Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Assessing the effects of prostate cancer therapies on cardiovascular health

Nature Reviews Urology volume 22, pages 509–525 (2025)Cite this article

Subjects

Abstract

Contemporary advances in prostate cancer treatments have markedly improved patient outcomes, yet concerns persist regarding the increased cardiovascular toxicity of prostate cancer treatments, which is multifaceted. Local therapies entail non-negligible cardiovascular risks. The effects of androgen deprivation therapy, which is pivotal in disease management, on cardiovascular health remains contentious, with gonadotropin-releasing hormone agonists and antagonists showing varying cardiovascular outcomes. Despite the ongoing controversy over the cardiovascular risks of gonadotropin-releasing hormone antagonists versus agonists, current evidence does not support favouring one over the other based solely on cardiovascular risk. Combination therapy with androgen receptor pathway inhibitors and androgen deprivation therapy shows additive cardiovascular risks, but robust comparative data are lacking. Chemotherapies such as docetaxel and cabazitaxel, along with emerging targeted therapies and radiopharmaceuticals, are associated with varied cardiovascular risks, necessitating personalized patient assessment. Clinicians should adhere to cardio-oncology guidelines when prescribing therapeutic agents, especially for patients with pre-existing cardiovascular conditions. Optimal monitoring and management strategies are essential to mitigate cardiovascular morbidity and mortality.

Key points

  • Prostate cancer treatments, although effective, have been associated with increased risks of cardiovascular toxicity, necessitating careful evaluation of patient profiles before initiating treatments.

  • Despite much debate, the current best available data do not show an advantage of gonadotropin-releasing hormone antagonists over agonists.

  • Combination therapies, such as androgen deprivation therapy and androgen receptor axis-targeted therapies, are associated with additive cardiovascular risks, emphasizing the need for vigilant monitoring and adherence to cardio-oncology guidelines, particularly for patients with pre-existing cardiovascular comorbidities.

  • Robust cardio-oncology strategies incorporating improved risk assessment tools and multidisciplinary patient management might minimize cardiovascular morbidity and mortality.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Hormonal axis and cardiovascular effects of prostate cancer therapies.

Similar content being viewed by others

References

  1. Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 72, 7–33 (2022).

    Google Scholar 

  2. Bill-Axelson, A. et al. Radical prostatectomy or watchful waiting in early prostate cancer. N. Engl. J. Med. 370, 932–942 (2014).

    Article  CAS  Google Scholar 

  3. Dearnaley, D. P. et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol. 8, 475–487 (2007).

    Article  Google Scholar 

  4. Loblaw, D. A. et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J. Clin. Oncol. 25, 1596–1605 (2007).

    Article  CAS  Google Scholar 

  5. Sartor, O. et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 15, 738–46 (2014).

    Article  CAS  Google Scholar 

  6. Petrylak, D. P. et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N. Engl. J. Med. 351, 1513–1520 (2004).

    Article  CAS  Google Scholar 

  7. Beer T. M. et al. Enzalutamide in metastatic prostate cancer before chemotherapy. J. Clin. Oncol. 37, 2974–2986 (2019).

    Google Scholar 

  8. de Bono, J. S. et al. Abiraterone and increased survival in metastatic prostate cancer. N. Engl. J. Med. 364, 1995–2005 (2011).

    Article  Google Scholar 

  9. Clark, R., Vesprini, D. & Narod, S. A. The effect of age on prostate cancer survival. Cancers 14, 4149 (2022).

    Article  Google Scholar 

  10. Sturgeon, K. M. et al. A population-based study of cardiovascular disease mortality risk in US cancer patients. Eur. Heart J. 40, 3889–3897 (2019).

    Article  Google Scholar 

  11. Epstein, M. M., Edgren, G., Rider, J. R., Mucci, L. A. & Adami, H.-O. Temporal trends in cause of death among Swedish and US men with prostate cancer. J. Natl Cancer Inst. 104, 1335–1342 (2012).

    Article  Google Scholar 

  12. Van Hemelrijck, M. et al. 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 (2010).

    Article  Google Scholar 

  13. Leong, D. P. et al. Cardiovascular risk in men with prostate cancer: insights from the RADICAL PC Study. J. Urol. 203, 1109–1111 (2020).

    Article  Google Scholar 

  14. Wilk, M., Waśko-Grabowska, A. & Szmit, S. Cardiovascular complications of prostate cancer treatment. Front. Pharmacol. 11, 555475 (2020).

    Article  CAS  Google Scholar 

  15. Rawla, P. Epidemiology of prostate cancer. World J. Oncol. 10, 63–89 (2019).

    Article  CAS  Google Scholar 

  16. Schoormans, D. et al. Incidence of cardiovascular disease up to 13 year after cancer diagnosis: a matched cohort study among 32 757 cancer survivors. Cancer Med. 7, 4952–4963 (2018).

