Association of serum testosterone and dehydroepiandrosterone sulfate with rheumatoid arthritis: a case control studyAssociation of serum testosterone and dehydroepiandrosterone sulfate with rheumatoid arthritis
A case control study
Keywords:
Rheumatoid arthritis, Dehydroepiandrosterone sulfate, Androgens, Humoral immunity, Cellular immunityAbstract
Background: It is supposed that hypoandrogenism may be involved in the pathogenesis of rheumatoid arthritis (RA). Testosterone and dehydroepiandrosterone sulfate (DHEAs) levels decrease in body fluids of patients with RA. Objective: The aim of this study was to determine the association of serum testosterone and DHEAs with RA. Methods: This case-control study was conducted on 59 patients with RA and 61 healthy gender- and age-matched controls at Qazvin University of Medical Sciences, Qazvin, Iran, in 2014. Serum free testosterone and DHEAs levels were measured and compared between two groups. Serum testosterone levels lower than 0.029 ng/ml in females and 2.49 ng/ml in males were considered as abnormal. DHEAs levels lower than 18.9 µg/dl in females and 88.9 µg/dl in males were considered as abnormal. Data were analyzed using independent sample T-test, Chi-square test, and logistic regression analysis by SPSS software, version 19. Results: The mean testosterone level in females of the control group was significantly higher than females in the case group. The mean DHEAs in the control group was significantly higher than the case group. Abnormal testosterone and DHEAs level in the case group was significantly higher than the control group. Logistic regression analysis showed independent association only between DHEAs levels and RA, after adjusting for age and gender (OR: 0.966, 95% CI: 0.953-0.979; p<0.001). Conclusion: With regard to the results, abnormal testosterone and DHEAs level in patients with RA was significantly higher than the control group. This shows the anti-inflammatory effects of gonadal and adrenal androgens in RAReferences
Kahlenberg JM, Fox DA. Advances in the medical treatment of rheumatoid arthritis. Hand Clin. 2011;27(1): 11-20. doi: 10.1016/j.hcl.2010.09.002. PMID:21176795, PMCID: PMC3135413.2)Bax M, Van Heemst J, Huizinga TW, Toes RE. Genetics of rheumatoid arthritis: what have we learned?Immunogenetics. 2011; 63(8): 459-66. doi: 10.1007/s00251-011-0528-6. PMID: 21556860, PMCID:PMC3132380.3)Simard JF, CostenbaderKH, Hernán MA, Liang MH, Mittleman MA, Karlson EW. Early life factors andadult-onset rheumatoid arthritis. J Rheumatol. 2010; 37(1): 32-7. doi: 10.3899/jrheum.090237. PMID:19833745, PMCID: PMC2800173.4)Heidari B. Rheumatoid Arthritis: Early diagnosis andtreatment outcomes. Caspian J Intern Med. 2011;2(1): 161-70. PMID: 24024009, PMCID: PMC3766928.5)Kahlenberg JM, Fox DA. Advances in the medical treatment of rheumatoid arthritis. Hand Clin. 2011;27(1): 11-20. doi: 10.1016/j.hcl.2010.09.002. PMID: 21176795, PMCID: PMC3135413.6)Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 rheumatoid arthritisclassification criteria: an American College of Rheumatology/European League Against Rheumatismcollaborative initiative. Ann RheumDis. 