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

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.

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

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.

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

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.

scholarly journals Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer

2015 ◽  
Vol 33 (11) ◽  
pp. 1243-1251 ◽  
Author(s):  
Sean O'Farrell ◽  
Hans Garmo ◽  
Lars Holmberg ◽  
Jan Adolfsson ◽  
Pär Stattin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cardiovascular Disease ◽  
Androgen Deprivation Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Gnrh Agonists ◽  
Cvd Risk ◽  
Comparison Cohort ◽  
Using Data

Purpose Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent. Methods By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models. Results From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort. Conclusion Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

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

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.

scholarly journals Influence of androgen deprivation therapy on glucose metabolism and ambulatory glucose profile

2021 ◽  
pp. 172-182
Author(s):  
E. Yu. Grickevich ◽  
D. V. Skuridina ◽  
S. N. Perekhodov
Keyword(s):  
Prostate Cancer ◽  
Glucose Metabolism ◽  
Androgen Deprivation Therapy ◽  
Locally Advanced ◽  
Androgen Deprivation ◽  
Glucose Metabolism Disorders ◽  
Gnrh Agonists ◽  
Glucose Profile ◽  
Freestyle Libre

Introduction. Androgen deprivation, used to treat prostate cancer, leads to metabolic disorders, including glucose metabolism disorders. The timing of development and the characteristics of these changes have not been sufficiently studied. The expansion of the possibilities for assessing glycemia makes it possible to obtain changes in glucose.Objective. To study the dynamics of the effect of long-term androgen-deprivation therapy with gonadotropin-releasing hormone agonists (GnRH agonists) on the parameters of glucose metabolism and ambulatory glucose profile in patients with locally advanced prostate cancer (La PCa).Materials and methods. The study included 99 patients with La PCa receiving androgendeprivation therapy (ADT) with (GnRH agonists) for at least 12 months. The study of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) levels was performed at baseline, after 3, 6 and 12 months of ADT, and constant self-monitoring of glycemia was recommended using portable glucometers. Flash glucose monitoring systems (FreeStyle Libre) were installed in ten patients with a detected increase in glycemia on the background of ADT, allowing them to obtain data on the ambulatory glucose profile (AGP).Results and discussion. Long-term ADT in patients with La PCa, regardless of baseline age, BMI, WC, was accompanied by an early, progressive deterioration in parameters of glucose metabolism. The proportion of patients with prediabetic FPG values after 12 months becames 66% according ADA criteria. We found that 12-month ADT changes the AGP: an increase area under the curve and postprandial glycemic levels, an increase in blood glucose variability with an increase in the CONGA index to 6.817 (p < 0.001).Conclusion. ADT by GnRH agonists in patients with La PCa is accompanied by a predisposition to early disorders of glucose metabolism with a high risk of rapid development of prediabetes regardless of baseline age, BMI, and WC. The AGP of patients is characterized by an increase in the total glycemic load, and glycemic variability.

scholarly journals Retrospective cohort study of androgen deprivation therapy and the risk of diabetes in men with prostate cancer in Lithuania

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e045797
Author(s):  
Mingaile Drevinskaite ◽  
Ausvydas Patasius ◽  
Marius Kincius ◽  
Vincas Urbonas ◽  
Giedre Smailyte
Keyword(s):  
Prostate Cancer ◽  
Type 2 Diabetes ◽  
Cohort Study ◽  
Androgen Deprivation Therapy ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Androgen Deprivation ◽  
Gnrh Agonists ◽  
Increased Risk

ObjectivesTo examine the risk of type 2 diabetes in patients with prostate cancer and its association with androgen deprivation therapy (ADT).Design and participantsWe performed a retrospective cohort study of patients diagnosed with prostate cancer in the Lithuanian male population between 1 January 2003 and 31 December 2012 who were identified through the Lithuanian Cancer registry. All prostate cancer cases were linked to the National Health Insurance Fund database to obtain information regarding the diagnosis of diabetes mellitus and information on prescriptions of antiandrogens and gonadotropin-releasing hormone (GnRH) agonists. Patients with prostate cancer were followed up until the diagnosis of type 2 diabetes, or 31 December 2017, or date of death, whichever came first. Cox proportional hazard models were used to estimate the risk of type 2 diabetes in patients with prostate cancer with or without ADT exposure.Results27 580 men were diagnosed with prostate cancer, out of whom 14 502 (52.6%) did not receive ADT and 13 078 (47.4%) were treated with ADT. The incidence of type 2 diabetes for all patients with prostate cancer was 7.4/1000 person-years, for men on GnRH agonists 9.0/1000 person-years and 5.8/1000 person-years for men on antiandrogens. There was an increased risk of developing type 2 diabetes comparing ADT users and non-users (HR=1.49, 95% CI 1.34 to 1.66).ConclusionThis study showed an increased risk of diabetes in patients with prostate cancer treated with ADT in comparison to ADT-free patient cohort. GnRH agonist users showed higher susceptibility, while the group on antiandrogen monotherapy showed no such increase.

scholarly journals SAT0468 EFFECTS OF ANDROGEN DEPRIVATION THERAPY ON BONE QUALITY (TBS) IN PATIENTS WITH PROSTATE CANCER

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1191.2-1192
Author(s):  
S. Garcia-Cirera ◽  
E. Casado ◽  
J. Muñoz ◽  
L. Del Río ◽  
M. Arévalo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lumbar Spine ◽  
Androgen Deprivation Therapy ◽  
Bone Quality ◽  
Bone Microarchitecture ◽  
Androgen Deprivation ◽  
Mineral Density ◽  
Increased Risk ◽  
One Year

