scholarly journals Impact of Androgen Deprivation Therapy on Cardiovascular Disease and Diabetes

2009 ◽  
Vol 27 (21) ◽  
pp. 3452-3458 ◽  
Author(s):  
Shabbir M.H. Alibhai ◽  
Minh Duong-Hua ◽  
Rinku Sutradhar ◽  
Neil E. Fleshner ◽  
Padraig Warde ◽  
...  

Purpose Use of androgen deprivation therapy (ADT) may be associated with an increased risk of diabetes mellitus but the risk of both acute myocardial infarction (AMI) and cardiovascular mortality remain controversial because few outcomes and conflicting findings have been reported. We sought to clarify whether ADT is associated with these outcomes in a large, representative cohort. Methods Using linked administrative databases in Ontario, Canada, men age 66 years or older with prostate cancer given continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 19,079) were matched with men with prostate cancer who had never received ADT. Treated and untreated groups were matched 1:1 (ie, hard-matched) on age, prior cancer treatment, and year of diagnosis and propensity-matched on comorbidities, medications, cardiovascular risk factors, prior fractures, and socioeconomic variables. Primary outcomes were development of AMI, sudden cardiac death, and diabetes. Fragility fracture was also examined. Results The cohort was observed for a mean of 6.47 years. In time-to-event analyses, ADT use was associated with an increased risk of diabetes (hazard ratio [HR], 1.16; 95% CI, 1.11 to 1.21) and fragility fracture (HR, 1.65; 95% CI, 1.53 to 1.77) but not with AMI (HR, 0.91; 95% CI, 0.84 to 1.00) or sudden cardiac death (HR, 0.96; 95% CI, 0.83 to 1.10). Increasing duration of ADT was associated with an excess risk of fragility fractures and diabetes but not cardiac outcomes. Conclusion Continuous ADT use for at least 6 months in older men is associated with an increased risk of diabetes and fragility fracture but not AMI or sudden cardiac death.

2006 ◽  
Vol 24 (27) ◽  
pp. 4448-4456 ◽  
Author(s):  
Nancy L. Keating ◽  
A. James O'Malley ◽  
Matthew R. Smith

Purpose Androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist is associated with increased fat mass and insulin resistance in men with prostate cancer, but the risk of obesity-related disease during treatment has not been well studied. We assessed whether androgen deprivation therapy is associated with an increased incidence of diabetes and cardiovascular disease. Patients and Methods Observational study of a population-based cohort of 73,196 fee-for-service Medicare enrollees age 66 years or older who were diagnosed with locoregional prostate cancer during 1992 to 1999 and observed through 2001. We used Cox proportional hazards models to assess whether treatment with GnRH agonists or orchiectomy was associated with diabetes, coronary heart disease, myocardial infarction, and sudden cardiac death. Results More than one third of men received a GnRH agonist during follow-up. GnRH agonist use was associated with increased risk of incident diabetes (adjusted hazard ratio [HR], 1.44; P < .001), coronary heart disease (adjusted HR, 1.16; P < .001), myocardial infarction (adjusted HR, 1.11; P = .03), and sudden cardiac death (adjusted HR, 1.16; P = .004). Men treated with orchiectomy were more likely to develop diabetes (adjusted HR, 1.34; P < .001) but not coronary heart disease, myocardial infarction, or sudden cardiac death (all P > .20). Conclusion GnRH agonist treatment for men with locoregional prostate cancer may be associated with an increased risk of incident diabetes and cardiovascular disease. The benefits of GnRH agonist treatment should be weighed against these potential risks. Additional research is needed to identify populations of men at highest risk of treatment-related complications and to develop strategies to prevent treatment-related diabetes and cardiovascular disease.


2007 ◽  
Vol 177 (4S) ◽  
pp. 200-200 ◽  
Author(s):  
Andrea Gallina ◽  
Pierre I. Karakiewicz ◽  
Jochen Walz ◽  
Claudio Jeldres ◽  
Quoc-Dien Trinh ◽  
...  

2016 ◽  
Vol 9 (2_suppl) ◽  
pp. 24-29 ◽  
Author(s):  
Charlotte Gunner ◽  
Aziz Gulamhusein ◽  
Derek J Rosario

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.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 31-31
Author(s):  
Alicia Katherine Morgans ◽  
Kang-Hsien Fan ◽  
Tatsuki Koyama ◽  
Peter C. Albertsen ◽  
Michael Goodman ◽  
...  

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.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 207-207
Author(s):  
Daniel M. Lim ◽  
Roman Gulati ◽  
Serge Aleshin-Guendel ◽  
Heather H. Cheng ◽  
Agnes M. Gawne ◽  
...  

207 Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate specific antigen (PSA) levels as a marker of efficacy. The proportion of patients and clinical relevance of those with a prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6–12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥ 0.2 ng/mL and no radiographically detectable metastasis. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death from any cause were evaluated by log-rank tests. Results: After ineligibility exclusions, data were abstracted from 93 patients. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were n=23/93 (24.7%; 95% CI 16.4–34.8%; P<0.001) and n=14/93 (15.1%; 95% CI 8.5–24.0%; P<0.001), respectively. Proportions of patients with undetectable PSA 12 and 24 months after testosterone recovery ≥ 50 ng/dL were n=16/65 (24.6%; 95% CI 14.8-36.9%) and n=10/65 (15.4%; 95% CI 7.6-26.5%), respectively. Being 1 year older at diagnosis was associated with an 11.5% (95% CI 3.1–21.9%; P=0.01) increase in the odds of having a detectable PSA after controlling for PSA at diagnosis, Gleason sum and time from initial therapy to BCR. Detectable PSA was associated with increased risk of metastasis (P=0.006) with marginal evidence of association with death from any cause (P=0.07). Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. Additional analysis is needed to demonstrate the clinical value of this measure as a surrogate for prostate cancer outcomes and for consideration as a trial endpoint.


2016 ◽  
Vol 10 (9-10) ◽  
pp. 300 ◽  
Author(s):  
Mohammadali Mohammadzadeh Rezaei ◽  
Mohammadhadi Mohammadzadeh Rezaei ◽  
Alireza Ghoreifi ◽  
Behzad Feyzzadeh Kerigh

<p><strong>Introduction:</strong> 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.</p><p><strong>Methods:</strong> 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.</p><p><strong>Results:</strong> 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.</p><p><strong>Conclusions:</strong> 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.</p>


2019 ◽  
Author(s):  
Zhen Liang ◽  
Jun Zhu ◽  
Xiaoxin Duo ◽  
Shangheng Shi ◽  
Yawei Xu ◽  
...  

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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