Hypogonadism and the risk of rheumatic autoimmune disease.
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.
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA. jbaillar@utmb.edu.|Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA. jbaillar@utmb.edu.|Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, TX, USA. jbaillar@utmb.edu.
Jacques
J
Baillargeon
Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA.|Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, TX, USA.
Soham
S
Al Snih
Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA.|Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, TX, USA.|Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Mukaila A
MA
Raji
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Randall J
RJ
Urban
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Gulshan
G
Sharma
Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA.|Department of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, TX, USA.|Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Melinda
M
Sheffield-Moore
Division of Epidemiology, University of Texas Health Science Center at Houston, School of Public Health, Houston, TX, USA.
David S
DS
Lopez
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA.
Gwen
G
Baillargeon
Department of Preventive Medicine and Community Health, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA.|Sealy Center on Aging, University of Texas Medical Branch, Galveston, TX, USA.|Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Yong-Fang
YF
Kuo
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000150:complications* / Q000453:epidemiology; D002097:C-Reactive Protein / Q000737:chemistry; D006801:Humans; D007006:Hypogonadism / Q000150:complications* / Q000453:epidemiology; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000150:complications* / Q000453:epidemiology; D012307:Risk Factors; D013739:Testosterone / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013739:Testosterone; D002097:C-Reactive Protein
Androgen; Autoimmune disease; Rheumatic disease; Testosterone replacement therapy