Different Effects of Oral and Transdermal Hormone Replacement Therapies on Factor IX, APC Resistance, t-PA, PAI and C-reactive Protein

Gordon D. O. Lowe; Mark N. Upton; Ann Rumley; Alex McConnachie; Denis St. J. O’Reilly; Graham C. M. Watt

doi:10.1055/s-0037-1616085

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2001; 86(02): 550-556
DOI: 10.1055/s-0037-1616085

Review Article

Schattauer GmbH

Different Effects of Oral and Transdermal Hormone Replacement Therapies on Factor IX, APC Resistance, t-PA, PAI and C-reactive Protein

A Cross-sectional Population Survey

Gordon D. O. Lowe

¹From the University Department of Medicine, Glasgow Royal Infirmary, Department of General Practice, University of Glasgow

,

Mark N. Upton

¹From the University Department of Medicine, Glasgow Royal Infirmary, Department of General Practice, University of Glasgow

,

Ann Rumley

¹From the University Department of Medicine, Glasgow Royal Infirmary, Department of General Practice, University of Glasgow

,

Alex McConnachie

¹From the University Department of Medicine, Glasgow Royal Infirmary, Department of General Practice, University of Glasgow

,

Denis St. J. O’Reilly

²Institute of Biochemistry, Glasgow Royal Infirmary, Glasgow, UK

,

Graham C. M. Watt

¹From the University Department of Medicine, Glasgow Royal Infirmary, Department of General Practice, University of Glasgow

› Institutsangaben

Abstract

Summary

The effects of hormone replacement therapy (HRT) on thrombosis risk, thrombotic variables, and the inflammatory marker C-reactive protein (CRP) may vary by route of administration (oral versus transdermal). We studied the relationships of 14 thrombotic variables (previously related to cardiovascular risk) and CRP to menopausal status and to use of HRT subtypes in a cross-sectional study of 975 women aged 40-59 years. Our study confirmed previously-reported associations between thrombotic variables and menopausal status. Oral HRT use was associated with increased plasma levels of Factor IX, activated protein C (APC) resistance, and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity. Factor VII levels were higher in women taking unopposed oral oestrogen HRT. The foregoing associations were not observed in users of transdermal HRT; hence they may be consequences of the “first-pass” effect of oral oestrogens on hepatic protein synthesis. We conclude that different effects of oral and transdermal HRT on thrombotic and inflammatory variables may be relevant to their relative thrombotic risk; and suggest that this hypothesis should be tested in prospective, randomised studies.

