Abstract
Androgen deprivation therapy (ADT) plays an important role in managing prostate cancer. However, ADT may result in major cardiovascular events and potentially lead to fatal consequences. Cardiovascular disease is the leading cause of mortality and it is a very important health condition to look into. Asians and Caucasians differ both physiologically and genetically, and they may have display different cardiovascular profiles. In this article, we reviewed the literature focusing on the cardiovascular risk after ADT for prostate cancer in the Asian population. We would discuss about the pathogenesis of ADT leading to cardiovascular events, summarize the findings concerning cardiac and stroke risks after ADT, compare between the different modalities of ADT and also provide genetic basics which are unique to Asians. We hope this article would provide more insights into the cardiovascular risk after ADT for prostate cancer in an Asian perspective.
Similar content being viewed by others
References
Huggins C, Hodges CV (2002) Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol 168:9–12
Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G et al (2006) Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol 7:472–479
Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO et al (2002) Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 360:103–106
Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G et al (1997) Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med 337:295–300
D’Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW (2004) 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA 292:821–827
Sharifi N, Gulley JL, Dahut WL (2005) Androgen deprivation therapy for prostate cancer. JAMA 294:238–244
Hellerstedt BA, Pienta KJ (2002) The current state of hormonal therapy for prostate cancer. CA Cancer J Clin 52:154–179
Keating NL, O’Malley AJ, Smith MR (2006) Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 24:4448–4456
Lage MJ, Barber BL, Markus RA (2007) Association between androgen-deprivation therapy and incidence of diabetes among males with prostate cancer. Urology 70:1104–1108
Lopez AM, Pena MA, Hernandez R, Val F, Martin B, Riancho JA (2005) Fracture risk in patients with prostate cancer on androgen deprivation therapy. Osteoporos Int 16:707–711
Azoulay L, Yin H, Benayoun S, Renoux C, Boivin JF, Suissa S (2011) Androgen-deprivation therapy and the risk of stroke in patients with prostate cancer. Eur Urol 60:1244–1250
Ohira T, Iso H (2013) Cardiovascular disease epidemiology in Asia: an overview. Circ J 77:1646–1652
Collins L, Mohammed N, Ahmad T, Basaria S (2012) Androgen deprivation therapy for prostate cancer: implications for cardiometabolic clinical care. J Endocrinol Invest 35:332–339
Saylor PJ, Smith MR (2009) Metabolic complications of androgen deprivation therapy for prostate cancer. J Urol 181:1998–2006 (discussion 7–8)
Traish AM, Saad F, Guay A (2009) The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl 30:23–32
Scragg JL, Jones RD, Channer KS, Jones TH, Peers C (2004) Testosterone is a potent inhibitor of L-type Ca(2+) channels. Biochem Biophys Res Commun 318:503–506
Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH et al (2004) Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart 90:871–876
Dong F, Skinner DC, Wu TJ, Ren J (2011) The heart: a novel gonadotrophin-releasing hormone target. J Neuroendocrinol 23:456–463
Radu A, Pichon C, Camparo P, Antoine M, Allory Y, Couvelard A et al (2010) Expression of follicle-stimulating hormone receptor in tumor blood vessels. N Engl J Med 363:1621–1630
Albertsen PC, Klotz L, Tombal B, Grady J, Olesen TK, Nilsson J (2014) Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur Urol 65:565–573
Teoh JY, Chan SY, Chiu PK, Poon DM, Cheung HY, Hou SS et al (2015) Risk of acute myocardial infarction after androgen-deprivation therapy for prostate cancer in a Chinese population. BJU Int 116:382–387
Teoh JY, Chiu PK, Chan SY, Mak VM, Poon DM, Cheung HY et al (2016) Androgen deprivation therapy and the risk of acute myocardial infarction in Chinese men with prostate cancer. BJU Int 117(Suppl 1):2
Huang G, Yeung CY, Lee KK, Liu J, Ho KL, Yiu MK et al (2014) Androgen deprivation therapy and cardiovascular risk in chinese patients with nonmetastatic carcinoma of prostate. J Oncol 2014:529468
