Abstract
IntroductionRheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference. We conducted a case–control study nested within two prospective studies to determine the associations between plasma steroid hormones measured prior to RA onset and polymorphisms in the androgen receptor (AR), estrogen receptor 2 (ESR2), aromatase (CYP19) and progesterone receptor (PGR) genes and RA risk.MethodsWe genotyped AR, ESR2, CYP19, PGR SNPs and the AR CAG repeat in RA case–control studies nested within the Nurses' Health Study (NHS), NHS II (449 RA cases, 449 controls) and the Women's Health Study (72 cases, and 202 controls). All controls were matched on cohort, age, Caucasian race, menopausal status, and postmenopausal hormone use. We measured plasma dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin in 132 pre-RA samples and 396 matched controls in the NHS cohorts. We used conditional logistic regression models adjusted for potential confounders to assess RA risk.ResultsMean age of RA diagnosis was 55 years in both cohorts; 58% of cases were rheumatoid factor positive at diagnosis. There was no significant association between plasma DHEAS, total testosterone, or calculated free testosterone and risk of future RA. There was no association between individual variants or haplotypes in any of the genes and RA or seropositive RA, nor any association for the AR CAG repeat.ConclusionsSteroid hormone levels measured at a single time point prior to RA onset were not associated with RA risk in this study. Our findings do not suggest that androgens or the AR, ESR2, PGR, and CYP19 genes are important to RA risk in women.
Highlights
Rheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference
Steroid hormone levels measured at a single time point prior to rheumatoid arthritis (RA) onset were not associated with RA risk in this study
Our findings do not suggest that androgens or the androgen receptor (AR), estrogen receptor 2 (ESR2), progesterone receptor (PGR), and CYP19 genes are important to RA risk in women
Summary
Rheumatoid arthritis (RA) is more common in females than males and sex steroid hormones may in part explain this difference. Women are two to four times more likely than men to develop rheumatoid arthritis (RA) [1,2], and sex hormones including androgens, estrogen, and progesterone may be related to this disparity [3,4]. Cross-sectional studies of serum androgen levels demonstrate low serum testosterone levels and dehydroepiandrosterone sulfate (DHEAS) in RA patients compared with healthy individuals [6,7,8,9,10]. One small prospective study demonstrated low DHEAS among premenopausal pre-RA women compared with control individuals [17], while another study demonstrated no differences in total testosterone or DHEAS levels in male and female pre-RA cases compared with sex-matched control individuals [18]
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