Background:Androgen deprivation therapy (ADT), by inducing severe hypogonadism, leads to a loss of bone mineral density (BMD) and an increased risk of fragility fractures after 6 months of treatment in men with prostate cancer1. However, its effect on bone quality has not been described.Objectives:To evaluate the changes on bone microarchitecture (bone quality) assessed by TBS (trabecular Bone Score) in male patients with prostate cancer after one year of treatment with ADT.Methods:All patients diagnosed with prostate cancer candidates for long-term ADT admitted to Urology department of Hospital Universitari Parc Tauli (reference population of 450,000 inhabitants) between April 2017 and December 2019 were included. Patients who received chemotherapy, previous hormonal therapy or specific treatment for osteoporosis in the last year or those who had a very impaired functional capacity (Barthel index <30) were excluded.Demographic, clinical and analytical data (testosterone, calcium, phosphorous, alkaline phosphatase, 25-hidroxyvitamin D, PTH) were collected in all patients. A bone densitometry (GE-Lunar Prodigy) including the measurement of lumbar spine TBS (L1-L4) using Medimaps Software was performed at baseline and at 12 months of treatment with ADT.Results:78 patients were included. Mean age 77,9±8,3 years. The median Gleason score was 7,88±1,05. 3 patients had previous fragility fracture (one sacral fracture, one fibula and one multiple vertebral fracture). Baseline analytical values in patients were the following: testosterone11,6±74,9 nmol/L.; 25-hidroxyvitamin D 20,8±10,4 ng/ml; PTH 51,8±23,0 pg/ml; CTX 0,58±0,66. The daily calcium intake was 573±207 mg/day.According to BMD, 17 patients (21,8%) had osteoporosis before starting ADT, with the following average T-score values: lumbar spine +0,15±1,85, femoral neck -1,75±1,00, and total hip -1,19±1,16. Mean baseline TBS value of the entire cohort was 1,279±0,122. 30,5% of the patients showed very degraded microarchitecture (TBS<1,230), 28,8% had partially degraded microarchitecture (TBS 1,230-1,310) and in 40,7% showed normal microarchitecture (TBS >1,310).After one year of ADT treatment, TBS mildly worsened in this cohort, with a median value of 1,256±0,131 (p = NS). However up to 43% of patients reached highly degraded microarchitecture, 27% partially degraded and only 29,5% had a normal TBS (p = NS).Conclusion:Most patients with prostate cancer have an altered bone quality before starting ADT. After 12 months of treatment, the percentage of patients with highly degraded bone microarchitecture increases, although not significantly. More studies are needed to confirm this trend and to evaluate if these patients present more long-term fractures.References:[1]Lee R, et al. Bone 2011; 48 (1): 88-95Disclosure of Interests:Silvia Garcia-Cirera: None declared, Enrique Casado Speakers bureau: UCB, Lilly, Amgen, Theramex, Gebro, Gedeon-Richter, Stada, Jesús Muñoz: None declared, Luis Del Río: None declared, Marta Arévalo: None declared, Menna Rusiñol: None declared, Noemí Navarro: None declared, Víctor Parejo: None declared, Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly

Androgen deprivation therapy in the treatment of prostate cancer and dementia risk: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5044-5044
Author(s):  
Kevin Thomas Nead ◽  
Sumi Sinha ◽  
Paul L. Nguyen
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Androgen Deprivation Therapy ◽  
Meta Analysis ◽  
Androgen Deprivation ◽  
Small Study ◽  
Effect Estimate ◽  
Neurocognitive Deficits ◽  
Dementia Risk ◽  
Increased Risk

5044 Background: Androgen deprivation therapy (ADT) to treat prostate cancer may be associated with an increased risk of dementia, but existing studies have shown conflicting results. Here we conduct a systematic review and meta-analysis on the association of ADT in the treatment of prostate cancer with the risk of dementia. Methods: We conducted a systematic review of articles reporting the outcome of dementia among individuals with prostate cancer in those exposed to ADT versus a lesser-exposed comparison group (e.g. no ADT, intermittent ADT) using the PRISMA statement guidelines. Two authors independently carried out searches in PubMed (1966–present), Web of Science (1945–present), Embase (1966–present), and PsycINFO (1806–present). The search was undertaken December 4th, 2016. We assessed the validity of each study per the Newcastle-Ottawa Scale criteria. We meta-analyzed studies reporting an effect estimate and controlling for confounding.Random- or fixed-effects meta-analytic models were used in the presence or absence of heterogeneity, respectively, per the I2statistic. Small study effects were evaluated using Egger and Begg’s tests. Results: Nine studies were included in the systematic review. Seven studies reported an adjusted effect estimate for dementia risk. A random-effects meta-analysis of studies reporting any dementia outcome, which included 50,541 individuals, showed an increased risk of dementia among ADT users (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08–2.00; p = 0.02). We separately meta-analyzed studies reporting all-cause dementia (HR, 1.46; 95% CI, 1.05–2.02; p < 0.001) and Alzheimer’s disease (HR, 1.25; 95% CI, 0.99–1.57; p = 0.06). The I2statistic to evaluate the proportion of heterogeneity due to study variation was 76% (95% CI, 47–89; p < 0.001) for the primary analysis. There was no evidence of bias from small study effects (Egger, p = 0.19; Begg, p = 1.00). Conclusions: The currently available combined evidence suggests that ADT in the treatment of prostate cancer may be associated with an increased risk of dementia. The potential for neurocognitive deficits secondary to ADT should be discussed with patients and evaluated prospectively.

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