Association between testosterone levels and risk of future rheumatoid arthritis in men: a population-based case–control study

Pikwer, Mitra; Giwercman, Aleksander; Bergström, Ulf; Nilsson, Jan‐Åke; Jacobsson, Lennart; Turesson, Carl

doi:10.1136/annrheumdis-2012-202781

Cited by 58 publications

(41 citation statements)

References 36 publications

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“…In their study of 32 males in Finland, Heikkila et al [11] reported no association between baseline serum testosterone levels and the subsequent development of rheumatoid arthritis. By contrast, in their nested case–control study of 278 patients, Pikwer et al [12] reported that low serum testosterone was predictive of RF-negative rheumatoid arthritis. A small number of clinical trials have also yielded conflicting results.…”

Section: Discussionmentioning

confidence: 95%

Hypogonadism and the risk of rheumatic autoimmune disease

et al. 2016

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Testosterone deficiency has been linked with autoimmune disease and an increase in inflammatory markers, such as C-reactive protein (CRP), tumor necrosis factor, and interleukin-6 (IL-6). However, no large-scale longitudinal studies have examined this association. We examined whether untreated hypogonadism was associated with an increased risk of rheumatic autoimmune disease in a large nationally representative cohort. Using one of the nation’s largest commercial insurance databases, we conducted a retrospective cohort study in which we identified 123,460 men diagnosed with hypogonadism between January 1, 2002 and December 31, 2014 and with no prior history of rheumatic autoimmune disease. We matched this cohort to 370,380 men without hypogonadism, at a 1 to 3 ratio, on age and index/diagnosis date. All patients were followed until December 31, 2014 or until they lost insurance coverage or were diagnosed with a rheumatic autoimmune disease. Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHRs). Untreated hypogonadism was associated with an increased risk of developing any rheumatic autoimmune disease (HR = 1.33, 95 % CI = 1.28, 1.38), rheumatoid arthritis (HR = 1.31, 95 % CI = 1.22, 1.44), and lupus (HR = 1.58, 95 % CI = 1.28, 1.94). These findings persisted using latency periods of 1 and 2 years. Hypogonadism was not associated with the control outcome, epilepsy (HR = 1.04, 95 % CI = 0.96, 1.15). Patients diagnosed with hypogonadism who were not treated with testosterone had an increased risk of developing any rheumatic autoimmune disease, rheumatoid arthritis, and lupus. Future research should further examine this association, with particular attention to underlying mechanisms.

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Section: Discussionmentioning

confidence: 95%

Hypogonadism and the risk of rheumatic autoimmune disease

et al. 2016

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“…But the exact role of sex hormones in the pathogenesis and progression of lung cancer remains unclear, and there are actually some dramatic discrepancies in publishing reports. For example, certain studies suggested that androgens such as testosterone were decreased whereas estrogens such as estradiol were increased in patients with lung cancer (12,18). But in other studies, there were no such associations observed.…”

Section: Discussionmentioning

confidence: 99%

Decreased levels of circulating sex hormones as a biomarker of lung cancer in male patients with solitary pulmonary nodules

Gu¹,

Wen²,

Xu³

et al. 2014

Afr H. Sci.

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“…However, low levels of testosterone have been associated with an increased risk of autoimmune rheumatoid arthritis (RA) in men (79) and, in addition, testosterone can suppress superoxide production and microbicidal activity in neutrophils, and thus influence the inflammatory response (80). Furthermore, an increase in testosterone levels suppresses the expression of the pro-inflammatory cytokines, such as TNFα, IL-1β, and IL-6 and potentiate the expression of the anti-inflammatory cytokine IL-10 (81, 82), which has been shown to inhibit neutrophil phagocytic and bactericidal activity, and down-regulate some cell-surface proteins, such as CD11b, pointing toward a less mature phenotype (83, 84).…”

Section: Discussionmentioning

confidence: 99%

Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy

Blažková

Gupta

Liu

et al. 2017

The Journal of Immunology

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Despite clear differences in immune system responses and in the prevalence of autoimmune diseases between males and females, there is little understanding of the processes involved. Here, we identified a gene signature of immature-like neutrophils (Immature-Like Neutrophil Signature, ILNS), characterized by the overexpression of genes encoding for several granule-containing proteins, which was found in higher levels (up to 3-fold) in young (20 – 30 years old) but not older (60 – >89 years old) males compared with females. Functional and phenotypic characterization of peripheral blood neutrophils revealed more mature and responsive neutrophils in young females, which also exhibited an elevated capacity in neutrophil extracellular trap (NET) formation at baseline and upon microbial or sterile autoimmune stimuli. Expression levels of the ILNS increased linearly with pregnancy, an immune state of increased susceptibility to and severity of certain infections. Using mass cytometry, we also find increased frequencies of immature forms of neutrophils in the blood of women in late pregnancy. Thus, our findings show novel sex-differences in innate immunity and identify a common neutrophil signature in males and in pregnant women.

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Association between testosterone levels and risk of future rheumatoid arthritis in men: a population-based case–control study

Abstract: Lower levels of testosterone were predictive of RF-negative RA, suggesting that hormonal changes precede the onset of RA and affect the disease phenotype.

Cited by 58 publications

References 36 publications

Hypogonadism and the risk of rheumatic autoimmune disease

Hypogonadism and the risk of rheumatic autoimmune disease

Decreased levels of circulating sex hormones as a biomarker of lung cancer in male patients with solitary pulmonary nodules

Multicenter Systems Analysis of Human Blood Reveals Immature Neutrophils in Males and During Pregnancy

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