Akaza H (2010) Future prospects for luteinizing hormone-releasing hormone analogues in prostate cancer treatment. Pharmacology 85:110–120
Wang LH, Liu CK, Chen CH, Kao LT, Lin HC, Huang CY (2016) No increased risk of coronary heart disease for patients receiving androgen deprivation therapy for prostate cancer in Chinese/Taiwanese men. Andrology 4:128–132
Teoh JY, Chiu PK, Chan SY, Poon DM, Cheung HY, Hou SS et al (2015) Risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population living in Hong Kong. Jpn J Clin Oncol 45:483–487
Chung SD, Chen YK, Wu FJ, Lin HC (2012) Hormone therapy for prostate cancer and the risk of stroke: a 5-year follow-up study. BJU Int 109:1001–1005
Van Hemelrijck M, Garmo H, Holmberg L, Ingelsson E, Bratt O, Bill-Axelson A et al (2010) Absolute and relative risk of cardiovascular disease in men with prostate cancer: results from the Population-Based PCBaSe Sweden. J Clin Oncol 28:3448–3456
Jespersen CG, Norgaard M, Borre M (2014) Androgen-deprivation therapy in treatment of prostate cancer and risk of myocardial infarction and stroke: a nationwide Danish population-based cohort study. Eur Urol 65:704–709
Keating NL, O’Malley AJ, Freedland SJ, Smith MR (2010) Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst 102:39–46
Gandaglia G, Sun M, Popa I, Schiffmann J, Abdollah F, Trinh QD et al (2014) The impact of androgen-deprivation therapy (ADT) on the risk of cardiovascular (CV) events in patients with non-metastatic prostate cancer: a population-based study. BJU Int 114:E82–E89
Teoh JY, Chan SY, Chiu PK, Poon DM, Cheung HY, Hou SS et al (2015) Risk of cardiovascular thrombotic events after surgical castration versus gonadotropin-releasing hormone agonists in Chinese men with prostate cancer. Asian J Androl 17:493–496
Zaitsu M, Yamanoi M, Mikami K, Takeshima Y, Okamoto N, Imao S et al (2012) Surgical castration in hormone-refractory metastatic prostate cancer patients can be an alternative for medical castration. Adv Urol 2012:979154
Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P et al (2008) The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int 102:1531–1538
Ozono S, Ueda T, Hoshi S, Yamaguchi A, Maeda H, Fukuyama Y et al (2012) The efficacy and safety of degarelix, a GnRH antagonist: a 12-month, multicentre, randomized, maintenance dose-finding phase II study in Japanese patients with prostate cancer. Jpn J Clin Oncol 42:477–484
You D, Chung BH, Lee SE, Kim CS (2015) Efficacy and safety of degarelix in Korean patients with prostate cancer requiring androgen deprivation therapy: Open-label multicenter phase III study. Prostate Int 3:22–26
Li J, Mercer E, Gou X, Lu YJ (2013) Ethnical disparities of prostate cancer predisposition: genetic polymorphisms in androgen-related genes. Am J Cancer Res 3:127–151
Hsing AW, Gao YT, Wu G, Wang X, Deng J, Chen YL et al (2000) Polymorphic CAG and GGN repeat lengths in the androgen receptor gene and prostate cancer risk: a population-based case-control study in China. Cancer Res 60:5111–5116
Stanford JL, Just JJ, Gibbs M, Wicklund KG, Neal CL, Blumenstein BA et al (1997) Polymorphic repeats in the androgen receptor gene: molecular markers of prostate cancer risk. Cancer Res 57:1194–1198
Giovannucci E, Stampfer MJ, Krithivas K, Brown M, Dahl D, Brufsky A et al (1997) The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci U S A 94:3320–3323
Mohlig M, Arafat AM, Osterhoff MA, Isken F, Weickert MO, Spranger J et al (2011) Androgen receptor CAG repeat length polymorphism modifies the impact of testosterone on insulin sensitivity in men. Eur J Endocrinol 164:1013–1018
Nadeau G, Bellemare J, Audet-Walsh E, Flageole C, Huang SP, Bao BY et al (2011) Deletions of the androgen-metabolizing UGT2B genes have an effect on circulating steroid levels and biochemical recurrence after radical prostatectomy in localized prostate cancer. J Clin Endocrinol Metab 96:E1550–E1557
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None.
Rights and permissions
About this article
Cite this article
Teoh, J.Y.C., Ng, CF. Cardiovascular risk after androgen deprivation therapy for prostate cancer: an Asian perspective. Int Urol Nephrol 48, 1429–1435 (2016). https://doi.org/10.1007/s11255-016-1337-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11255-016-1337-5