    Article  CAS  Google Scholar 

  17. Zhang, X. et al. Ten-year cardiovascular risk among cancer survivors: the National Health and Nutrition Examination Survey. PLoS ONE 16, e0247919 (2021).

    Article  CAS  Google Scholar 

  18. Marques, P. et al. Physiology of GnRH and gonadotrophin secretion. Endotext [Internet] https://www.ncbi.nlm.nih.gov/books/NBK279070/ (updated 15 October 2024).

  19. Keating, N. L., O’Malley, A. J., Freedland, S. J. & Smith, M. R. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J. Natl Cancer Inst. 102, 39–46 (2010).

    Article  CAS  Google Scholar 

  20. Saigal, C. S. et al. Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer. Cancer 110, 1493–1500 (2007).

    Article  CAS  Google Scholar 

  21. Tsai, H. K., D’Amico, A. V., Sadetsky, N., Chen, M.-H. & Carroll, P. R. Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. J. Natl Cancer Inst. 99, 1516–1524 (2007).

    Article  Google Scholar 

  22. Levine, G. N. et al. Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. Circulation 121, 833–840 (2010).

    Article  Google Scholar 

  23. Research Center for Drug Evaluation. FDA drug safety communication: update to ongoing safety review of GnRH agonists and notification to manufacturers of GnRH agonists to add new safety information to labeling regarding increased risk of diabetes and certain cardiovascular diseases (FDA, 2017).

  24. Smith, M. R., Klotz, L., Persson, B.-E., Olesen, T. K. & Wilde, A. A. M. Cardiovascular safety of degarelix: results from a 12-month, comparative, randomized, open label, parallel group phase III trial in patients with prostate cancer. J. Urol. 184, 2313–2319 (2010).

    Article  CAS  Google Scholar 

  25. Butler, S. S. et al. Risk of cardiovascular mortality with androgen deprivation therapy in prostate cancer: a secondary analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Randomized Controlled Trial. Cancer 127, 2213–2221 (2021).

    Article  CAS  Google Scholar 

  26. Kim, D. K. et al. Does androgen-deprivation therapy increase the risk of ischemic cardiovascular and cerebrovascular diseases in patients with prostate cancer? A nationwide population-based cohort study. J. Cancer Res. Clin. Oncol. 147, 1217–1226 (2021).

    Article  CAS  Google Scholar 

  27. Nguyen, P. L. et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA 306, 2359–2366 (2011).

    Article  CAS  Google Scholar 

  28. Holmes, J. A. et al. Cardiovascular preventive care and coordination of care in prostate cancer survivors: a multi-institutional prospective study. Int. J. Radiat. Oncol. Biol. Phys. 103, 112–115 (2019).

    Article  Google Scholar 

  29. Saylor, P. J. & Fogerty, A. E. Prostate-cancer-associated hypercoagulability: do we need to worry about androgen deprivation? Lancet Oncol. 11, 406–407 (2010).

    Article  Google Scholar 

  30. Smith, M. R. et al. Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer. Cancer 112, 2188–2194 (2008).

    Article  CAS  Google Scholar 

  31. Smith, M. R., Lee, H. & Nathan, D. M. Insulin sensitivity during combined androgen blockade for prostate cancer. J. Clin. Endocrinol. Metab. 91, 1305–1308 (2006).

    Article  CAS  Google Scholar 

  32. Cannon, J. G., Kraj, B. & Sloan, G. Follicle-stimulating hormone promotes RANK expression on human monocytes. Cytokine 53, 141–144 (2011).

    Article  CAS  Google Scholar 

  33. Smith, J. C. et al. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J. Clin. Endocrinol. Metab. 86, 4261–4267 (2001).

    Article  CAS  Google Scholar 

  34. Bosco, C. et al. Quantifying observational evidence for risk of fatal and nonfatal cardiovascular disease following androgen deprivation therapy for prostate cancer: a meta-analysis. Eur. Urol. 68, 386–396 (2015).

    Article  Google Scholar 

  35. Gagliano-Jucá, T. et al. Androgen deprivation therapy is associated with prolongation of QTc interval in men with prostate cancer. J. Endocr. Soc. 2, 485–496 (2018).

    Article  Google Scholar 

  36. Bourghardt, J. et al. Androgen receptor-dependent and independent atheroprotection by testosterone in male mice. Endocrinology 151, 5428–5437 (2010).

    Article  CAS  Google Scholar 

  37. Takov, K., Wu, J., Denvir, M. A., Smith, L. B. & Hadoke, P. W. F. The role of androgen receptors in atherosclerosis. Mol. Cell. Endocrinol. 465, 82–91 (2018).

