Androgen deprivation therapy for prostate cancer and the risk of autoimmune diseases



Androgen deprivation therapy (ADT) has been a mainstay of treatment for advanced prostate cancer (PCa), but limited studies have been performed to investigate the association between ADT and autoimmune diseases.


We conducted a population-based nationwide cohort study of 17,168 patients newly diagnosed with PCa between 1996 and 2013 using the National Health Insurance Research Database (NHIRD) of Taiwan. Cox proportional hazards models with 1:1 propensity score-matched analysis were used to investigate the association between ADT use and the risk of autoimmune diseases. The autoimmune diseases included Graves’ disease, Crohn’s disease, psoriasis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, Guillain-Barre syndrome, Sjogren’s syndrome, myasthenia gravis, pernicious anemia, hereditary hemolytic anemia, polyarteritis nodosa, Celiac disease, uveitis, polymyalgia rheumatica, dermatomyositis, Hashimoto’s thyroiditis, hypersensitivity vasculitis, Behcet’s disease, polymyositis, alopecia areata, Wegener’s granulomatosis, ulcerative colitis, autoimmune hemolytic anemia, pemphigus, multiple sclerosis, systemic sclerosis, Goodpasture syndrome, giant cell arteritis, thromboangitis obliterans, arteritis obliterans, and Kawasaki disease. The duration of ADT use as a time-dependent variable was also examined for its association with autoimmune diseases. We also performed six secondary analyses.


Of the 17,168 selected PCa patients, 14,444 patients met all the inclusion and exclusion criteria. After propensity score matching, 5590 ADT users and 5590 non-ADT users were included in the study cohort. A propensity score-matched analysis (adjusted hazard ratio (aHR), 0.619, 95% confidence interval (CI), 0.51–0.75, P < 0.001) demonstrated a significantly decreased risk of autoimmune diseases in ADT users. A significant decrease in the risk of autoimmune diseases with increasing ADT duration was also demonstrated (P < 0.001).


We observed that ADT use in patients with PCa was associated with a decreased risk of autoimmune diseases. These novel findings provide a potential role for androgen deprivation therapy in the modification of inflammation and autoimmunity in Asian patients with prostate cancer.

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Fig. 1


  1. 1.

    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

    Article  Google Scholar 

  2. 2.

    Huggins C, Hodges CV. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin. 1972;22:232–40.

    CAS  Article  Google Scholar 

  3. 3.

    Cancer Registry Annual Report, 2000–2011. Taiwan: Department of Health, the Executive Yuan, Republic of China; 2003–13.

  4. 4.

    Shahani S, Braga-Basaria M, Basaria S. Androgen deprivation therapy in prostate cancer and metabolic risk for atherosclerosis. J Clin Endocrinol Metab. 2008;93:2042–9.

    Article  Google Scholar 

  5. 5.

    Fijak M, Meinhardt A. The testis in immune privilege. Immunol Rev. 2006;213:66–81.

    CAS  Article  Google Scholar 

  6. 6.

    Aragon-Ching JB, Williams KM, Gulley JL. Impact of androgen-deprivation therapy on the immune system: implications for combination therapy of prostate cancer. Front Biosci. 2007;12:4957–71.

    CAS  Article  Google Scholar 

  7. 7.

    Keating NL, O’Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006;24:4448–56.

    CAS  Article  Google Scholar 

  8. 8.

    Nead KT, Gaskin G, Chester C, et al. Androgen deprivation therapy and future Alzheimer’s disease risk. J Clin Oncol. 2016;34:566–71.

    CAS  Article  Google Scholar 

  9. 9.

    Klil-Drori AJ, Tascilar K, Yin H, Aprikian A, Bitton A, Azoulay L. Androgen deprivation therapy and the incidence of inflammatory bowel disease in patients with prostate cancer. Am J Epidemiol. 2016;184:15–22.

    Article  Google Scholar 

  10. 10.

    Kaczmarek P, Pokoca L, Niemirowicz J, Majewska E, Baj Z. Effect of luteinizing hormone-releasing hormone (LHRH) analogue treatment on a cytokine profile in prostate cancer patients. Pharmacol Rep. 2008;60:399–403.

