Androgen Deprivation Therapy, Hypogonadism and Cardiovascular Toxicity in Men with Advanced Prostate Cancer

Androgen deprivation therapy (ADT) is successfully used in patients with advanced prostatic cancer, but there are many concerns about its systemic side effects, especially due to advanced age and frequent comorbidities in most patients. In patients treated with ADT there are metabolic changes involving the glycaemic control and lipid metabolism, increased thrombotic risk, an increased risk of myocardial infarction, severe arrhythmia and sudden cardiac death. Still, these adverse effects can be also due to the subsequent hypogonadism. Men with heart failure or coronary artery disease have a lower level of serum testosterone than normal men of the same age, and hypogonadism is related to higher cardiovascular mortality. Many clinical studies compared the cardiovascular effects of hypogonadism post orchiectomy or radiotherapy with those of ADT but their results are controversial. However, current data suggest that more intensive treatment of cardiovascular risk factors and closer cardiological follow-up of older patients under ADT might be beneficial. Our paper is a narrative review of the literature data in this field.

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Cardiovascular and Metabolic Effects of Androgen-Deprivation Therapy for Prostate Cancer

Journal of Oncology Practice ◽

10.1200/jop.18.00178 ◽

2018 ◽

Vol 14 (10) ◽

pp. 580-587 ◽

Cited By ~ 15

Author(s):

Dipti Gupta ◽

Katherine Lee Chuy ◽

Ji Can Yang ◽

Megan Bates ◽

Marissa Lombardo ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Cardiovascular Events ◽

Advanced Prostate Cancer ◽

Serum Testosterone ◽

Management Plan ◽

Androgen Deprivation ◽

Metabolic Effects ◽

Increased Risk ◽

Hormone Sensitive

Androgen-deprivation therapy (ADT) entails lowering serum testosterone levels to castrate levels and forms a cornerstone of the management of hormone-sensitive advanced prostate cancer; however, the benefit of ADT is partially offset by its detrimental metabolic and cardiovascular adverse effects. ADT decreases insulin sensitivity while promoting dyslipidemia and sarcopenic obesity, which leads to an increased risk of cardiovascular morbidity and potentially mortality. The risk seems to be highest in elderly patients who have had recent cardiovascular events before starting ADT. It is prudent to engage in an individualized risk–benefit discussion and develop a cohesive multidisciplinary management plan to medically optimize and closely observe these patients before and during treatment with ADT.

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Prostate Carcinogenesis with Diabetes and Androgen-Deprivation-Therapy-Related Diabetes: An Update

Experimental Diabetes Research ◽

10.1155/2012/801610 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Noboru Hara

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Relevant Literature ◽

Serum Testosterone ◽

The United States ◽

Population Based ◽

Androgen Deprivation ◽

Prostate Carcinogenesis ◽

Increased Risk

Prostate cancer and the androgen deprivation therapy (ADT) thereof are involved in diabetes in terms of diabetes-associated carcinogenesis and ADT-related metabolic disorder, respectively. The aim of this study is to systematically review relevant literature. About 218,000 men are estimated to be newly diagnosed with prostate cancer every year in the United States. Approximately 10% of them are still found with metastasis, and in addition to them, about 30% of patients with nonmetastatic prostate cancer recently experience ADT. Population-based studies have shown that dissimilar to other malignancies, type 2 diabetes is associated with a lower incidence of prostate cancer, whereas recent large cohort studies have reported the association of diabetes with advanced high-grade prostate cancer. Although the reason for the lower prevalence of prostate cancer among diabetic men remains unknown, the lower serum testosterone and PSA levels in them can account for the increased risk of advanced disease at diagnosis. Meanwhile, insulin resistance already appears in 25–60% of the patients 3 months after the introduction of ADT, and long-term ADT leads to a higher incidence of diabetes (reported hazard ratio of 1.28–1.44). Although the possible relevance of cytokines such as Il-6 and TNF-αto ADT-related diabetes has been suggested, its mechanism is poorly understood.

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598: Increased Risk of Newly Diagnosed Comorbidities in Prostate Cancer Patients Treated with Androgen Deprivation Therapy

The Journal of Urology ◽

10.1016/s0022-5347(18)30838-3 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 200-200 ◽

Cited By ~ 1

Author(s):

Andrea Gallina ◽

Pierre I. Karakiewicz ◽

Jochen Walz ◽

Claudio Jeldres ◽

Quoc-Dien Trinh ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Newly Diagnosed ◽

Increased Risk

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Syncope due to non-sustained episodes of Torsade de Pointes associated to androgen-deprivation therapy use: a case presentation

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01945-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ximena Morales ◽

Diego Garnica ◽

Daniel Isaza ◽

Nicolas Isaza ◽

Felipe Durán-Torres

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Ejection Fraction ◽

Androgen Deprivation Therapy ◽

Torsade De Pointes ◽

Androgen Deprivation ◽

Atrial Pacing ◽

Case Presentation ◽

Reduced Ejection Fraction ◽

Artery Disease

Abstract Background Abiraterone is a medication frequently used for metastatic castrate-resistant prostate cancer. We report a case of non-sustained episodes of TdP associated with severe hypokalemia due to androgen-deprivation therapy. Few case presentations describe this association; the novelty lies in the potentially lethal cardiovascular events among cancer patients receiving hormonal therapy. Case presentation A 70-year-old male presented with recurrent syncope without prodrome. ECG revealed frequent ventricular ectopy, non-sustained episodes of TdP, and severe hypomagnesemia and hypokalemia. During potassium and magnesium infusion for repletion, the patient underwent temporary transvenous atrial pacing. As part of the work-up, coronary angiography revealed a mild coronary artery disease, and transthoracic echocardiogram showed a moderately depressed ejection fraction. After electrolyte disturbances were corrected, the QT interval normalized, and transvenous pacing was no longer necessary. Abiraterone was discontinued during the admission, and the patient returned to baseline. Conclusions Cancer treatment is complex and requires a multidisciplinary approach. We presented a case of non-sustained TdP associated with androgen-deprivation therapy in an elderly patient with mild coronary artery disease and moderately reduced ejection fraction. Close follow-up and increased awareness are required in patients with hormonal treatment, especially in the setting of other cardiovascular risk factors.

