European Journal of Epidemiology

, Volume 20, Issue 12, pp 1015–1022 | Cite as

Association of Endogenous Hormones with C-reactive Protein, Fibrinogen, and White Blood Count in Post-menopausal Women

  • Aaron R. Folsom
  • Sherita Hill Golden
  • Lori L. Boland
  • Moyses Szklo
Endocrine Epidemiology


Oral exogenous estrogen raises C-reactive protein (CRP) concentrations, but the impact of endogenous hormones is unknown. We examined the cross-sectional relation of several serum hormones with CRP, fibrinogen, and white blood cell count – three inflammatory markers linked prospectively to coronary artery disease. Serum hormones were measured on a sample (n=317) of postmenopausal female participants, with or without carotid intima-media thickening, in the Atherosclerosis Risk in Communities (ARIC) Study. Fibrinogen and white blood cell count were available on all and CRP in a subset (n=57). Adjusted for age, race, and case-control status, mean CRP was 2-fold greater in the highest vs. lowest quartiles of estrone and androstenedione, and CRP was 2-fold less across quartiles of sex hormone binding globulin. These associations were not all statistically significant with this sample size. Fibrinogen and white blood cell count also were associated positively with estrone, androstenedione, and testosterone (and fibrinogen also with dehydroepiandrosterone sulfate). Adjustment for other risk factors and especially body mass index, a known determinant of endogenous hormone levels, attenuated most associations. In conclusion, several endogenous sex hormones may influence basal levels of inflammatory markers. Obesity appears to play a modulating role.