    CAS  PubMed  Google Scholar 

  11. 11.

    Salman H, Bergman M, Blumberger N, Djaldetti M, Bessler H. Do androgen deprivation drugs affect the immune cross-talk between mononuclear and prostate cancer cells? Biomed Pharmacother. 2014;68:21–24.

    CAS  Article  Google Scholar 

  12. 12.

    Bureau of National Health Insurance DoH, Executive Yuan. The National Health Insurance Statistics. 2013. Accessed 18 Sep 2014.

  13. 13.

    Wu CY, Chen YJ, Ho HJ, Hsu YC, Kuo KN, Wu MS, et al. Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA. 2012;308:1906–14.

    CAS  Article  Google Scholar 

  14. 14.

    Liu JM, Chen TH, Chuang HC, Wu CT, Hsu RJ. Statin reduces the risk of dementia in diabetic patients receiving androgen deprivation therapy for prostate cancer. Prostate Cancer Prostatic Dis. 2018. [Epub ahead of print]

    Article  Google Scholar 

  15. 15.

    Chen SJ, Chao YL, Chen CY, Chang CM, Wu EC, Wu CS, et al. Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study. Br J Psychiatry. 2012;200:374–80.

    Article  Google Scholar 

  16. 16.

    Liu JM, Lin PH, Hsu RJ, Chang YH, Cheng KC, Pang ST, et al. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer. Medicine (Baltimore). 2016;95:e4475.

    Article  Google Scholar 

  17. 17.

    Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.

    Article  Google Scholar 

  18. 18.

    Frakt AB. An observational study goes where randomized clinical trials have not. JAMA. 2015;313:1091–2.

    Article  Google Scholar 

  19. 19.

    De Nunzio C, Kramer G, Marberger M, Montironi R, Nelson W, Schröder F, et al. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol. 2011;60:106–17.

    Article  Google Scholar 

  20. 20.

    Nelson WG, De Marzo AM, Isaacs WB. Prostate cancer. N Engl J Med. 2003;349:366–81.

    CAS  Article  Google Scholar 

  21. 21.

    Zandman-Goddard G, Peeva E. Gender and autoimmunity. Autoimmun Rev. 2007;6:366–72.

    CAS  Article  Google Scholar 

  22. 22.

    Morse MD, McNeel DG. Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses. Hum Immunol. 2012;71:496–504.

    Article  Google Scholar 

  23. 23.

    Saylor PJ, Kozak KR, Smith MR, Ancukiewicz MA, Efstathiou JA, Zietman AL, et al. Changes in biomarkers of inflammation and angiogenesis during androgen deprivation therapy for prostate cancer. Oncologist. 2012;17:212–9.

    CAS  Article  Google Scholar 

  24. 24.

    Nadiminty N, Lou W, Lee SO, Lin X, Trump DL, Gao AC. Stat3 activation of NF-{kappa}B p100 processing involves CBP/ p300-mediated acetylation. Proc Natl Acad Sci USA. 2006;103:7264–9.

    CAS  Article  Google Scholar 

  25. 25.

    Huang S, Pettaway CA, Uehara H, Bucana CD, Fidler IJ. Blockade of NF-kappaB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene. 2001;20:4188–97.

    CAS  Article  Google Scholar 

  26. 26.

    Guzmán-Soto I, Salinas E, Quintanar JL. Leuprolide acetate inhibits spinal cord inflammatory response in experimental autoimmune encephalomyelitis by suppressing NF-κB activation. Neuroimmunomodulation. 2016;23:33–40.

    Article  Google Scholar 

  27. 27.

    Lowes MA, Suarez-Farinas M, Krueger JG. Immunology of psoriasis. Annu Rev Immunol. 2014;32:227–55.

    CAS  Article  Google Scholar 

  28. 28.

    Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 2007;445:866–73.

    CAS  Article  Google Scholar 

  29. 29.

    Horai R, Caspi RR. Cytokines in autoimmune uveitis. J Interferon Cytokine Res. 2011;31:733–44.

    CAS  Article  Google Scholar 

  30. 30.

    Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmun Rev. 2015;14:174–80.

    CAS  Article  Google Scholar 

  31. 31.

