Androgen deprivation therapy may be linked to increased risk of dementia

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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Influence of age on incident diabetes (DM) and cardiovascular disease (CVD) among prostate cancer survivors receiving androgen deprivation therapy (ADT).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.31 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 31-31

Author(s):

Alicia Katherine Morgans ◽

Kang-Hsien Fan ◽

Tatsuki Koyama ◽

Peter C. Albertsen ◽

Michael Goodman ◽

...

Keyword(s):

Prostate Cancer ◽

Cardiovascular Disease ◽

Cancer Survivors ◽

Androgen Deprivation Therapy ◽

Older Men ◽

Androgen Deprivation ◽

Age At Diagnosis ◽

Prostate Cancer Survivors ◽

Increased Risk ◽

The Relationship

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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Proportion of biochemically-recurrent prostate cancer patients with durable undetectable PSA after short-course androgen deprivation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.207 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 207-207

Author(s):

Daniel M. Lim ◽

Roman Gulati ◽

Serge Aleshin-Guendel ◽

Heather H. Cheng ◽

Agnes M. Gawne ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Specific Antigen ◽

Initial Therapy ◽

Androgen Deprivation ◽

Clinical Value ◽

Short Course ◽

Increased Risk ◽

The University ◽

Trial Endpoint

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.

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Androgen-Deprivation Therapy for Nonmetastatic Prostate Cancer Is Associated With an Increased Risk of Peripheral Arterial Disease and Venous Thromboembolism

European Urology ◽

10.1016/j.eururo.2012.01.045 ◽

2012 ◽

Vol 61 (6) ◽

pp. 1119-1128 ◽

Cited By ~ 63

Author(s):

Jim C. Hu ◽

Stephen B. Williams ◽

A. James O'Malley ◽

Matthew R. Smith ◽

Paul L. Nguyen ◽

...

Keyword(s):

Prostate Cancer ◽

Venous Thromboembolism ◽

Peripheral Arterial Disease ◽

Androgen Deprivation Therapy ◽

Arterial Disease ◽

Androgen Deprivation ◽

Increased Risk ◽

Peripheral Arterial

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Androgen Deprivation Therapy and Cardiovascular Risk

Journal of Clinical Oncology ◽

10.1200/jco.2011.35.1494 ◽

2011 ◽

Vol 29 (26) ◽

pp. 3510-3516 ◽

Cited By ~ 52

Author(s):

Sanoj Punnen ◽

Matthew R. Cooperberg ◽

Natalia Sadetsky ◽

Peter R. Carroll

Keyword(s):

Cardiovascular Risk ◽

Propensity Score ◽

Androgen Deprivation Therapy ◽

Local Treatment ◽

Local Therapy ◽

National Registry ◽

Androgen Deprivation ◽

Treatment Selection ◽

Increased Risk ◽

Significant Difference

Purpose The potential association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM) remains controversial. This study assessed mortality outcomes in a large national registry to further elucidate the association between treatment selection and cause of mortality. Patients and Methods A total of 7,248 men in the CaPSURE registry were analyzed. Treatment was categorized as local only, primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS). Competing hazards survival analysis was performed for prostate cancer–specific mortality (PCSM), CVM, and all-cause mortality. A propensity score–adjusted and a propensity-matched analysis were undertaken to adjust for imbalances in covariates among men receiving various treatments. Results Patients treated with ADT or WW/AS had a higher likelihood of PCSM than those treated with local therapy alone. Patients treated with primary ADT had an almost two-fold greater likelihood of CVM (HR, 1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however, patients treated with WW/AS had a greater than two-fold increased risk of CVM (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of 1,391 patients was unable to find a significant difference in CVM between those who did or did not receive ADT. Conclusion Patients matched on propensity to receive ADT did not show an association between ADT and CVM. This suggests that potential unmeasured variables affecting treatment selection may confound the relationship between ADT use and cardiovascular risk. However, an association may yet exist, because the propensity score could not include all known risk factors for CVM.

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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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