Download PDF
Thromb Haemost 2002; 88(04): 605-610
DOI: 10.1055/s-0037-1613263
Review Article
Schattauer GmbH

Effects of Transdermal and Oral Oestrogen Replacement Therapy on C-Reactive Protein Levels in Postmenopausal Women: A Randomised, Placebo-Controlled Trial

M. S. Post
1   Project “Ageing Women” and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Departments of Obstetrics and Gynaecology
,
M. J. van der Mooren
1   Project “Ageing Women” and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Departments of Obstetrics and Gynaecology
,
C. D. A. Stehouwer
2   Internal Medicine
,
W. M. van Baal
1   Project “Ageing Women” and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Departments of Obstetrics and Gynaecology
,
V. Mijatovic
1   Project “Ageing Women” and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Departments of Obstetrics and Gynaecology
,
C. G. Schalkwijk
3   Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
,
P. Kenemans
1   Project “Ageing Women” and the Institute for Cardiovascular Research-Vrije Universiteit (ICaR-VU), Departments of Obstetrics and Gynaecology
› Author AffiliationsThis work was supported by research grants from the Netherlands Heart Foundation (grant 95.201), Biocare Foundation (grant 96.312), and Schering AG (Berlin, Germany, grant 96.083)
Further Information

Publication History

Received 21 January 2002

Accepted after resubmission 26 June 2002

Publication Date:
09 December 2017 (online)

    Permissions and Reprints

Summary

To investigate the effect of postmenopausal oral and transdermal hormone therapy on plasma levels of C-reactive protein (CRP), we performed a randomised, double-blind, double-dummy, placebo-controlled, 15-month study. One hundred and fifty-two healthy hysterectomised postmenopausal women received daily either placebo (n = 49), or transdermal 17 β-oestradiol (E2) 50 µg (tE2 group, n = 33), or oral E2 1 mg (oE2 group, n = 37), or oral E2 1 mg combined with gestodene 25 µg (oE2 + G group, n = 33) for thirteen 28-day treatment cycles, followed by four cycles placebo for each group. Data were collected at baseline and in cycles 4, 13 and 17. In cycle 13, CRP was significantly increased in the oE2 group compared to placebo (P = 0.004). The median percentage change from baseline versus placebo was +75% (P <0.001). In cycle 17, significantly lower values were observed in the oE2 group compared to cycle 13 and to the placebo group (-49%, P <0.001). There were no significant changes versus placebo in the other groups. In conclusion, oral E2 significantly increased CRP levels. This change was larger than the increase found during oral E2 + G. Transdermal E2 did not affect CRP levels.

Keywords

C-reactive protein - postmenopausal - hormone replacement therapy - oestrogen - gestodene
 

