstract

Objective: To study the effects of combined hormone replacement therapy on markers of endothelial function and inflammatory activity. Design: Prospective, randomized, controlled study. Setting: Academic hospital. Patient(s): Healthy postmenopausal women with an intact uterus. Intervention(s): For the first 12 months, the hormone replacement therapy group (n = 14) received oral E2, 1 mg daily, sequentially combined with 5 or 10 mg of dydrogesterone. Thereafter, they received oral E2, 2 mg daily, sequentially combined with 10 mg of dydrogesterone. The control group (n = 13) received no treatment. Data were collected at baseline and at 3, 12, and 15 months. Main Outcome Measure(s): Parameters of endothelial function and inflammatory activity. Result(s): During 12 months of follow-up, we observed decreases of 15% in plasma levels of endothelin-1, of 21% in soluble thrombomodulin, of 14% in von Willebrand factor, and of 12% in clottable fibrinogen in the hormone replacement therapy group compared with the control group. There was a 5% decrease in soluble E-selectin levels. All significant changes were observed by 3 months and sustained after 15 months. Brachial artery flow-mediated vasodilatation and C-reactive protein levels did not change significantly. Conclusion(s): Long-term combined hormone replacement therapy with E2 and dydrogesterone in healthy women was associated with sustained improvement in some aspects of endothelial function and in clottable fibrinogen levels.