    Article  CAS  Google Scholar 

  38. Hopmans, S. N., Duivenvoorden, W. C. M., Werstuck, G. H., Klotz, L. & Pinthus, J. H. GnRH antagonist associates with less adiposity and reduced characteristics of metabolic syndrome and atherosclerosis compared with orchiectomy and GnRH agonist in a preclinical mouse model. Urol. Oncol. 32, 1126–1134 (2014).

    Article  CAS  Google Scholar 

  39. Knutsson, A. et al. Treatment with a GnRH receptor agonist, but not the GnRH receptor antagonist degarelix, induces atherosclerotic plaque instability in ApoE−/− mice. Sci. Rep. 6, 26220 (2016).

    Article  CAS  Google Scholar 

  40. Wang, Q. et al. FSH is responsible for androgen deprivation therapy-associated atherosclerosis in mice by exaggerating endothelial inflammation and monocyte adhesion. Arteriosclerosis Thrombosis Vasc. Biol. 44, 698–719 (2024).

    Article  CAS  Google Scholar 

  41. Poljak, Z., Hulin, I., Maruscakova, L. & Mladosievicova, B. Are GnRH and FSH potentially damaging factors in the cardiovascular system? Pharmazie 73, 187–190 (2018).

    CAS  Google Scholar 

  42. Sun, L. et al. Further evidence for direct pro-resorptive actions of FSH. Biochem. Biophys. Res. Commun. 394, 6–11 (2010).

    Article  CAS  Google Scholar 

  43. Crawford, E. D. et al. The potential role of follicle-stimulating hormone in the cardiovascular, metabolic, skeletal, and cognitive effects associated with androgen deprivation therapy. Urol. Oncol. 35, 183–191 (2017).

    Article  CAS  Google Scholar 

  44. Mohammed, K. et al. Oral vs transdermal estrogen therapy and vascular events: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 100, 4012–4020 (2015).

    Article  CAS  Google Scholar 

  45. Russell, N. et al. Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial. Eur. J. Endocrinol. 178, 565–576 (2018).

    Article  CAS  Google Scholar 

  46. Langley, R. E. et al. Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. Lancet 397, 581 (2021).

    Article  CAS  Google Scholar 

  47. Anderson, J. et al. Degarelix versus goserelin (+ antiandrogen flare protection) in the relief of lower urinary tract symptoms secondary to prostate cancer: results from a phase IIIb study (NCT00831233). Urol. Int. 90, 321–328 (2012).

    Article  Google Scholar 

  48. Mason, M. et al. Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide. Clin. Oncol. 25, 190–196 (2013).

    Article  CAS  Google Scholar 

  49. Axcrona, K. et al. Androgen deprivation therapy for volume reduction, lower urinary tract symptom relief and quality of life improvement in patients with prostate cancer: degarelix vs goserelin plus bicalutamide. BJU Int. 110, 1721–1728 (2012).

    Article  CAS  Google Scholar 

  50. Tombal, B. et al. P109 Efficacy and safety of a 3-monthly depot formulation of degarelix compared with goserelin in prostate cancer. Eur. Urol. Suppl. 5, 228 (2012).

    Article  Google Scholar 

  51. Crawford, D., Shore, N., Higano, C., Neijber, A. & Yankov, V. PD27-05 Intermittent androgen deprivation with the gonadotrophin-releasing hormone antagonist degarelix. J. Urol. 191, e766 (2014).

    Article  Google Scholar 

  52. Albertsen, P. C. et al. Cardiovascular morbidity associated with gonadotropin releasing hormone agonists and an antagonist. Eur. Urol. 65, 565–573 (2014).

    Article  CAS  Google Scholar 

  53. Abufaraj, M. et al. Differential impact of gonadotropin-releasing hormone antagonist versus agonist on clinical safety and oncologic outcomes on patients with metastatic prostate cancer: a meta-analysis of randomized controlled trials. Eur. Urol. 79, 44–53 (2021).

    Article  CAS  Google Scholar 

  54. Sciarra, A. et al. A meta-analysis and systematic review of randomized controlled trials with degarelix versus gonadotropin-releasing hormone agonists for advanced prostate cancer. Medicine 95, e3845 (2016).

    Article  CAS  Google Scholar 

  55. Scailteux, L.-M., Naudet, F., Alimi, Q., Vincendeau, S. & Oger, E. Mortality, cardiovascular risk, and androgen deprivation therapy for prostate cancer: a systematic review with direct and network meta-analyses of randomized controlled trials and observational studies. Medicine 95, e3873 (2016).

  56. Ma, C. et al. Comparing the risk of cardiovascular disease following GnRH agonist and GnRH antagonist therapy for patient with prostate cancer: a systematic review and meta-analysis. Minerva Urol. Nephrol. 73, 276–282 (2021).

