Reduction of the risk of rheumatoid arthritis among women who take oral contraceptives
Corresponding Author
Johanna M. W. Hazes MD
Department of Rheumatology
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Department of Rheumatology, Building 1, C2-Q, University Hospital Leiden, PO Box 9600, Leiden 2300 RC, The NetherlandsSearch for more papers by this authorBen A. C. Dijkmans MD
Department of Rheumatology
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Search for more papers by this authorJan P. Vandenbroucke MD, PhD
Department of Clinical Epidemiology
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Search for more papers by this authorRené R. P. De Vries MD
Department of Immunohematology/Blood Bank
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Search for more papers by this authorArnold Cats MD
Department of Rheumatology
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Search for more papers by this authorCorresponding Author
Johanna M. W. Hazes MD
Department of Rheumatology
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Department of Rheumatology, Building 1, C2-Q, University Hospital Leiden, PO Box 9600, Leiden 2300 RC, The NetherlandsSearch for more papers by this authorBen A. C. Dijkmans MD
Department of Rheumatology
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Search for more papers by this authorJan P. Vandenbroucke MD, PhD
Department of Clinical Epidemiology
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Search for more papers by this authorRené R. P. De Vries MD
Department of Immunohematology/Blood Bank
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Search for more papers by this authorArnold Cats MD
Department of Rheumatology
Departments of Rheumatology, Clinical Epidemiology, and Immunohematology/Blood Bank, University Hospital, Leiden, The Netherlands.
Search for more papers by this authorAbstract
Discrepant results among investigations of the association between oral contraceptive use and rheumatoid arthritis (RA) have been ascribed to shortcomings in the study methods. In the present study, we obtained detailed information on oral contraceptive use in 135 young women with confirmed definite or classic RA of recent onset and in 378 controls with soft tissue rheumatism or osteoarthritis. All patients had at least 2 years of followup to confirm the consistency of the diagnosis. Oral contraceptive use at any time before disease onset was reported by 70% of the RA patients and 85% of the controls; the latter figure corresponded to general population data for The Netherlands. This yielded a relative risk for RA of 0.39 among those who had ever used oral contraceptives and 0.58 for those using oral contraceptives at the time of symptom onset. The preventive effect of oral contraceptive use on the risk of RA was found to be independent of the dose, duration of use, or presence of HLA-DR4. The strongest protection was seen in women with a family history of RA and in women ages 31–40 at symptom onset. The conflicting results in the literature are discussed, and a possible biologic mechanism for this phenomenon is suggested.
References
- 1 Wingrave SJ, Kay CR: Reduction in incidence of rheumatoid arthritis associated with oral contraceptives. Lancet I: 569–571, 1978
- 2 Vandenbroucke JP, Valkenburg HA, Boersma JW, Cats A, Festen JJM, Huber-Bruning O, Rasker JJ: Oral contraceptives and rheumatoid arthritis: further evidence for a preventive effect. Lancet II: 839–842, 1982
- 3 Vandenbroucke JP, Witteman JCM, Valkenburg HA, Boersma JW, Cats A, Festen JJM, Hartman AP, Huber-Bruning O, Rasker JJ, Weber J: Noncontraceptive hormones and rheumatoid arthritis in perimenopausal and postmenopausal women. JAMA 255: 1299–1303, 1986
- 4
Linos A,
Worthington JW,
O'Fallon WM,
Kurland LT:
Case-control study of rheumatoid arthritis and prior use of oral contraceptives.
Lancet
I:
1299–1300,
1983
10.1016/S0140-6736(83)92413-3 Google Scholar
- 5 Del Junco DJ, Annegers JF, Luthra HS, Coulam CB, Kurland LT: Do oral contraceptives prevent rheumatoid arthritis? JAMA 254: 1938–1941, 1985
- 6 Allebeck P, Ahlbom A, Ljungstrom K, Allander E: Do oral contraceptives reduce the incidence of rheumatoid arthritis? Scand J Rheumatol 13: 140–146, 1984
- 7 Vessey MP, Villard-Mackintosh L, Yeates D: Oral contraceptives, cigarette smoking and other factors in relation to arthritis. Contraception 35: 457–464, 1987
- 8 Hernandez-Avila M, Liang M, Willett WC, Stampfer MJ, Colditz G, Rosner B, Hennekens CH, Speizer FE: Oral contraceptives and postmenopausal hormone use and the risk of rheumatoid arthritis (abstract). Arthritis Rheum 31 (suppl 4): S36, 1988
- 9. Spector T, Silman A, Roman E: Protective effect of prior oral contraceptive use for rheumatoid arthritis (abstract). Arthritis Rheum 31 (suppl 4): S58, 1988
- 10
Berry H:
Rheumatoid arthritis and oral contraception.
Lancet
I:
829,
1978
10.1016/S0140-6736(78)93037-4 Google Scholar
- 11
Shapiro S:
Rheumatoid arthritis, the pill, and self-selection (letter).