    Engl T, Relja B, Blumenberg C, Müller I, Ringel EM, Beecken WD, et al. Prostate tumor CXC-chemokine profile correlates with cell adhesion to endothelium and extracellular matrix. Life Sci. 2006;78:1784–93.

    CAS  Article  Google Scholar 

  32. 32.

    Murphy C, McGurk M, Pettigrew J, Santinelli A, Mazzucchelli R, Johnston PG, et al. Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer. Clin Cancer Res. 2005;11:4117–27.

    CAS  Article  Google Scholar 

  33. 33.

    Taichman RS, Cooper C, Keller ET, Pienta KJ, Taichman NS, McCauley LK. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res. 2002;62:1832–7.

    CAS  PubMed  Google Scholar 

  34. 34.

    Shen H, Lentsch AB. Progressive dysregulation of transcription factors NF-kappa B and STAT1 in prostate cancer cells causes proangiogenic production of CXC chemokines. Am J Physiol Cell Physiol. 2004;286:C840–847.

    CAS  Article  Google Scholar 

  35. 35.

    Morse MD, McNeel DG. T cells localized to the androgen-deprived prostate are TH1 and TH17 biased. Prostate. 2012;72:1239–47.

    CAS  Article  Google Scholar 

  36. 36.

    Koh YT, Gray A, Higgins SA, Hubby B, Kast WM. Androgen ablation augments prostate cancer vaccine immunogenicity only when applied after immunization. Prostate. 2009;69:571–84.

    CAS  Article  Google Scholar 

  37. 37.

    Khosla S, Atkinson EJ, Dunstan CR, O’Fallon WM. Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men. J Clin Endocrinol Metab. 2002;87:1550–4.

    CAS  Article  Google Scholar 

  38. 38.

    Yang DD, Krasnova A, Nead KT, Choueiri TK, Hu JC, Hoffman KE, et al. Androgen deprivation therapy and risk of rheumatoid arthritis in patients with localized prostate cancer. Ann Oncol. 2018;29:386–91.

    CAS  Article  Google Scholar 

  39. 39.

    Kili-Drori A, Tascilar K, Yin H, Aprikian AG, Azoulay L. Androgen deprivation therapy and the incidence of autoimmune diseases. J Clin Oncol. 2015;33:e16010.

  40. 40.

    Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res. 2002;4:S265–272.

    Article  Google Scholar 

  41. 41.

    Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, et al. Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study. Eur J Endocrinol. 2011;164:801–9.

    Article  Google Scholar 

  42. 42.

    Teng W, Shan Z, Teng X, Guan H, Li Y, Teng D, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med. 2006;354:2783–93.

    CAS  Article  Google Scholar 

  43. 43.

    Bell LM, Sedlack R, Beard CM, Perry CO, Michet CJ, Kurland LT. Incidence of psoriasis in Rochester, Minn, 1980−1983. Arch Dermatol. 1991;127:1184–7.

    CAS  Article  Google Scholar 

  44. 44.

    Donker GA, Foets M, Spreeuwenberg P, van der Werf GT. Management of psoriasis in general practice now more in agreement with the guidelines of the Dutch College of General Practitioners (NHG). Ned Tijdschr Geneeskd. 1998;142:1379–83.

    CAS  PubMed  Google Scholar 

  45. 45.

    Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004;111:491–500.

    Article  Google Scholar 

  46. 46.

    Hwang DK, Chou YJ, Pu CY, Chou P. Epidemiology of uveitis among the Chinese population in Taiwan: a population-based study. Ophthalmology. 2012;119:2371–6.

    Article  Google Scholar 

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This study was supported by the Taoyuan General Hospital, Ministry of Health and Welfare (Grants No. 10602), the Tri-Service General Hospital (Grants No.TSGH-C105-168 and TSGH-C108-046), and the Ministry of Science and Technology Taiwan (Grants No. MOST 104-2320-B-016-012-MY3).

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Correspondence to Ren-Jun Hsu.

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Liu, JM., Yu, CP., Chuang, HC. et al. Androgen deprivation therapy for prostate cancer and the risk of autoimmune diseases. Prostate Cancer Prostatic Dis 22, 475–482 (2019).

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