    Article  Google Scholar 

  57. Cirne, F. et al. The cardiovascular effects of gonadotropin-releasing hormone antagonists in men with prostate cancer. Eur. Heart J. Cardiovasc. Pharmacother. 8, 253–262 (2021).

    Article  Google Scholar 

  58. Shore, N. D. et al. Oral relugolix for androgen-deprivation therapy in advanced prostate cancer. N. Engl. J. Med. 382, 2187–2196 (2020).

    Article  CAS  Google Scholar 

  59. Sari Motlagh, R. et al. The efficacy and safety of relugolix compared with degarelix in advanced prostate cancer patients: a network meta-analysis of randomized trials. Eur. Urol. Oncol. 5, 138–145 (2021).

    Article  Google Scholar 

  60. Davey, P. & Kirby, M. G. Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice. World J. Urol. 39, 307–315 (2021).

    Article  CAS  Google Scholar 

  61. Perrone, V. et al. Cardiovascular risk profile in prostate cancer patients treated with GnRH agonists versus antagonists: an Italian real-world analysis. Ther. Clin. Risk Manag. 16, 393–401 (2020).

    Article  CAS  Google Scholar 

  62. Scailteux, L.-M. et al. Androgen deprivation therapy and cardiovascular risk: no meaningful difference between GnRH antagonist and agonists — a nationwide population-based cohort study based on 2010–2013 French Health Insurance data. Eur. J. Cancer 77, 99–108 (2017).

    Article  CAS  Google Scholar 

  63. George, G. et al. Risk of cardiovascular disease following gonadotropin‐releasing hormone agonists vs antagonists in prostate cancer: real‐world evidence from five databases. Int. J. Cancer 148, 2203–2211 (2021).

    Article  CAS  Google Scholar 

  64. Cardwell, C. R. et al. The risk of cardiovascular disease in prostate cancer patients receiving androgen deprivation therapies. Epidemiology 31, 432–440 (2020).

    Article  Google Scholar 

  65. Hupe, M. C. et al. Retrospective analysis of patients with prostate cancer initiating GnRH agonists/antagonists therapy using a German claims database: epidemiological and patient outcomes. Front. Oncol. 8, 543 (2018).

    Article  Google Scholar 

  66. Wallach, J. D. et al. Real-world cardiovascular outcomes associated with degarelix vs leuprolide for prostate cancer treatment. JAMA Netw. Open 4, e2130587 (2021).

    Article  Google Scholar 

  67. Lopes, R. D. et al. Cardiovascular safety of degarelix versus leuprolide in patients with prostate cancer: the primary results of the PRONOUNCE randomized trial. Circulation 144, 1295–1307 (2021).

    Article  Google Scholar 

  68. Sun, Y. et al. Efficacy and safety of degarelix in patients with prostate cancer: results from a phase III study in China. Asian J. Urol. 7, 301–308 (2020).

    Article  Google Scholar 

  69. Ozono, S. et al. 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 (2012).

    Article  Google Scholar 

  70. Ozono, S. et al. Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: a phase III study. Cancer Sci. 109, 1920–1929 (2018).

    Article  CAS  Google Scholar 

  71. Margel, D. et al. Cardiovascular morbidity in a randomized trial comparing GnRH agonist and GnRH antagonist among patients with advanced prostate cancer and preexisting cardiovascular disease. J. Urol. 202, 1199–1208 (2019).

    Article  Google Scholar 

  72. Rehman, Y. & Rosenberg, J. E. Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer. Drug. Des. Devel Ther. 6, 13–18 (2012).

    Article  CAS  Google Scholar 

  73. Schalken, J. & Fitzpatrick, J. M. Enzalutamide: targeting the androgen signalling pathway in metastatic castration‐resistant prostate cancer. BJU Int. 117, 215–225 (2016).

    Article  CAS  Google Scholar 

  74. Patel, U. J. & Caulfield, S. Apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer. J. Adv. Pract. Oncol. 10, 501–507 (2019).

    Google Scholar 

  75. Fizazi, K., Smith, M. R. & Tombal, B. Clinical development of darolutamide: a novel androgen receptor antagonist for the treatment of prostate cancer. Clin. Genitourin. Cancer 16, 332–340 (2018).

    Article  Google Scholar 

  76. Morgans, A. K. et al. Androgen receptor inhibitor treatments: cardiovascular adverse events and comorbidity considerations in patients with non-metastatic prostate cancer. Urol. Oncol. 39, 52–62 (2021).

    Article  CAS  Google Scholar 

  77. Fradin, J., Kim, F. J., Lu-Yao, G. L., Storozynsky, E. & Kelly, W. K. Review of cardiovascular risk of androgen deprivation therapy and the influence of race in men with prostate cancer. Cancers 15, 2316 (2023).