2010; 69(9): 1580-8. doi: 10.1136/ard.2010.138461. PMID:20699241.7)Kyburz D, Finckh A. The importance of early treatment for the prognosis of rheumatoid arthritis. SwissMed Wkly. 2013; 143: w13865. doi: 10.4414/smw.2013.13865. PMID: 24089023.8)Demoruelle MK, Deane K. Antibodies to citrullinated protein antigens (ACPAs): clinical andpathophysiologic significance. Curr Rheumatol Rep. 2011; 13(5): 421-30. doi: 10.1007/s11926-011-0193-7. PMID: 21713412, PMCID: PMC4095867.9)Puszczewicz M, Iwaszkiewicz C. Role of anti-citrullinated protein antibodies in diagnosis and prognosis ofrheumatoid arthritis. Arch Med Sci. 2011; 7(2): 189-94. doi: 10.5114/aoms.2011.22067. PMID: 22291756,PMCID: PMC3258718.10)Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors:clinical applications. Dis Markers. 2013; 35(6):727-34. doi: 10.1155/2013/726598.11)Cutolo M, Wilder RL. Different roles for androgens and estrogens in the susceptibility to autoimmunerheumatic diseases. Rheum Dis Clin North Am. 2000; 26(4): 825-39. doi: 10.1016/S0889-857X(05)70171-X. PMID: 11084946.12)da Silva JA. Relationships between glucocorticoids and gonadal steroids in rheumatoid arthritis. Ann N YAcad Sci. 2002; 966: 158-65. doi: 10.1111/j.1749-6632.2002.tb04212.x. PMID: 12114269.13)Cutolo M, Straub RH. Recent aspects of gonadal hormone and neurotransmitter interactions with synovialand immune cells: implications in rheumatoid arthritis. Ann Rheum Dis. 2000; 59(9): 657-61. doi:10.1136/ard.59.9.657. PMID: 10976076, PMCID: PMC1753272.14)Cutolo M, Straub RH. Insights into endocrine-immunological disturbances in autoimmunity and theirimpact on treatment. Arthritis Res Ther. 2009; 11(2): 218. doi: 10.1186/ar2630. PMID: 19435479, PMCID:PMC2688171.15)Cutolo M, Balleari E, Giusti M, Intra E, Accardo S. Androgenreplacement therapy in male patients withrheumatoid arthritis. Arthritis Rheum. 1991; 34(1): 1-5. doi: 10.1002/art.1780340102. PMID: 1824615.16)Oberbeck R, Kobbe P. Dehydroepiandrosterone (DHEA): a steroid with multiple effects. Is there anypossible optionin the treatment of critical illness? Curr Med Chem. 2010; 17(11): 1039-47. doi:10.2174/092986710790820570. PMID: 20156161.17)de la Torre B, Hedman M, Nilsson E, Olesen O, Thörner A. Relationship between blood and joint tissueDHEAS levels in rheumatoid arthritis and osteoarthritis. Clin Exp Rheumatol. 1993; 11(6): 597-601.PMID: 8299250.18)Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacementon endogenous inflammatory cytokines and lipid profiles in hypogonadalmen. J Clin Endocrinol Metab.2004; 89(7): 3313-8. doi: 10.1210/jc.2003-031069. PMID: 15240608.19)Rutkowski K, Sowa P, Rutkowska-Talipska J, Kuryliszyn-Moskal A, Rutkowski R.Dehydroepiandrosterone (DHEA): hypes and hopes. doi: 10.1007/s40265-014-0259-8. PMID: 25022952.20)Imrich R, Vigas M, Rovensky J, Aldag JC, Masi AT. Adrenal plasma steroid relations in glucocorticoid-naïve premenopausal rheumatoid arthritis patients during insulin-induced hypoglycemia test compared tomatched normal control females. EndocrRegul. 2009; 43(2): 65-73. PMID: 19856711.21)Voskuhl R. Sex differences in autoimmune diseases. Biol Sex Differ. 2011; 2(1): 1. doi: 10.1186/2042-6410-2-1. PMID: 21208397, PMCID: PMC3022636.
