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

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Noboru Hara

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.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1191.2-1192
Author(s):  
S. Garcia-Cirera ◽  
E. Casado ◽  
J. Muñoz ◽  
L. Del Río ◽  
M. Arévalo ◽  
...  

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


2018 ◽  
Vol 14 (10) ◽  
pp. 580-587 ◽  
Author(s):  
Dipti Gupta ◽  
Katherine Lee Chuy ◽  
Ji Can Yang ◽  
Megan Bates ◽  
Marissa Lombardo ◽  
...  

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.



2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 163-163
Author(s):  
Jennifer Beebe-Dimmer ◽  
Karynsa Cetin ◽  
Cecilia Yee ◽  
Scott Stryker ◽  
Lois Lamerato ◽  
...  

163 Background: Androgen deprivation therapy (ADT) is the cornerstone treatment of metastatic prostate cancer (PC), but is frequently used in the non-metastatic (M0) setting. After a variable period of hormone sensitivity, most patients develop castration-resistant prostate cancer (CRPC). These men are at increased risk of developing bone metastases (BM), particularly in those with higher serum PSA and shorter PSA doubling time (DT). The epidemiology and natural history of M0 CRPC has not been well studied in a population-based setting. Methods: Using HFHS patient records, a retrospective cohort study was conducted among 723 men diagnosed with M0 PC between 1996 and 2005 (with follow-up [f/u] for outcomes through 12/31/2008), who received ADT, including 613 men with serial PSA measurements for CRPC determination. CRPC was defined as 2 consecutive PSA rises, with “high-risk” defined as PSA ≥ 8 ng/mL or PSA DT ≤ 10 months (mos) after the development of CRPC. The risk of subsequent BM was estimated for the overall cohort and for the CRPC and non-CRPC subsets. Results: The median age among patients in the study was 73 years, 48% were African American, and median f/u time after ADT initiation was 58 mos. 15% (n=93) met criteria for CRPC during f/u (with a median of 23 mos between ADT initiation and establishment of CRPC), with the majority considered being at high risk (n=81). Among the entire cohort, 74 men (10%) developed BM during f/u. The rate of BM was 4 times higher among CRPC patients compared to non-CRPC patients (p<0.001), with a median of 6 mos between CRPC and subsequent BM. No racial difference was observed with either the incidence of CRPC or BM. Conclusions: The HFHS resource allowed for investigation of disease progression in a racially diverse population. A substantial proportion of M0 PC patients on ADT will eventually develop CRPC and once castration-resistant, risk of BM is high.


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 : 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.


2010 ◽  
Vol 8 (2) ◽  
pp. 211-223 ◽  
Author(s):  
Philip J. Saylor ◽  
Matthew R. Smith

Androgen deprivation therapy (ADT) plays a central role in the management of men with locally advanced, recurrent, and metastatic prostate cancer. Because most men diagnosed with prostate cancer will die of something other than their cancer, treatment-related adverse effects are highly relevant to their long-term health. Benefits of ADT in each clinical setting must be weighed against ADT-related adverse effects. ADT is detrimental to several metabolic end points and to bone health. ADT has been prospectively shown to cause decreased lean muscle mass, increased fat mass, weight gain, increased cholesterol and triglycerides, insulin resistance, and loss of bone mineral density. In population-based analyses it has been associated with an increased incidence of diabetes, clinical fractures, and cardiovascular disease. Data-driven recommendations for managing these adverse effects are needed. Currently the authors advocate the use of adapted practice guidelines developed to prevent diabetes, fractures, and coronary heart disease in the general population.


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

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