    Article  CAS  Google Scholar 

  78. Cone, E. B. et al. Cardiovascular toxicities associated with abiraterone compared to enzalutamide — a pharmacovigilance study. EClinicalMedicine 36, 100887 (2021).

    Article  Google Scholar 

  79. Lee, Y. H. A. et al. Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study. Prostate Cancer Prostatic Dis. 27, 776–782 (2023).

    Article  Google Scholar 

  80. Hu, J., Aprikian, A. G., Vanhuyse, M. & Dragomir, A. Comparative cardiovascular safety of novel hormonal agents in metastatic castration-resistant prostate cancer using real-world data. Clin. Genitourin. Cancer 20, 17–24 (2022).

    Article  Google Scholar 

  81. Matsukawa, A. et al. Cardiovascular events among men with prostate cancer treated with androgen receptor signaling inhibitors: a systematic review, meta-analysis, and network meta-analysis. Prostate Cancer Prostatic Dis. https://doi.org/10.1038/s41391-024-00886-0 (2024).

  82. Kwon, W.-A., Song, Y. S. & Lee, M.-K. Strategic advances in combination therapy for metastatic castration-sensitive prostate cancer: current insights and future perspectives. Cancers 16, 3187 (2024).

    Article  CAS  Google Scholar 

  83. Cohagan, B. & Brandis, D. Torsade de Pointes. StatPearls [Internet] https://www.ncbi.nlm.nih.gov/books/NBK459388/ (updated 8 August 2023).

  84. Verzoni, E. et al. Safety of long-term exposure to abiraterone acetate in patients with castration-resistant prostate cancer and concomitant cardiovascular risk factors. Ther. Adv. Med. Oncol. 8, 323–330 (2016).

    Article  CAS  Google Scholar 

  85. Iacovelli, R. et al. The cardiovascular toxicity of abiraterone and enzalutamide in prostate cancer. Clin. Genitourin. Cancer 16, e645–e653 (2018).

    Article  Google Scholar 

  86. Di Nunno, V. et al. New hormonal agents in patients with nonmetastatic castration-resistant prostate cancer: meta-analysis of efficacy and safety outcomes. Clin. Genitourin. Cancer 17, e871–e877 (2019).

    Article  Google Scholar 

  87. El-Taji, O. et al. Cardiovascular events and androgen receptor signaling inhibitors in advanced prostate cancer: a systematic review and meta-analysis. JAMA Oncol. 10, 874–884 (2024).

    Article  Google Scholar 

  88. Zhou, S. et al. Cardiovascular toxicity associated with androgen receptor axis-targeted agents in patients with prostate cancer: a meta-analysis of randomized controlled trials. Clin. Genitourin. Cancer 22, 102066 (2024).

    Article  Google Scholar 

  89. Cao, B., Kim, M., Reizine, N. M. & Moreira, D. M. Adverse events and androgen receptor signaling inhibitors in the treatment of prostate cancer: a systematic review and multivariate network meta-analysis. Eur. Urol. Oncol. 6, 237–250 (2023).

    Article  Google Scholar 

  90. Smith, M. R. et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N. Engl. J. Med. 378, 1408–1418 (2018).

    Article  CAS  Google Scholar 

  91. Chi, K. N. et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N. Engl. J. Med. 381, 13–24 (2019).

    Article  CAS  Google Scholar 

  92. Fizazi, K. et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N. Engl. J. Med. 380, 1235–1246 (2019).

    Article  CAS  Google Scholar 

  93. Freedland, S. J. et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N. Engl. J. Med. 389, 1453–1465 (2023).

    Article  CAS  Google Scholar 

  94. Stein, M. N., Goodin, S. & DiPaola, R. S. Abiraterone in prostate cancer: a new angle to an old problem. Clin. Cancer Res. 18, 1848–1854 (2012).

    Article  CAS  Google Scholar 

  95. Dean, L. & Kane, M. in Medical Genetics Summaries (eds Pratt, V. M. et al.) (National Center for Biotechnology Information (US), 2012).

  96. Monbaliu, J. et al. In vitro and in vivo drug–drug interaction studies to assess the effect of abiraterone acetate, abiraterone, and metabolites of abiraterone on CYP2C8 activity. Drug. Metab. Dispos. 44, 1682–1691 (2016).

    Article  CAS  Google Scholar 

  97. Gibbons, J. A. et al. Pharmacokinetic drug interaction studies with enzalutamide. Clin. Pharmacokinet. 54, 1057–1069 (2015).

    Article  CAS  Google Scholar 

  98. Duran, I. et al. Pharmacokinetic drug–drug interaction of apalutamide, part 1: clinical studies in healthy men and patients with castration-resistant prostate cancer. Clin. Pharmacokinet. 59, 1135–1148 (2020).