Androgens C-reactive protein Estrone Fibrinogen White blood cells 



Atherosclerosis Risk in Communities Study


body mass index


C-reactive protein


dehydroepiandrosterone sulfate


high density lipoprotein


standard deviation


sex hormone binding globulin


white blood cell


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Danesh, J, Whincup, P, Walker, M,  et al. 2000Low grade inflammation and coronary heart disease: prospective study and updated meta-analysisBMJ321199204PubMedGoogle Scholar
  2. 2.
    Ridker, PM 2001High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular diseaseCirculation10318131818PubMedGoogle Scholar
  3. 3.
    Cushman, M 2002Effects of hormone replacement therapy and estrogen receptor modulators on markers of inflammation and coagulationAm J Cardiol907F10FPubMedGoogle Scholar
  4. 4.
    Valk-de Roo, GW, Stehouwer, CD, Meijer, P,  et al. 1999Both raloxifene and estrogen reduce major cardiovascular risk factors in healthy postmenopausal women: a 2-year, placebo-controlled studyArterioscler Thromb Vasc Biol1929933000PubMedGoogle Scholar
  5. 5.
    Cushman, M, Legault, C, Barrett-Connor, E,  et al. 1999Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) studyCirculation100717722PubMedGoogle Scholar
  6. 6.
    Ridker, PM, Hennekens, CH, Rifai, N, Buring, JE, Manson, JE 1999Hormone replacement therapy and increased plasma concentration of C-reactive proteinCirculation100713716PubMedGoogle Scholar
  7. 7.
    Baal, WM, Kenemans, P, Mooren, MJ, Kessel, H, Emeis, JJ, Stehouwer, CD 1999Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal womenThromb Haemost81925928PubMedGoogle Scholar
  8. 8.
    Herrington, DM, Brosnihan, KB, Pusser, BE,  et al. 2001Differential effects of E and droloxifene on C-reactive protein and other markers of inflammation in healthy postmenopausal womenJ Clin Endocrinol Metab8642164222CrossRefPubMedGoogle Scholar
  9. 9.
    Luyer, MD, Khosla, S, Owen, WG, Miller, VM 2001Prospective randomized study of effects of unopposed estrogen replacement therapy on markers of coagulation and inflammation in postmenopausal womenJ Clin Endocrinol Metab8636293634CrossRefPubMedGoogle Scholar
  10. 10.
    Vehkavaara, S, Silveira, A, Hakala-Ala-Pietila, T,  et al. 2001Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal womenThromb Haemost85619625PubMedGoogle Scholar
  11. 11.
    Walsh, BW, Paul, S, Wild, RA,  et al. 2000The effects of hormone replacement therapy and raloxifene on C-reactive protein and homocysteine in healthy postmenopausal women: a randomized, controlled trialJ Clin Endocrinol Metab85214218CrossRefPubMedGoogle Scholar
  12. 12.
    Decensi, A, Omodei, U, Robertson, C,  et al. 2002Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy womenCirculation10612241228CrossRefPubMedGoogle Scholar
  13. 13.
    Skouby, SO, Gram, J, Andersen, LF, Sidelmann, J, Petersen, KR, Jespersen, J 2002Hormone replacement therapy: estrogen and progestin effects on plasma C-reactive protein concentrationsAm J Obstet Gynecol186969977CrossRefPubMedGoogle Scholar
  14. 14.
    Post, MS, Mooren, MJ, Stehouwer, CD,  et al. 2002Effects of transdermal and oral oestrogen replacement therapy on C-reactive protein levels in postmenopausal women: a randomised, placebo-controlled trialThromb Haemost88605610PubMedGoogle Scholar
  15. 15.
    Zegura, B, Keber, I, Sebestjen, M, Koenig, W 2003Double blind, randomized study of estradiol replacement therapy on markers of inflammation, coagulation and fibrinolysisAtherosclerosis168123129CrossRefPubMedGoogle Scholar
  16. 16.
    Vongpatanasin, W, Tuncel, M, Wang, Z, Arbique, D, Mehrad, B, Jialal, I 2003Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal womenJ Am Coll Cardiol4113581363CrossRefPubMedGoogle Scholar
  17. 17.
    Kluft, C, Leuven, JA, Helmerhorst, FM, Krans, HM 2002Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatmentVascul Pharmacol39149154PubMedGoogle Scholar
  18. 18.
    Lamon-Fava, S, Posfai, B, Schaefer, EJ 2003Effect of hormonal replacement therapy on C-reactive protein and cell-adhesion molecules in postmenopausal womenAm J Cardiol91252254CrossRefPubMedGoogle Scholar
  19. 19.
    Lacut K, Oger E, Le Gal G, et al. and the SARAH investigators. Differential effects of oral and transdermal postmenopausal estrogen replacement therapies on C-reactive protein. Thromb Haemost 2003; 90: 124–131Google Scholar
  20. 20.
    Modena, MG, Bursi, F, Fantini, G,  et al. 2002Effects of hormone replacement therapy on C-reactive protein levels in healthy postmenopausal women: comparison between oral and transdermal administration of estrogenAm J Med113331334CrossRefPubMedGoogle Scholar
  21. 21.
    Cushman, M, Costantino, JP, Tracy, RP,  et al. 2001Tamoxifen and cardiac risk factors in healthy women – Suggestion of an anti-inflammatory effectArterioscl Thromb Vasc Biol21255261PubMedGoogle Scholar