  • References

  • 1 Ross R. Atherosclerosis an inflammatory disease. N Engl J Med 1999; 340: 115-26.
    CrossrefPubMedGoogle Scholar
  • 2 Ridker PM, Cushman M, Stampfer MJ, Tracy RM, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973-9.
    CrossrefPubMedGoogle Scholar
  • 3 Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998; 98: 731-3.
    CrossrefPubMedGoogle Scholar
  • 4 Koenig W, Sund M, Fröhlich M, Fischer HG, Lowel H, Döring A, Hutchinson WL, Pepys MB. C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999; 99: 237-42.
    CrossrefPubMedGoogle Scholar
  • 5 Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836-43.
    CrossrefPubMedGoogle Scholar
  • 6 Strandberg TE, Tilvis RS. C-reactive protein, cardiovascular risk factors, and mortality in a prospective study in the elderly. Arterioscler Thromb Vasc Biol 2000; 20: 1057-60.
    CrossrefPubMedGoogle Scholar
  • 7 Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet 1997; 349: 462-6.
    CrossrefPubMedGoogle Scholar
  • 8 Lagrand WK, Niessen HW, Wolbink GJ, Jaspars LH, Visser CA, Verheugt FW, Meijer CJ, Hack CE. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation 1997; 95: 97-103.
    CrossrefPubMedGoogle Scholar
  • 9 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102: 2165-8.
    CrossrefPubMedGoogle Scholar
  • 10 Hulley S, Grady D, Bush T, Furberg C, Herrington D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. JAMA 1998; 280: 605-13.
    CrossrefPubMedGoogle Scholar
  • 11 Van Baal WM, Kenemans P, van der Mooren MJ, Kessel H, Emeis JJ, Stehouwer CDA. Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women. Thromb Haemost 1999; 81: 925-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 De Valk-de Roo GW, Stehouwer CDA, Meijer P, Mijatovic V, Kluft C, Kenemans P, Cohen F, Watts S, Netelenbos C. Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women: A 2-year, placebo-controlled study. Arterioscler Thromb Vasc Biol 1999; 19: 2993-3000.
    CrossrefPubMedGoogle Scholar
  • 13 Cushman M, Meilahn EN, Psaty BM, Kuller LH, Dobs AS, Tracy RP. Hormone replacement therapy, inflammation, and hemostasis in elderly women. Arterioscler Thromb Vasc Biol 1999; 19: 893-9.
    CrossrefPubMedGoogle Scholar
  • 14 Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JE. Hormone replacement therapy and increased plasma concentration of Creactive protein. Circulation 1999; 100: 713-6.
    CrossrefPubMedGoogle Scholar
  • 15 Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, Judd HL, Sakkinen PA, Tracy RP. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation 1999; 100: 717-22.
    CrossrefPubMedGoogle Scholar
  • 16 Lowe G, Rumley A, Woodward M, Vessey M. C-reactive protein, idiopathic venous thromboembolism and hormone replacement therapy. Thromb Haemost 2000; 84: 730-1.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Walsh BW, Paul S, Wild RA, Dean RA, Tracy RP, Cox DA, Anderson PW. The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab 2000; 85: 214-8.
    PubMedGoogle Scholar
  • 18 Barinas-Mitchell E, Cushman M, Meilahn EN, Tracy RP, Kuller LH. Serum levels of C-reactive protein are associated with obesity, weight gain, and hormone replacement therapy in healthy postmenopausal women. Am J Epidemiol 2001; 153: 1094-101.
    CrossrefPubMedGoogle Scholar
  • 19 Lowe GDO, Upton MN, Rumley A, McConnachie A, O’Reilly DStJ, Watt GCM. Different effects of oral and transdermal hormone replacement therapies on factor IX, APC resistance, t-PA, PAI and C-reactive protein. Thromb Haemost 2001; 86: 550-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Vehkavaara S, Silveira A, Hakala-Ala-Pietila T, Virkamaki A, Hovatta O, Hamsten A, Taskinen MR, Yki-Jarvinen H. Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. Thromb Haemost 2001; 85: 619-25.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 21 Luyer MD, Khosla S, Owen WG, Miller VM. Prospective randomized study of effects of unopposed estrogen replacement therapy on markers of coagulation and inflammation in postmenopausal women. J Clin Endocrinol Metab 2001; 86: 3629-34.
    CrossrefPubMedGoogle Scholar
  • 22 Zanger D, Yang BK, Ardans J, Waclawiw MA, Csako G, Wahl LM, Cannon RO. Divergent effects of hormone therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management. J Am Coll Cardiol 2000; 36: 1797-802.
    CrossrefPubMedGoogle Scholar
  • 23 Oger E, Alhenc-Gelas M, Plu-Bureau G, Mennen L, Cambillau M, Guize L, Pujol Y, Scarabin P. Association of circulating cellular adhesion molecules with menopausal status and hormone replacement therapy Time-dependent change in transdermal, but not oral estrogen users. Thromb Res 2001; 101: 35-43.
    CrossrefPubMedGoogle Scholar
  • 24 Kamphuisen PW, Eikenboom JC, Vos HL, Pablo R, Sturk A, Bertina RM, Rosendaal FR. Increased levels of factor VIII and fibrinogen in patients with venous thrombosis are not caused by acute phase reactions. Thromb Haemost 1999; 81: 680-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Grodstein F, Stampfer MJ, Goldhaber SZ, Manson JE, Colditz GA, Speizer FE, Willett WC, Hennekens CH. Prospective study of exogenous hormones and risk of pulmonary embolism in women. Lancet 1996; 348: 983-7.
    CrossrefPubMedGoogle Scholar
  • 26 Daly E, Vessey MP, Hawkins MM, Carson JL, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 1996; 348: 977-80.
    CrossrefPubMedGoogle Scholar
  • 27 Jick H, Derby LE, Wald MMeyers, Vasilakis C, Newton KM. Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Lancet 1996; 348: 981-3.
    CrossrefPubMedGoogle Scholar
  • 28 Van Baal WM, Emeis JJ, Kenemans P, Kessel H, Peters-Muller ERA, Schalkwijk CG, van der Mooren MJ, Stehouwer CDA. Short-term hormone replacement therapy: reduced plasma levels of soluble adhesion molecules. Eur J Clin Invest 1999; 29: 913-21.
    CrossrefPubMedGoogle Scholar
  • 29 Sattar N, Perera M, Small M, Lumsden MA. Hormone replacement therapy and sensitive C-reactive protein concentrations in women with type-2 diabetes. Lancet 1999; 354: 487-8.
    CrossrefPubMedGoogle Scholar
  • 30 Giltay EJ, Gooren LJG, Emeis JJ, Kooistra T, Stehouwer CDA. Oral ethinyl estradiol, but not transdermal 17beta-estradiol, increases plasma C-reactive protein levels in men. Thromb Haemost 2000; 84: 359-60.
    Article in Thieme ConnectPubMedGoogle Scholar