    Article  CAS  Google Scholar 

  99. Zurth, C. et al. Drug–drug interaction potential of darolutamide: in vitro and clinical studies. Eur. J. Drug. Metab. Pharmacokinet. 44, 747–759 (2019).

    Article  CAS  Google Scholar 

  100. Bolek, H. et al. Androgen receptor pathway inhibitors and drug–drug interactions in prostate cancer. ESMO Open 9, 103736 (2024).

    Article  CAS  Google Scholar 

  101. Meng, F. et al. Stroke related to androgen deprivation therapy for prostate cancer: a meta-analysis and systematic review. BMC Cancer 16, 180 (2016).

    Article  Google Scholar 

  102. Zhao, J. et al. Androgen deprivation therapy for prostate cancer is associated with cardiovascular morbidity and mortality: a meta-analysis of population-based observational studies. PLoS ONE 9, e107516 (2014).

    Article  Google Scholar 

  103. Barker, S. J., Gamel, D. M. & Tremper, K. K. Cardiovascular effects of anesthesia and operation. Crit. Care Clin. 3, 251–268 (1987).

    Article  CAS  Google Scholar 

  104. Committee Members et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery — executive summary a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to update the 1996 guidelines on perioperative cardiovascular evaluation for noncardiac surgery). Circulation 105, 1257–1267 (2002).

    Article  Google Scholar 

  105. Wani, M. et al. Venous thromboembolism (VTE) in post-prostatectomy patients: systematic review and meta-analysis. J. Clin. Med. 12, 3979 (2023).

    Article  Google Scholar 

  106. Siech, C. et al. Cardiovascular disease and chronic pulmonary disease increase the risk of short-term major postoperative complications after robotic-assisted radical prostatectomy. Medicina 60, 173 (2024).

    Article  Google Scholar 

  107. Jones, C. U. et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N. Engl. J. Med. 365, 107–118 (2011).

    Article  CAS  Google Scholar 

  108. Nabid, A. et al. Duration of androgen deprivation therapy in high-risk prostate cancer: a randomized phase III trial. Eur. Urol. 74, 432–441 (2018).

    Article  CAS  Google Scholar 

  109. Bolla, M. et al. Concomitant and adjuvant androgen deprivation (ADT) with external beam irradiation (RT) for locally advanced prostate cancer: 6 months versus 3 years ADT — results of the randomized EORTC Phase III trial 22961. JCO 25, 5014–5014 (2007).

    Article  Google Scholar 

  110. Bolla, M. et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 11, 1066–1073 (2010).

    Article  CAS  Google Scholar 

  111. Zapatero, A. et al. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 16, 320–327 (2015).

    Article  CAS  Google Scholar 

  112. Gong, J. et al. Reduced cardiorespiratory fitness and increased cardiovascular mortality after prolonged androgen deprivation therapy for prostate cancer. JACC CardioOncol. 2, 553–563 (2020).

    Article  Google Scholar 

  113. Hufnagle, J. J., Andersen, S. N. & Maani, E. V. Radiation-induced cardiac toxicity StatPearls [Internet] https://www.ncbi.nlm.nih.gov/books/NBK554453/ (updated 29 May 2023).

  114. Guo, Y. et al. Effects of radiotherapy or radical prostatectomy on the risk of long-term heart-specific death in patients with prostate cancer. Front. Oncol. 10, 592746 (2020).

    Article  Google Scholar 

  115. Kjellstadli, C. et al. Cardiovascular outcomes after curative prostate cancer treatment: a population-based cohort study. Front. Oncol. 13, 1121872 (2023).

    Article  Google Scholar 

  116. Todaro, M. C. et al. Cardioncology: state of the heart. Int. J. Cardiol. 168, 680–687 (2013).

    Article  Google Scholar 

  117. Bendahou, H. et al. Cardiotoxicity due to docetaxel rare but it exists: about a case and literature review. J. Case Rep. Med. Hist. https://doi.org/10.54289/JCRMH2300105 (2023).

  118. Shimoyama, M., Murata, Y., Sumi, K.-I., Hamazoe, R. & Komuro, I. Docetaxel induced cardiotoxicity. Heart 86, 219–219 (2001).

    Article  CAS  Google Scholar 

  119. Rowinsky, E. K. et al. Cardiac disturbances during the administration of taxol. JCO 9, 1704–1712 (1991).

    Article  CAS  Google Scholar 

  120. Arbuck, S. G. et al. A reassessment of cardiac toxicity associated with taxol. J. Natl Cancer Inst. Monogr. 117, 130 (1993).

    Google Scholar 

  121. Page, R. L. et al. Drugs that may cause or exacerbate heart failure. Circulation 134, e32–e69 (2016).

    Article  CAS  Google Scholar 

  122. Rose, M., Burgess, J. T., O’Byrne, K., Richard, D. J. & Bolderson, E. PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance. Front. Cell Dev. Biol. 8, 564601 (2020).

