Controlled Cohort Study of Serum Gonadal and Adrenocortical Steroid Levels in Males Prior to Onset of Rheumatoid Arthritis (pre-RA): A Comparison to pre-RA Females and Sex Differences among the Study Groups
Serum testosterone levels are generally reported to be lower in male rheumatoid arthritis (RA) patients, but it is not determined if a deficiency may occur before clinical onset of disease (pre-RA). Lower testosterone levels were recently reported in males many years before RA onset but were predictive only of rheumatoid factor (RF)—negative disease. A preceding prospective study did not reveal androgenic-anabolic hormone association with risk of RA in men or women. This cohort study of males analyzed baseline serum levels of gonadal and adrenocortical steroids, luteinizing hormone, and prolactin in 18 pre-RA versus 72 matched non-RA control (CN) subjects. Findings in males were compared to those in female pre-RA and CN subjects in the same cohort, and sex differences were analyzed. Steroidal and hormonal levels, including total testosterone, were similar between male study groups. In females, mean (±SE) serum androstenedione (nmol/L) was slightly ( ) lower in 36 pre-RA (6.7 ± 0.36) than 144 CN (7.6 ± 0.22). With the exception of 3 partial correlations of hormonal variables observed to differ between pre-RA versus CN subjects, the patterns were similar overall. However, partial correlations of hormonal variables differed frequently by sex, both within and between study groups. 1. Introduction The onset of rheumatoid arthritis (RA) occurs about 5-fold more frequently in women of child-bearing ages than among male counterparts [1]. Early age at menopause (≤45？yrs) was recently found to be associated with the subsequent risk of developing RA [2]. Such findings suggest that sex hormones may influence predisposition to this disease in women. In male RA patients with active disease, testosterone levels are reported to be lower than those in healthy control (CN) subjects [3, 4]. However, it is not known if such hormonal alteration results from inflammatory manifestations of active clinical disease or if it may be a preexisting risk factor before clinical onset (pre-RA). Recently, testosterone levels were reported to be lower in males many years before RA onset, as identified in a large Swedish cohort [5]. However, a significant association of lower testosterone levels was predictive only for the minority subset of patients having negative rheumatoid factor (RF-negative) disease [5]. A preceding retrospective case-control nested study within a large Finnish cohort did not find baseline serum total testosterone or dehydroepiandrosterone sulfate (DHEAS) levels to be predictive of the subsequent onset of RA, either in 32-male or in 84-female cases [6]. Our
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