Bove R. Autoimmune diseases and reproductive aging. Clin Immunol.2013; 149(2): 251-64. doi:10.1016/j.clim.2013.02.010. PMID: 23522436, PMCID: PMC3805815.23)Cutolo M. Sex hormone adjuvant therapy in rheumatoid arthritis. Rheum Dis Clin North Am. 2000; 26(4):881-95. doi: 10.1016/S0889-857X(05)70174-5. PMID: 11084949.24)Dessein PH, Joffe BI, Stanwix AE, Moomal Z. Hyposecretion of the adrenal androgendehydroepiandrosterone sulfate and its relation to clinical variables in inflammatory arthritis. Arthritis Res.2001; 3(3): 183-8. doi: 10.1186/ar296. PMID: 11299059, PMCID: PMC30711.25)Kasper, Dennis L. Harrison’s principles of internal medicine. 19th Edition. 2015: 2136-49.26)Gordon D, Beastall GH, Thomson JA, Sturrock RD. Prolonged hypogonadism in male patients withrheumatoid arthritis during flares in disease activity. Br J Rheumatol. 1988; 27(6): 440-4. doi:10.1093/rheumatology/27.6.440. PMID: 3144408.27)Lunenfeld B, Mskhalaya G, Zitzmann M, Arver S, Kalinchenko S, Tishova Y, et al. Recommendations onthe diagnosis, treatment and monitoring of hypogonadism in men. Aging Male. 2015; 18(1): 5-15. doi:10.3109/13685538.2015.1004049. PMID: 25657080, PMCID: PMC4648196.28)Pikwer M, Giwercman A, Bergström U, Nilsson JÅ, Jacobsson LT, Turesson C. Association betweentestosterone levels and risk of future rheumatoid arthritis in men: a population-based case-control study.Ann Rheum Dis. 2014; 73(3): 573-9. doi: 10.1136/annrheumdis-2012-202781. PMID: 23553100.29)Masi AT, Elmore KB, Rehman AA, Chatterton RT, Goertzen NJ, Aldag JC. Lower SerumAndrostenedione Levels in Pre-Rheumatoid Arthritis versus Normal Control Women: Correlations withLower Serum Cortisol Levels. Autoimmune Dis. 2013; 2013: 593493. doi: 10.1155/2013/593493.30)Tengstrand B, Carlström K, Hafström I. Gonadal hormones in men with rheumatoid arthritis--from onsetthrough 2 years. J Rheumatol. 2009; 36(5): 887-92. doi: 10.3899/jrheum.080558. PMID: 19273455.31)Geenen R, Van Middendorp H, Bijlsma JW. The impact of stressors on health status and hypothalamic-pituitary-adrenal axis and autonomic nervous system responsiveness in rheumatoid arthritis. Ann N Y AcadSci. 2006; 1069: 77-97. doi: 10.1196/annals.1351.007. PMID: 16855136.32)Bird MD, Karavitis J, Kovacs EJ. Sex differences and estrogen modulation of the cellular immune responseafter injury. Cell Immunol. 2008; 252(1-2): 57-67. doi: 10.1016/j.cellimm.2007.09.007. PMID: 18294625PMCID: PMC2544631.33)Gilliver SC. Sex steroids as inflammatory regulators. J Steroid Biochem Mol Biol. 2010; 120(2-3): 105-15.doi: 10.1016/j.jsbmb.2009.12.015. PMID: 20045727.34)Hall GM, Larbre JP, Spector TD, PerryLA, Da Silva JA. A randomized trial of testosterone therapy inmales with rheumatoid arthritis. Br J Rheumatol. 1996; 35(6): 568-73. doi:10.1093/rheumatology/35.6.568. PMID: 8670579.35)Cutolo M, Sulli A, Capellino S, Villaggio B, Montagna P, Pizzorni C, etal. Anti-TNF and sex hormones.Ann N Y Acad Sci. 2006; 1069: 391-400. doi: 10.1196/annals.1351.037. PMID: 16855166.36)Karlson EW, Chibnik LB, McGrath M, Chang SC, Keenan BT, Costenbader KH, et al. A prospective studyof androgen levels, hormone-related genesand risk of rheumatoid arthritis. Arthritis Res Ther. 2009; 11(3):R97. doi: 10.1186/ar2742. PMID: 19555469, PMCID: PMC2714153.37)Banu J. Causes, consequences, and treatment of osteoporosis in men. Drug Des Devel Ther. 2013; 7: 849-60. doi: 10.2147/DDDT.S46101. PMID: 24009413, PMCID: PMC3758213.
Published
Issue
Section
License
Copyright (c) 2020 Knowledge Kingdom Publishing
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