    Article  Google Scholar 

  123. Inderjeeth, A.-J., Topp, M., Sanij, E., Castro, E. & Sandhu, S. Clinical application of poly(ADP-ribose) polymerase (PARP) inhibitors in prostate cancer. Cancers 14, 5922 (2022).

    Article  CAS  Google Scholar 

  124. Bhamidipati, D., Haro-Silerio, J. I., Yap, T. A. & Ngoi, N. PARP inhibitors: enhancing efficacy through rational combinations. Br. J. Cancer 129, 904–916 (2023).

    Article  CAS  Google Scholar 

  125. Friedlander, M., Lee, Y. C. & Tew, W. P. Managing adverse effects associated with poly (ADP-ribose) polymerase inhibitors in ovarian cancer: a synthesis of clinical trial and real-world data. Am. Soc. Clin. Oncol. Educ. Book 43, e390876 (2023).

    Article  Google Scholar 

  126. Palazzo, A. et al. Major adverse cardiac events and cardiovascular toxicity with PARP inhibitors-based therapy for solid tumors: a systematic review and safety meta-analysis. ESMO Open 8, 101154 (2023).

    Article  CAS  Google Scholar 

  127. Chen, W. et al. Hypertension associated with niraparib in cancer patients: a pharmacovigilance analysis based on the FAERS database and meta-analysis of randomized controlled trials. Gynecol. Oncol. 182, 108–114 (2024).

    Article  CAS  Google Scholar 

  128. Han, J.-Y., Seo, Y.-E., Kwon, J.-H., Kim, J. H. & Kim, M. G. Cardioprotective effects of PARP inhibitors: a re-analysis of a meta-analysis and a real-word data analysis using the FAERS database. J. Clin. Med. 13, 1218 (2024).

    Article  CAS  Google Scholar 

  129. Abida, W. et al. Non-BRCA DNA damage repair gene alterations and response to the PARP inhibitor rucaparib in metastatic castration-resistant prostate cancer: analysis from the phase II TRITON2 study. Clin. Cancer Res. 26, 2487–2496 (2020).

    Article  CAS  Google Scholar 

  130. Saad, F. et al. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 24, 1094–1108 (2023).

    Article  CAS  Google Scholar 

  131. Agarwal, N. et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet 402, 291–303 (2023).

    Article  CAS  Google Scholar 

  132. Chi, K. N. et al. Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer. JCO 41, 3339–3351 (2023).

    Article  CAS  Google Scholar 

  133. Tawagi, K., Schmolze, M., Nguyen, B., Laviana, A. & Reizine, N. PARP inhibitors in prostate cancer — understanding the current landscape. IJCCD https://doi.org/10.53876/001c.120988 (2024).

  134. Marshall, C. H. et al. Olaparib without androgen deprivation for high-risk biochemically recurrent prostate cancer following prostatectomy: a nonrandomized controlled trial. JAMA Oncol. 10, 1400–1408 (2024).

    Article  Google Scholar 

  135. Markowski, M. C. et al. TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline DNA repair gene mutations. JCO 41, 190–190 (2023).

    Article  Google Scholar 

  136. Vazquez, S. R. Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions. Blood 132, 2230–2239 (2018).

    Article  CAS  Google Scholar 

  137. LaFargue, C. J., Dal Molin, G. Z., Sood, A. K. & Coleman, R. L. Exploring and comparing adverse events between PARP inhibitors. Lancet Oncol. 20, e15–e28 (2019).

    Article  CAS  Google Scholar 

  138. Vinci, P. et al. Statin-associated myopathy: emphasis on mechanisms and targeted therapy. Int. J. Mol. Sci. 22, 11687 (2021).

    Article  CAS  Google Scholar 

  139. Beavers, C. J. et al. Cardio-oncology drug interactions: a scientific statement from the American Heart Association. Circulation 145, e811–e838 (2022).

    Article  Google Scholar 

  140. Bruin, M. A. C., Sonke, G. S., Beijnen, J. H. & Huitema, A. D. R. Pharmacokinetics and pharmacodynamics of PARP inhibitors in oncology. Clin. Pharmacokinet. 61, 1649–1675 (2022).

    Article  Google Scholar 

  141. Huynh-Le, M.-P., Shults, R. C., Connor, M. J. & Hattangadi-Gluth, J. A. Adverse events associated with radium-223 in metastatic prostate cancer: disproportionality analysis of FDA data reflecting worldwide utilization. Clin. Genitourin. Cancer 18, 192–200.e2 (2020).