  22. 22.
    Zanger, D, Yang, BK, Ardans, J,  et al. 2000Divergent effects of hormone therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical managementJ Am Coll Cardiol3617971802CrossRefPubMedGoogle Scholar
  23. 23.
    Störk, S, Schacky, C, Angerer, P 2002The effect of 17β-estradiol on endothelial and inflammatory markers in postmenopausal women: a randomized, controlled trialAtherosclerosis165301307PubMedGoogle Scholar
  24. 24.
    Silvestri, A, Gebara, O, Vitale, C,  et al. 2003Increased levels of C-reactive protein after oral hormone replacement therapy may not be related to an increased inflammatory responseCirculation10731653169CrossRefPubMedGoogle Scholar
  25. 25.
    Lahita, RG 2000Sex hormones and systemic lupus erythematosusRheum Dis Clin North Am26951968CrossRefPubMedGoogle Scholar
  26. 26.
    Brooks-Asplund, EM, Tupper, CE, Daun, JM, Kenney, WL, Cannon, JG 2002Hormonal modulation of interleukin-6, tumor necrosis factor and associated receptor secretion in postmenopausal womenCytokine19193200CrossRefPubMedGoogle Scholar
  27. 27.
    Folsom, AR, Aleksic, N, Catellier, D, Juneja, H, Wu, KK 2002C-reactive protein and incident coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) StudyAm Heart J144233238CrossRefPubMedGoogle Scholar
  28. 28.
    Marette, A 2002Mediators of cytokine-induced insulin resistance in obesity and other inflammatory settingsCurr Opin Clin Nutr Metab Care5377383CrossRefPubMedGoogle Scholar
  29. 29.
    Zumoff, B 1988Hormonal abnormalities in obesityActa Med Scand Suppl723153160PubMedGoogle Scholar
  30. 30.
    Jilma, B, Dirnberger, E, Löscher, I,  et al. 1997Menstrual cycle-associated changes in blood levels of interleukin-6, alpha1 acid glycoprotein, and C-reactive proteinJ Lab Clin Med1306975CrossRefPubMedGoogle Scholar
  31. 31.
    Ricoux, R, Pontet, M, Tresca, JP, Engler, R 1994[Plasma concentration of C-reactive protein in patients with high estrogen levels]Ann Biol Clin52125128 (French)Google Scholar
  32. 32.
    Golden, SH, Maguire, A, Ding, J,  et al. 2002Endogenous postmenopausal hormones and carotid atherosclerosis: a case–control study of the Atherosclerosis Risk in Communities cohortAm J Epidemiol155437445CrossRefPubMedGoogle Scholar
  33. 33.
    Miller, VT, Larosa, J, Barnabei, V,  et al. 1995Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) trialJAMA273199208CrossRefGoogle Scholar
  34. 34.
    Angerer, P, Stork, S, Kothny, W, Schmitt, P, Schacky, C 2001Effect of oral postmenopausal hormone replacement on progression of atherosclerosis: a randomized, controlled trialArterioscler Thromb Vasc Biol21262268PubMedGoogle Scholar
  35. 35.
    Andersen, LF, Gram, J, Skouby, SO, Jespersen, J 1999Effects of hormone replacement therapy on hemostatic cardiovascular risk factorsAm J Obstet Gynecol180283289PubMedGoogle Scholar
  36. 36.
    Baal, WM, Kenemans, P, Emeis, JJ,  et al. 1999Long-term effects of combined hormone replacement therapy on markers of endothelial function and inflammatory activity in healthy postmenopausal womenFertil Steril71663670PubMedGoogle Scholar
  37. 37.
    The ARIC Investigators1989The Atherosclerosis Risk in Communities (ARIC) Study: Design and objectivesAm J Epidemiol129687702Google Scholar
  38. 38.
    Riley, WA, Barnes, R, Bond, MG, Evans, G, Chambless, LE, Heiss, G 1991High resolution B-mode ultrasound reading methods in the Atherosclerosis Risk in Communities Study (ARIC)J Neuroimag1168172Google Scholar
  39. 39.
    Clauss, A 1957Gerinnungsphysiologische Schnellmethode zur Bestimmung des FibrinogensActa Haematol17237246PubMedCrossRefGoogle Scholar
  40. 40.
    White, AD, Folsom, AR, Chambless, LE,  et al. 1996Community surveillance of coronary heart disease in the Atherosclerosis Risk in Communities (ARIC) Study: methods and initial two years’ experienceJ Clin Epidemiol49223233PubMedGoogle Scholar
  41. 41.
    Folsom, AR, Qamhieh, HT, Wing, RR,  et al. 1993Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adultsArterioscler Thromb13162169PubMedGoogle Scholar
  42. 42.
    Oh, JY, Barrett-Connor, E, Wedick, NM, Wingard, DL 2002Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo StudyDiabetes Care255560PubMedGoogle Scholar
  43. 43.
    Cauley, JA, Gutai, JP, Kuller, LH, Powell, JG 1991Reliability and interrelations among serum sex hormones in postmenopausal womenAm J Epidemiol1335057PubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Aaron R. Folsom
    • 1
  • Sherita Hill Golden
    • 2
  • Lori L. Boland
    • 1
  • Moyses Szklo
    • 3
  1. 1.Division of Epidemiology and Community Health, School of Public HealthUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of Epidemiology, Johns Hopkins Bloomberg School of Public HealthJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations