Kuiper, et al: Menopausal state and RA 1809 From the Department of Rheumatology and Department of Medical Statistics, University Medical Center Nijmegen, Nijmegen, the Netherlands; and Department of Rheumatology, Hospitais da Universidade de Coimbra, Coimbra, Portugal. S. Kuiper, MSc; A.M. van Gestel, MSc; H.L. Swinkels MSc; T.M. de Boo, MSc; P.L.C.M. van Riel, MD, PhD, Professor of Rheumatology, University Medical Center Nijmegen; J.A.P. da Silva, MD, PhD, Professor of Rheumatology, Hospitais da Universidade de Coimbra. Address reprint requests to Prof. Dr. P.L.C.M. van Riel, Department of Rheumatology, University Medical Center St. Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: P.vanRiel@reuma.azn.nl Submitted September 13, 2000; revision accepted February 12, 2001. Rheumatoid arthritis (RA) is a chronic systemic disorder of unknown etiology characterized by symmetric synovitis with a prevalence at present of less than 1% of the Caucasian adult population 1 . Within this population, women are more frequently afflicted with RA than men, with a ratio of 2–3:1 2,3 . In most patients the disease course is fluctuating, which often results in a progressive destruction of the joints. Many factors have been described to influence the disease course and outcome 4,5 . However, due to conflicting results, agreement only exists about a few of these, such as IgM rheumatoid factor (IgM-RF), disease activity, and female sex 6-9 . It is becoming more accepted that there are gender differences in the susceptibility and the response to several illnesses 10 . There is agreement that there are differ- ences between women and men in terms of RA progression. There is, however, no agreement in whether women or men have a more severe disease course. Several authors have shown that men tend to have a better prognosis in terms of radiographic joint damage 6 and functional capacity as measured by the Health Assessment Questionnaire (HAQ) 7–9 . On the other hand, Weyand, et al 11 have shown that men have a more aggressive disease course in terms of nodules and rheumatoid lung disease. In animal models sex differences were seen in experiments on cartilage, where female rats and mice experienced degraded cartilage faster than males 12,13 . Compared to their male counterparts, female mice were more susceptible to proteoglycan induced polyarthritis 14 and female rats to chronic polyarthritis induced with streptococcal cell wall preparation. An explanation for the different opinions regarding the role of sex in disease progression might be the changes in the hormonal state of women in certain periods of life. The use of oral contraceptive (OC) hormones, pregnancy, or the menopause and whether hormone replacement therapy (HRT) has been used in this period might have an influence on disease course. Studies concerning the effect of female Influence of Sex, Age, and Menopausal State on the Course of Early Rheumatoid Arthritis SANDRAKUIPER, ANKE M. van GESTEL, HILDE L. SWINKELS, THEO M. de BOO, JOSÉ A.P. da SILVA, PIET L.C.M. van RIEL ABSTRACT. Objective. To investigate the influences of the menopausal state, sex, and age on the course and outcome of rheumatoid arthritis (RA). Methods. A cohort of patients with early RA (209 female, 123 male) was studied. Sex, age, and menopausal state at baseline, and disease activity, radiographic joint destruction, and physical disability during 6 years of followup were assessed. Results. The Disease Activity Score (DAS) was significantly higher in female compared to male patients at any time point except at the time of inclusion. This was mainly due to postmenopausal patients. Radiographic joint destruction (RJD) was significantly worse in female patients compared to males at the time of inclusion. Postmenopausal patients had significantly higher RJD than premenopausal patients at the time of inclusion and 3 years thereafter. Older male patients showed worse RJD than younger male patients at all time points measured. Physical disability was signifi- cantly worse in female compared to male patients, as well as in postmenopausal compared to premenopausal patients, and older male compared to younger male patients. Stepwise regression analysis revealed that at 3 years higher age and female sex were the best predictors for a worse DAS. Higher age and the interaction term between menopausal state and age best predicted higher RJD. Higher age and the interaction term between menopausal state and age best predicted Health Assessment Questionnaire (HAQ) score. Conclusion. Higher age at presentation of RA leads to a more severe disease course in terms of DAS, RJD, and HAQ. Although female sex has a deteriorating effect on the DAS, the menopausal state is responsible for the major part of the differences in outcome between men and women. Postmenopausal state in early RA influences future disability and damage, especially in older patients. (J Rheumatol 2001;28:1809–16) Key Indexing Terms: RHEUMATOID ARTHRITIS DISEASE ACTIVITY MENOPAUSE AGE SEX Personal non-commercial use only. The Journal of Rheumatology Copyright © 2001. All rights reserved. www.jrheum.org Downloaded on January 13, 2022 from