Postmenopausal hormone therapy and the risk of rheumatoid arthritis: results from the Swedish EIRA population-based case-control study.

Cecilia Orellana,Saedis Saevarsdottir,Elizabeth W Karlson,Camilla Bengtsson,Lars Alfredsson,Lars Klareskog

doi:10.1007/s10654-015-0004-y

Abstract

To study the association between postmenopausal hormone therapy (PMH) use and the risk of rheumatoid arthritis (RA) stratifying the cases by the presence/absence of antibodies against citrullinated peptides (ACPA). A subset of the Epidemiological Investigation of RA (EIRA), a population-based case-control study, comprising postmenopausal women aged 50–70 living in Sweden, between 2006 and 2011 was analysed (523 cases and 1057 controls). All participants answered an extensive questionnaire, including questions regarding PMH use and potential confounders (education, smoking, BMI, oral contraceptives, reproductive factors). We calculated odds ratios (OR) of developing ACPA-positive/-negative RA, with 95 % confidence intervals (CI) and adjusted for age, residential area and smoking. Current users of PMH had a decreased risk of ACPA-positive RA compared with never users (OR 0.6, 95 % CI 0.3–0.9). The decreased risk was observed mainly in the age-group 50–59 years (OR 0.3, 95 % CI 0.1–0.8) but not in the age-group 60–70 years (OR 0.8, 95 % CI 0.4–1.4). Among current users of a combined therapy (estrogen plus progestogens) an OR of 0.3 (95 % CI 0.1–0.7) of ACPA-positive RA was observed, while no significant association was found among women who used estrogen only (OR 0.8, 95 % CI 0.5–1.6). No association between PMH use and ACPA-negative RA was found. PMH use might reduce the risk of ACPA-positive RA in post-menopausal women over 50 years of age, but not of ACPA-negative RA. The negative influence of this treatment on the risk of other chronic conditions cannot be overlooked.

Highlights

Rheumatoid arthritis (RA) is among the most common autoimmune diseases, a criterium based syndrome characterized by chronic inflammation in joints, with a multifactorial etiology [1, 2]
Current users of postmenopausal hormone therapy (PMH) had a decreased risk of developing ACPA-positive rheumatoid arthritis (RA) compared with never users in the adjusted model, but no association was found for past users
Our data demonstrate a decreased risk of developing ACPA-positive RA among postmenopausal women who were currently using PMH at onset of their disease. This decreased risk was mainly present among women aged 50–59 years and only among users of a combined therapy of estrogen and progestogens, the number of individuals were low in several subgroups

Summary

Introduction

Rheumatoid arthritis (RA) is among the most common autoimmune diseases, a criterium based syndrome characterized by chronic inflammation in joints, with a multifactorial etiology [1, 2]. A higher incidence of RA is seen among women compared to men across all ages, [4,5,6] and the highest incidence among women has been reported between 55 and 64 years of age, during the peri- or postmenopausal stage, [4, 6] one study has reported a later peak [7]. Hormonal factors, such as estrogen, have been hypothesized to be of importance for disease development. To the best of our knowledge, no study has investigated the association between PMH use and the risk of ACPA-positive as compared to ACPAnegative RA in a setting where exposure to PMH was ascertained in a healthy population

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