Lancet
II:
1282,
1982
10.1016/S0140-6736(82)90140-4 Google Scholar
- 12 Hazes JMW, Dijkmans BAC: Do oral contraceptives prevent rheumatoid arthritis? JAMA 256: 215–216, 1986
- 13 Esdaile JM, Horwitz RI: Observational studies of cause-effect relationships: an analysis of methodologic problems as illustrated by the conflicting data for the role of oral contraceptives in the etiology of rheumatoid arthritis. J Chronic Dis 39: 841–852, 1986
- 14 Spector TD, Silman AJ: Observational studies of cause-effect relationships: an analysis of methodological problems as illustrated by the conflicting data for the role of oral contraceptives in the etiology of rheumatoid arthritis (letter). J Chronic Dis 40: 1063–1064, 1987
- 15 Esdaile JM, Horwitz RI: Response (letter). J Chronic Dis 40: 1065–1067, 1987
- 16 Vandenbroucke JP: A check-list for observational research? J Chronic Dis 40: 1067–1068, 1987
- 17 Khoury MJ, Stewart W, Beaty TH: The effect of genetic susceptibility on causal inference in epidemiologic studies. Am J Epidemiol 126: 561–567, 1987
- 18 Stastny P: Association of the B-cell alloantigen DR4 with rheumatoid arthritis. N Engl J Med 298: 869–871, 1978
- 19 Panayi GS, Wooley P, Batchelor JR: Genetic basis of rheumatoid disease: HLA antigens, disease manifestations, and toxic reactions to drugs. Br Med J 2: 1326–1328, 1978
- 20 Karr RW, Rodey GE, Lee T, Schwartz BD: Association of HLA-DR4 with rheumatoid arthritis in black and white patients. Arthritis Rheum 23: 1241–1245, 1980
- 21 De Vries RRP, Nijenhuis LE, Khan MA, Mehra NK: Paradoxical inheritance of HLA-linked susceptibility of rheumatoid arthritis. Tissue Antigens 26: 286–292, 1985
- 22 De Jongh BM, van Romunde LK, Valkenburg HA, de Lang GG, van Rood JJ: Epidemiological study of HLA and GM in rheumatoid arthritis and related symptoms in an open Dutch population. Ann Rheum Dis 43: 613–619, 1984
- 23 Westedt ML, Breedveld FC, Schreuder GMT, d'Amaro J, Cats A, de Vries RRP: Immunogenetic heterogeneity of rheumatoid arthritis. Ann Rheum Dis 45: 534–538, 1986
- 24 De Jongh BM, Westedt ML, de Vries RRP, Valkenburg HA, Cats A: Genetic heterogeneity of rheumatoid arthritis. Dis Markers 4: 29–33, 1986
- 25 Ropes MW, Bennett GA, Cobb S, Jacox R, Jessar RA: 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9: 175–176, 1958
- 26 Van Sonsbeek JLA: Health Interview Surveys: pillconsumption in 1981–1986. Maandbericht gezondheid (Central Bureau of Statistics, The Netherlands) 7: 5–7, 1987
- 27 Van Rood JJ, van Leeuwen A, Ploem JS: Simultaneous detection of two cell populations by two-colour fluorescence and application to the recognition of B-cell determinants. Nature 262: 795–797, 1976
- 28 Woolf B: On estimating the relation between blood group and disease. Ann Hum Genet 19: 251–253, 1955
- 29 Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. JNCI 22: 719–748, 1959
- 30 Miettinen OS: Estimability and estimation in casereferent studies. Am J Epidemiol 103: 226–235, 1976
- 31 Schlesselman JJ: Case-Control Studies. Design, Conduct, Analysis. New York, Oxford University Press, 1982
- 32 Linos A, Worthington JW, O'Fallon WM, Kurland LT: The epidemiology of rheumatoid arthritis in Rochester, Minnesota: a study of incidence, prevalence and mortality. Am J Epidemiol 111: 87–98, 1980
- 33 Vandenbroucke JP, Hazevoet HM, Cats A: Survival and cause of death in rheumatoid arthritis: a 25-year prospective follow-up. J Rheumatol 11: 158–161, 1984
- 34 Mitchell DM, Spitz PW, Young DY, Bloch DA, McShane DJ, Fries JF: Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis Rheum 29: 706–714, 1986
- 35 Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA Jr, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31: 315–324, 1988
- 36 Grossman CJ: Regulation of the immune system by sex steroids. Endocr Rev 5: 435–455, 1984
- 37 Grossman CJ: Interactions between gonadal steroids and the immune system. Science 227: 257–261, 1985
- 38 Lahita RG: Sex steroids and the rheumatic diseases. Arthritis Rheum 28: 121–126, 1985
- 39 Buyon JP, Korchak HM, Rutherford LE, Ganguly M, Weissmann G: Female hormones reduce neutrophil responsiveness in vitro. Arthritis Rheum 27: 623–630, 1984
- 40 Luster MI, Hayes HT, Korach K, Tucker AN, Dean JH, Greenlee WF, Boorman GA: Estrogen immunosuppression is regulated through estrogenic responses in the thymus. J Immunol 133: 110–116, 1984
- 41 Weusten JJAM, Blankenstein MA, Gmelig-Meyling FHJ, Schuurman HJ, Kater L, Thijssen JHH: Presence of oestrogen receptors in human blood mononuclear cells and thymocytes. Acta Endocrinol 112: 409–414, 1986
- 42 Holoshitz J, Naparstek Y, Ben-Nun A, Cohen IR: Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. Science 219: 56–58, 1983
- 43 Holmdahl R, Klareskog L, Rubin K, Larsson E, Wigzell H: T lymphocytes in collagen II-induced arthritis in mice: characterization of arthntogenic collagen II-specific T-cell lines and clones. Scand J Immunol 22: 295–306, 1985
- 44 Kappers A, Jones HEH, Roitt IM: Effects of steroid sex hormones on immunological phenomena. Nature 198: 902–903, 1963
- 45 Toivanen P, Sükala H, Laiho P, Paavilainen T: Suppression of adjuvant arthritis by estrone in adrenalectomized and ovariectomized rats. Experientia 23: 560–561, 1968
- 46 Holmdahl R, Jansson L, Andersson M: Female sex hormones suppress development of collagen-induced arthritis in mice. Arthritis Rheum 29: 1501–1509, 1986
- 47 Silman AJ: Is pregnancy a risk factor in the causation of rheumatoid arthritis? Ann Rheum Dis 45: 1031–1034, 1986