    Article  Google Scholar 

  142. Hoskin, P. et al. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 15, 1397–1406 (2014).

    Article  CAS  Google Scholar 

  143. Jafari, E., Amini, A. L., Ahmadzadehfar, H., Bagheri, D. & Assadi, M. Cardiotoxicity and cardiac monitoring following the use of radiotheranostics agents including 177Lu-PSMA for prostate cancer and 177Lu-DOTATATE for neuroendocrine tumors. Nuklearmedizin 60, 99–105 (2021).

    Article  Google Scholar 

  144. Sartor, O. et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N. Engl. J. Med. 385, 1091–1103 (2021).

    Article  CAS  Google Scholar 

  145. Cheever, M. A. & Higano, C. S. PROVENGE (sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin. Cancer Res. 17, 3520–3526 (2011).

    Article  Google Scholar 

  146. Goff, D. C. et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk. Circulation 129, S49–S73 (2014).

    Article  Google Scholar 

  147. D’Agostino, R. B. Sr, Grundy, S., Sullivan, L. M. & Wilson, P. & for the CHD Risk Prediction Group. Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA 286, 180–187 (2001).

    Article  Google Scholar 

  148. Hippisley-Cox, J., Coupland, C. & Brindle, P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ 357, j2099 (2017).

    Article  Google Scholar 

  149. Khan, S. S. et al. Development and validation of the American Heart Association’s PREVENT equations. Circulation 149, 430–449 (2024).

    Article  Google Scholar 

  150. Bhatia, N. et al. Cardiovascular effects of androgen deprivation therapy for the treatment of prostate cancer. Circulation 133, 537–541 (2016).

    Article  Google Scholar 

  151. Klotz, L. et al. 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 (2008).

    Article  CAS  Google Scholar 

  152. Higano, C. S. et al. Risk of cardiovascular events with degarelix versus leuprolide after biochemical relapse of prostate cancer: exploratory analysis of a randomized controlled trial. JCO 33, 151–151 (2015).

    Article  Google Scholar 

  153. Zhu, J. et al. Toxicity profile characteristics of novel androgen-deprivation therapy agents in patients with prostate cancer: a meta-analysis. Expert. Rev. Anticancer. Ther. 18, 193–198 (2018).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Gatineau Hospital, McGill University, Gatineau, Quebec, Canada

    Steven Tisseverasinghe

  2. Department of Radiation Oncology, Dalhousie University, QEII Cancer Centre, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada

    Marwan Tolba

  3. Centre Hospitalier de l’Université de Montréal, Université de Montréal, Montreal, Quebec, Canada

    Fred Saad

  4. Department of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada

    Tamim Niazi

Authors
  1. Steven Tisseverasinghe
    View author publications

    Search author on:PubMed Google Scholar

  2. Marwan Tolba
    View author publications

    Search author on:PubMed Google Scholar

  3. Boris Bahoric
    View author publications

    Search author on:PubMed Google Scholar

  4. Fred Saad
    View author publications

    Search author on:PubMed Google Scholar

  5. Tamim Niazi
    View author publications

    Search author on:PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to Fred Saad or Tamim Niazi.

Ethics declarations

Competing interests

S.T. receives honoraria and consulting fees from Tolmar, AbbVie, Knight, Bayer, Janssen and Sumitomo pharma. M.T. receives honoraria and consulting fees from AbbVie, Tersera and Knight. F.S. has grants/contracts with Janssen, Bayer, Merck, Pfizer, Astellas, BMS, Novartis, Sanofi and AstraZeneca; receives consulting fees from Janssen, Bayer, Astellas, Novartis, Sanofi, AstraZeneca, Merck, Pfizer, Somitomo and Tolmar; and receives honoraria from Janssen, Bayer, Somitomo, Astellas, Novartis, Sanofi, AstraZeneca, Merck, Pfizer and Tolmar. T.N. has grants/contracts with Bayer, Jansen, Astellas, Tersera and Sanofi Canada; receives consulting fees from AbbVie, Astellas, Jansen, Tersera, Tolmar, Bayer, AAA, Pfizer, Knight, AstraZeneca and Sumitomo pharma; receives support for attending meetings/travel from Jansen, Tolmar, Knight and Bayer; and is the chair of the Quebec GU Radiation oncology group and co-chair of the Canadian GU radiation oncology group. B.B. declares no competing interests.

Peer review

Peer review information

Nature Reviews Urology thanks Joe O’Sullivan; Paul Sargos, who co-reviewed with Jennifer Le Guévelou; Tanya Dorff; and Ashwin Sachdeva, who co-reviewed with Omar El-Taji, for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tisseverasinghe, S., Tolba, M., Bahoric, B. et al. Assessing the effects of prostate cancer therapies on cardiovascular health. Nat Rev Urol 22, 509–525 (2025). https://doi.org/10.1038/s41585-025-01002-0

Download citation

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41585-025-01002-0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing