Increased Risk of Metabolic Syndrome, Diabetes Mellitus, and Cardiovascular Disease in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

31 Background: Androgen deprivation therapy (ADT) has been associated with an increased risk of developing diabetes (DM) and cardiovascular disease (CVD), though this is controversial, particularly for CVD. We prospectively assessed the relationship between ADT and incident DM and CVD in the Prostate Cancer Outcomes Study (PCOS), a population-based cohort of prostate cancer survivors followed longitudinally for 15 years from diagnosis. Methods: We identified men in the PCOS with non-metastatic prostate cancer diagnosed from 1994 to 1995 and followed through 2009 to 2010. We used multivariable logistic regression models to compare groups receiving short-term ADT (less than 2 years), prolonged ADT (2 years or more) and no ADT to assess the relationship between ADT exposure and subsequent diagnoses of DM and CVD (determined by patient report and cause of death data). We evaluated the effects of age at diagnosis, race, stage, and comorbidity on the development of DM and CVD. Results: Among 3,526 men with comorbidity and treatment data, 2,985 men without baseline DM and 3,112 men without baseline CVD constituted the DM and CVD cohorts, respectively. Regardless of duration of ADT exposure, there was not an increased risk of DM or CVD in men younger than 70 at diagnosis. Compared to no ADT exposure, prolonged ADT was associated with an increased risk of DM and CVD that increased steadily over age 76 at diagnosis for DM (OR 2.11 at age 74, 95% CI 1.02 – 4.36; OR 2.65 at age 80, 95% CI 1.09 – 6.47) and age 74 at diagnosis for CVD (OR 1.89 at age 74, 95% CI 1.02 - 3.49; OR 3.19 at age 80, 95% 1.25 – 8.17). Increasing comorbidity burden modified risk of DM and CVD (for 3 or more comorbidities vs. no comorbidities; for DM, OR 4.25, 95% CI 2.3 - 7.9; and for CVD, OR 8.1, 95% CI 4.3 -15.5 P<0.001). Conclusions: The relationship between ADT and development of CVD and DM may be dependent upon age at diagnosis in addition to length of ADT administration, with longer ADT exposure predominantly increasing risk among older men only. Men with greater comorbid burden had increased risk of developing DM and CVD. Closer monitoring for development of DM and CVD may be most important among older men receiving prolonged ADT, especially those with other comorbidities.

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Metabolic syndrome in patients with prostate cancer undergoing intermittent androgen-deprivation therapy

Canadian Urological Association Journal ◽

10.5489/cuaj.3655 ◽

2016 ◽

Vol 10 (9-10) ◽

pp. 300 ◽

Cited By ~ 13

Author(s):

Mohammadali Mohammadzadeh Rezaei ◽

Mohammadhadi Mohammadzadeh Rezaei ◽

Alireza Ghoreifi ◽

Behzad Feyzzadeh Kerigh

Keyword(s):

Prostate Cancer ◽

Blood Pressure ◽

Metabolic Syndrome ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Safe Alternative ◽

Metabolic Complications ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Blood Pressures

Introduction: The presence of metabolic syndrome in men with prostate cancer (PCa) undergoing androgen-deprivation therapy (ADT), especially intermittent type, has not been completely evaluated. The aim of this study is to evaluate metabolic syndrome in men with PCa undergoing intermittent ADT.Methods: In this longitudinal study, we studied the prevalence of metabolic syndrome and its components in 190 patients who were undergoing intermittent ADT. The metabolic syndrome was defined according to the Adult Treatment Panel III criteria. All metabolic parameters, including lipid profile, blood glucose, blood pressures, and waist circumferences of the patients were measured six and 12 months after treatment.Results: Mean age of the patients was 67.5 ± 6.74 years. The incidence of metabolic syndrome after six and 12 months was 6.8% and 14.7%, respectively. Analysis of various components of the metabolic syndrome revealed that patients had significantly higher overall prevalence of hyperglycemia, abdominal obesity, and hypertriglyceridemia in their six- and 12-month followups, but blood pressure has not been changed in the same period except for diastolic blood pressure after six months.Conclusions: Although there was an increased risk of metabolic syndrome in patients receiving intermittent ADT, it was lower than other studies that treated the same patients with continuous ADT. Also it seems that intermittent ADT has less metabolic complications than continuous ADT and could be used as a safe alternative in patients with advanced and metastatic PCa.

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The Association between the Risk of Cardiovascular Disease and Androgen Deprivation Therapy in Patients with Prostate Cancer. A Meta-Analysis and systematic review.

10.21203/rs.2.10884/v3 ◽

2019 ◽

Author(s):

Zhen Liang ◽

Jun Zhu ◽

Xiaoxin Duo ◽

Shangheng Shi ◽

Yawei Xu ◽

...

Keyword(s):

Prostate Cancer ◽

Heart Failure ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Meta Analysis ◽

Androgen Deprivation ◽

Relative Risk Ratio ◽

Control Group ◽

Gnrh Agonists ◽

Increased Risk

Abstract Background : Androgen deprivation therapy (ADT) is widely being applied in men who suffered from prostate cancer, our aim is to evaluate whether ADT is associated with an excess risk of cardiovascular disease (CVD). Method : Studies comparing the the incidence of CVD between ADT group and control group were identified through literature search in electronic databases (Pubmed, Embase, Web of Science) until July 2019 and only observational studies and randomized controlled trials (RCT) were included. The estimating relative risk ratio (RR) and 95% confidence intervals (CI) were calculated through random effects meta-analyses. Result : A statistically significant association was detected for acute myocardial infarction (AMI) with RR = 1.22; 95% confidence interval CI, 1.05–1.43; P< 0.05. Significant relationship between coronary heart disease (CHD) and ADT was also observed, with summary RR=1.19; 95%CI, 1.03-1.38; P<0.05. ADT was associated with a risk increasement for heart failure (HF) with RR=1.15; 95% CI 1.01–1.33; P< 0.05. On the contrary, ADT was not associated with an increased risk of sudden cardiac death (SCD). Conclusions : From this study, ADT is associated with increased risk of AMI, CHD, and heart failure (HF); in contrast, this association is not detected in SCD; various modalities of ADT could significantly increase the risk of CHD, AMI, except for oral anti-androgen (AA). Our meta-analysis also suggests that the long-term application of ADT in prostate cancer patients would not result in a significant increase in AMI incidence compared with short-term. Moreover, the combined application of AA and GnRH agonists would lead to a similar risk of AMI compared with orchiectomy or GnRH agonists monotherapy whereas higher risk of CHD was detected when compared GnRH agonists plus AA with orchiectomy.

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Prevalence of Diabetes Mellitus and Metabolic Syndrome in Prostate Cancer Patients Given Androgen Deprivation Therapy

10.1210/endo-meetings.2011.part2.p10.p1-512 ◽

2011 ◽

pp. P1-512-P1-512

Author(s):

Maria Luisa Cecilia Rivera Arkoncel ◽

Michael Sagun ◽

Francis Raymond Arkoncel ◽

Cecilia Jimeno ◽

Marie Carmela Lapitan

Keyword(s):

Prostate Cancer ◽

Diabetes Mellitus ◽

Metabolic Syndrome ◽

Cancer Patients ◽

Androgen Deprivation Therapy ◽

Androgen Deprivation ◽

Prevalence Of Diabetes Mellitus

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Association of metabolic syndrome with reduced survival among men receiving androgen deprivation therapy for nonmetastatic prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.56 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 56-56 ◽

Cited By ~ 4

Author(s):

Sarah Maria Rudman ◽

Kathryn P. Gray ◽

Julie Kasperzyk ◽

Michael Pitt ◽

Edward Giovannucci ◽

...

Keyword(s):

Prostate Cancer ◽

Metabolic Syndrome ◽

Androgen Deprivation Therapy ◽

Cumulative Incidence ◽

Androgen Deprivation ◽

Risk Of Death ◽

The Metabolic Syndrome ◽

Obesity And Diabetes ◽

Increased Risk

56 Background: The metabolic syndrome (MS) is a set of risk factors implicated in both the development of prostate cancer (PC) and as a recognized complication of androgen deprivation therapy (ADT). In our previous study of a Veterans’ Administration (VA) cohort of relapsed PC patients (pts) on ADT, MS was associated with a shorter duration of PC control. Methods: We studied 347 patients (72 from VA and 275 from Health Professionals Follow up Study) treated with ADT for non-metastatic PC. 88% for biochemical relapse post definitive local therapy and 12% treated with primary ADT. MS was assessed by the modified Adult Treatment Panel III criteria prior to the commencement of ADT. Cox models tested for association between MS status and time to overall survival (OS) or time to PC specific survival, stratified by cohorts (VA vs. HPFS). Cumulative incidence of PC specific death (accounting for competing risk of death from other causes and co-morbidities) by MS status was estimated. Results: 96 patients (28%) had MS. 62 patients (18%) died of PC during a median follow-up of 9.5 years. The median OS for patients with and without MS was 7.5 and 10.6 years respectively. A multivariate Cox model adjusted for age at start of ADT, diagnosis, stage, Gleason score and primary treatment showed MS was associated with a significant 53% increased risk of death from any cause (HR(95%CI) 1.53(1.05-2.22); p=0.03). MS patients tended to have increased risk of PC specific death (HR(95%CI) 1.6 (0.9-2.84); p=0.11). Individual MS components hypertension, dyslipidemia, obesity and diabetes were not associated with an increased risk of death from any cause or PC. The cumulative incidence of PC specific death did not differ by MS status. Conclusions In men receiving ADT for androgen dependent PC without metastases, the presence of MS at the commencement of ADT is associated with an increased risk of death compared to those pts without MS. The shorter time to death appears to be at least in part due to shorter time to dying from PC.