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Effect of androgen deprivation therapy on serum levels of sclerostin, Dickkopf-1, and osteoprotegerin: a cross-sectional and longitudinal analysis

Scientific Reports ◽

10.1038/s41598-021-94090-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alice Wang ◽

Nishi Karunasinghe ◽

Lindsay D. Plank ◽

Shuotun Zhu ◽

Sue Osborne ◽

...

Keyword(s):

Androgen Deprivation Therapy ◽

Longitudinal Analysis ◽

Serum Levels ◽

Androgen Deprivation ◽

Mineral Density ◽

Cross Sectional ◽

Prognostic Features ◽

Increased Risk ◽

Positive Correlations ◽

Dickkopf 1

AbstractAndrogen deprivation therapy (ADT) for men with prostate cancer (PCa) results in accelerated bone loss and increased risk of bone fracture. The aim of the present study was to evaluate serum bone markers—sclerostin, Dickkopf-1 (DKK-1) and osteoprotegerin (OPG), in a cohort of 88 PCa patients without known bone metastases, managed with and without ADT, and to analyse their relationship with bone mineral density (BMD) and sex steroids. The cross-sectional analysis between acute-, chronic- and former-ADT groups and PCa controls showed that sclerostin and OPG levels significantly differed between them (p = 0.029 and p = 0.032). Groups contributing to these significant changes were recorded. There were no significant differences in serum DKK-1 levels across the four groups (p = 0.683). In the longitudinal analysis, significant % decreases within groups were seen for DKK-1 [chronic-ADT (− 10.06%, p = 0.0057), former-ADT (− 12.77%, p = 0.0239), and in PCa controls group (− 16.73, p = 0.0022); and OPG levels in chronic ADT (− 8.28%, p = 0.003) and PCa controls group (− 12.82%, p = 0.017)]. However, % changes in sclerostin, DKK-1, and OPG did not differ significantly over 6-months across the evaluated groups. Sclerostin levels showed significant positive correlations with BMD at baseline in the ADT group, while in PCa controls this correlation existed at both baseline and 6-month time points. Sclerostin correlated negatively with testosterone in former ADT users and in PCa controls. Possible prognostic features denoted by parallel increases in sclerostin and BMD are discussed.

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No increased risk of psoriasis in patients receiving androgen deprivation therapy for prostate cancer: a 17-year population-based study

Therapeutics and Clinical Risk Management ◽

10.2147/tcrm.s175244 ◽

2018 ◽

Vol Volume 14 ◽

pp. 1831-1837 ◽

Cited By ~ 1

Author(s):

Jui-Ming Liu ◽

Chien-Yu Lin ◽

Heng-Chang Chuang ◽

Ren-Jun Hsu

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Population Based ◽

Androgen Deprivation ◽

Population Based Study ◽

Increased Risk

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The modern role of androgen deprivation therapy in the management of localised and locally advanced prostate cancer

Journal of Clinical Urology ◽

10.1177/2051415816654048 ◽

2016 ◽

Vol 9 (2_suppl) ◽

pp. 24-29 ◽

Cited By ~ 6

Author(s):

Charlotte Gunner ◽

Aziz Gulamhusein ◽

Derek J Rosario

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Advanced Prostate Cancer ◽

Locally Advanced ◽

Androgen Deprivation ◽

Locally Advanced Prostate Cancer ◽

Curative Intent ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk

Introduction: Approximately 50% of men diagnosed with prostate cancer will be exposed to androgen deprivation therapy (ADT) at some stage. The role of ADT in the management of metastatic disease has long been recognised, and its place in the management of localised and locally advanced disease has become clearer in the past few years. Nevertheless, concerns remain that some men might not benefit from ADT in earlier-stage disease. The purpose of the current article is to provide a brief narrative review of the role of ADT as part of a strategy of treatment with curative intent, concentrating mainly on key recent developments in the area. Methods: Narrative literature review of key publications in the English language relating to ADT in the management of localised and locally advanced prostate cancer. Results: In locally advanced and high-risk localised prostate cancer, the use of ADT in combination with radiotherapy improves disease-specific and overall survival. There is no evidence to support the use of ADT in the treatment of low-risk localised prostate cancer. There appears to be an increased risk of cardiovascular morbidity and mortality associated with luteinizing hormone-releasing hormone agonists, particularly in men with pre-existing cardiovascular disease, but the relevance of this in the adjuvant/neoadjuvant setting is currently unclear. Conclusions: Future studies should focus on identification of men who are at risk from cardiovascular complications associated with ADT and on the comparison of radiotherapy with ADT versus surgery in the management of localised and locally advanced prostate cancer, particularly with regards to men with pre-existing comorbidities.

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