Keywords

Oestrogens - menopause - C-reactive protein - coagulation - fibrinolysis

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References
1 Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in post-menopausal women. Prog Cardiovasc Dis 1995; 38: 199-210.
2 Grodstein F, Stampfer MJ, Manson JE. et al. Post-menopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med 1996; 335: 453-61.
3 Chae CU, Ridker PM, Manson JE. Post-menopausal hormone replacement therapy and cardiovascular disease. Thromb Haemost 1997; 78: 770-80.
4 Meade TW. Hormone replacement therapy and haemostatic function. Thromb Haemost 1997; 78: 765-9.
5 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.
6 Jick H, Derby LE, Myers MW, Vasilakis C, Newton KM. Risk of hospital admission for idiopathic venous thromboembolism among users of post-menopausal oestrogens. Lancet 1996; 348: 981-3.
7 Grodstein F, Stampfer MJ, Goldhaber SZ. et al. Prospective study of exogenous hormones and risk of pulmonary embolism in women. Lancet 1996; 348: 983-7.
8 Gutthann SP, Rodriguez LAG, Castellague J. Hormone replacement therapy and risk of venous thromboembolism: population based case-control study. BMJ 1997; 314: 796-800.
9 Varas-Lorenzo C, Garcia-Rodriguez LA, Cattaruzzi C. Hormone replacement therapy and the risk of hospitalization for venous thromboembolism: a population-based study in Southern Europe. Am J Epidemiol 1998; 147: 387-90.
10 Grady D, Wenger NK, Herrington D, Khan S, Furberg C, Hunningkate D, Vittinghoff E, Hulley S. Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Ann Intern Med 2000; 132: 689-96.
11 Lowe GDO, Rumley A, Woodward M, Reid E, Rumley J. Activated protein C resistance and the FV: R506Q mutation in a random population sample. Thromb Haemost 1999; 81: 918-24.
12 Crook D. The metabolic consequences of treating post-menopausal women with non-oral hormone replacement therapy. Br J Obstet Gynaecol 1997; 104 (Suppl. 16) 4-13.
13 Koh KK, Mincemoyer R, Bui MN. et al. Effects of hormone-replacement therapy on fibrinolysis in post-menopausal women. N Engl J Med 1997; 336: 683-90.
14 Scarabin P-Y, Alhenc-Gelas M, Pluc-Bureau G, Taisne P, Agher R, Aiach M. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in post-menopausal women. Arterioscler Thromb Vasc Biol 1997; 17: 3071-8.
15 Lowe GDO. Haemostatic risk factors for arterial and venous thrombosis. In: Poller L, Ludlam CA. (eds). Recent Advances in Blood Coagulation, 7. Edinburgh: Churchill Livingstone; 1997: 69-96.
16 Upton MN, McConnachie A, McSharry C, Hart CL, Davey Smith G, Gillis CR, Watt GCM. Intergenerational 20 year trends in the prevalence of asthma and hay fever in adults-the Midspan family study surveys of parents and offspring. BMJ 2000; 321: 88-92.
17 Rosenson RS, Lowe GDO. Effects of lipids and lipoproteins on thrombosis and rheology. Atherosclerosis 1998; 140: 271-80.
18 Mitropoulis KA. Lipid-thrombosis interface. Br Med Bull 1996; 50: 813-52.
19 Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. Meta-analyses of prospective studies. JAMA 1998; 279: 1477-82.
20 Hawthorne VM, Watt GCM, Hart CL, Davey Smith G, Gillies CR. Cardio-respiratory disease in men and women in urban Scotland: baseline characteristics of the Renfrew/Paisley (Midspan) study population. Scot Med J 1995; 40: 102-7.
21 Woodward M, Rumley A, Tunstall-Pedoe H, Lowe GDO. Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease. Br J Haematol 1999; 104: 246-57.
22 Lowe GDO, Rumley A, Woodward M, Morrison CE, Philippou H, Lane DA, Tunstall-Pedoe H. Epidemiology of coagulation factors, inhibitors and activation markers: The Third Glasgow MONICA Survey. I. Illustrative reference ranges by age, sex and hormone use. Br J Haematol 1997; 97: 775-84.
23 Lowe GDO, Yarnell JWG, Sweetnam PM, Rumley A, Thomas HF, Elwood PC. Fibrin D-dimer, tissue plasminogen activator, plasminogen activator inhibitor, and the risk of major ischaemic heart disease in the Caerphilly Study. Thromb Haemost 1998; 79: 129-33.
24 Smith FB, Lee AJ, Fowkes FGR, Price JF, Rumley A, Lowe GDO. Haemostatic factors as predictors of ischaemic heart disease and stroke in the Edinburgh Artery Study. Arterioscler Thromb Vasc Biol 1997; 17: 3321-5.
25 Lowe GDO, Woodward M, Vessey MP, Rumley A, Gough P, Daly E. Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45-64 years: relationships to hormone replacement therapy. Thromb Haemost 2000; 83: 530-5.
26 Frohlich M, Schunkert H, Hense HW, Tropitzsch A, Hendricks P, Doring A, Riegger GAJ, Koenig W. Effects of hormone replacement therapies on fibrinogen and plasma viscosity in postmenopausal women. Br J Haematol 1998; 100: 577-81.
27 Nabulsi AA, Folsom AAR, White A, Patsh W, Heiss G, Wu KK, Szklo M. Association of hormone-replacement therapy with various cardiovascular risk factors in postmenopausal women. N Engl J Med 1993; 328: 1069-75.
28 Medical Research Council’s General Practice Research Framework.. Randomised comparison of oestrogen versus oestrogen plus progestogen hormone replacement therapy in women with hysterectomy. BMJ 1996; 312: 473-8.
29 Lowe GDO. Coagulation, fibrinolysis and hormone replacement therapy. In: Shaw RW. (ed). Oestrogen Deficiency, Causes and Consequences. Advances in Reproductive Endocrinology. Volume 8. Carnforth: Parthenon; 1996: 29-43.
30 De Mitrio V, Marino R, Cicirelli E. et al. Beneficial effects of postmenopausal hormone replacement therapy with transdermal estradiol on sensitivity to activated protein C. Blood Coagul Fibrinolys 2000; 11: 175-82.
31 Shahar E, Folsom AR, Salomaa VV, Stinson VL, McGovern PG, Shimakawa T, Chambless LE, Wu KK. Relation of hormone replacement therapy to measures of plasma fibrinolytic activity. Circulation 1996; 93: 1970-5.
32 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.
33 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.
34 Zuckerman SH, Ahmari SE, Bryan-Poole N, Evans GF, Short L, Glase-brook AL. Estriol: a potent regulator of TNF and IL-6 expression in a murine model of endotoxemia. Inflammation 1996; 20: 581-97.
35 Walker FJ, Fay PJ. Characterization of an interaction between protein C and ceruloplasmin. J Biol Chem 1990; 265: 1834-6.
36 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.
37 Ridker PM, Buring JE, Shin 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.
38 Danesh J, Collins R, Peto R, Lowe GDO. Haematocrit, viscosity, erythrocyte sedimentation rate: meta-analyses of prospective studies of coronary heart disease. Europ Heart J 2000; 21: 515-20.