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Is Androgen Deprivation Therapy for Prostate Cancer Associated with Cardiovascular disease ? A Meta-Analysis and systematic review.

10.21203/rs.2.10884/v1 ◽

2019 ◽

Author(s):

Zhen Liang ◽

Longlong Chen ◽

Yawei Xu ◽

Yongjiao Yang ◽

Rui Hu ◽

...

Keyword(s):

Prostate Cancer ◽

Systematic Review ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Disease Risk ◽

Meta Analysis ◽

Androgen Deprivation ◽

Increased Risk ◽

Significant Difference ◽

The Relationship

Abstract Background: Whether androgen deprivation therapy (ADT) is associated with an increased risk of developing cardiovascular related disease is poorly defined. The aim of the present meta‐analysis is to explore the relationship between ADT and the risk of cardiovascular disease (CVD). Method: For this systematic review and meta-analysis, we searched databases until April 2019 for randomized controlled trial (RCT) or observational studies that reported data on ADT administration and cardiovascular disease (CVD) incidence. The relationship was evaluated through estimate relative risk ratio (RR) and 95% confidence intervals (CIs) Result: A statistically significant difference was detected for acute myocardial infarction (AMI) (RR = 1.13; 95% CI, 1.10–1.15; P< 0.05) including a total of 142,186 cases and 174,404 controls. Significant difference between coronary heart disease (CHD) and ADT was also observed, with summary (RR=1.11; 95% confidence interval CI: 1.10-1.13), from 157,339 ADT users and 349,636 non-ADT users of 7 eligible studies. Conclusions: Pooled result demonstrated that ADT could significantly increase the risk of CHD, AMI and sudden cardiac death (SCD). Various ADT modalities have different impact on cardiovascular disease risk in different level. Our meta-analysis also suggests that the application of ADT in prostate cancer patients for over 5 years resulted in a significant increase in cardiovascular morbidity. Moreover, subgroup analyses for different types of ADT indicated that compared with the individual administration of ADT, GnRH plus AA (oral anti-androgens) is more likely significantly lead to AMI.

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The Association between the Risk of Cardiovascular Disease and Androgen Deprivation Therapy in Patients with Prostate Cancer. A Meta-Analysis and systematic review.

10.21203/rs.2.10884/v2 ◽

2019 ◽

Author(s):

Zhen Liang ◽

Jun Zhu ◽

Xiaoxin Duo ◽

Shangheng Shi ◽

Yawei Xu ◽

...

Keyword(s):

Prostate Cancer ◽

Cardiovascular Disease ◽

Androgen Deprivation Therapy ◽

Meta Analysis ◽

Androgen Deprivation ◽

Relative Risk Ratio ◽

Gnrh Agonists ◽

Combined Application ◽

Increased Risk

Abstract Background : Androgen deprivation therapy (ADT) is widely being applied in men who suffered from prostate cancer, our aim is to evaluate whether ADT is associated with an excess risk of cardiovascular disease (CVD). Method : Literature search in electronic databases was conducted until July 2019 for observational studies and randomized controlled trials (RCT) to select eligible studies. The relationship was evaluated through estimating relative risk ratio (RR) and 95% confidence intervals (CI). Result : A statistically significant association was detected for acute myocardial infarction (AMI) with RR = 1.22; 95% confidence interval CI, 1.05–1.43; P< 0.05 including a total of 142,012 cases and 174,099 controls. Significant relationship between coronary heart disease (CHD) and ADT was also observed, with summary RR=1.19; 95%CI, 1.03-1.38, from 157,165 ADT users and 375,754 non-ADT users. Conclusions : From this study, ADT is associated with increased risk of AMI, CHD, and heart failure (HF); in contrast, this association is not detected in sudden cardiac death (SCD); various modalities of ADT could significantly increase the risk of CHD, AMI, except for oral anti-androgen (AA). Our meta-analysis also suggests that the long-term application of ADT in prostate cancer patients would not result in a significant increase in AMI incidence compared with short-term. Moreover, the combined application of AA and GnRH agonists would lead to a similar risk of AMI compared with orchiectomy or GnRH agonists monotherapy whereas higher risk of CHD was detected when compared GnRH agonists plus AA with orchiectomy.

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