Complex Metabolic and Skeletal Changes in Men Taking Long-Term Androgen Deprivation Therapy

Žiaran, Stanislav; Gonçalves, F.; Sn, Jan Breza

doi:10.1016/j.clgc.2012.08.005

Cited by 17 publications

(9 citation statements)

References 38 publications

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“…Thus, there may be residual confounding affecting the analysis of those on anti-androgen monotherapy. Alterations in lipid levels may be another mechanism through which systemic ADT is propagating risk of TED [26][27][28][29][30]. Our dataset does not contain information on any of these factors and thus further mechanistic studies are required to determine if these do play a role in the associations observed.…”

Section: Discussionmentioning

confidence: 99%

Risk of thromboembolic disease in men with prostate cancer undergoing androgen deprivation therapy

et al. 2015

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ObjectivesTo investigate the risk of thromboembolic disease (TED) in men with prostate cancer (PCa) on androgen deprivation therapy (ADT), while accounting for known TED risk factors. Materials and MethodsWe assessed TED risk for 42 263 men with PCa who were receiving ADT compared with a matched cohort of 190 930 without PCa. The associations between ADT and deep vein thrombosis (DVT) or pulmonary embolism (PE) were analysed using multivariate Cox proportional hazard regression models, while accounting for previous PCa-related surgeries and the following proxies for disease progression: transurethral resection of the prostate, palliative radiotherapy and nephrostomy. ResultsBetween 1997 and 2013, 11 242 men with PCa received antiandrogen monotherapy, 26 959 men received gonadotropinreleasing hormone (GnRH) agonists, 1 091 men received combined androgen blockade and 3 789 men underwent orchiectomy. When accounting for previous surgeries and proxies of disease progression, GnRH agonist users and surgically castrated men had a higher risk of TED than the comparison cohort: hazard ratios (HRs) 1.67 (95% confidence interval [CI] 1.40-1.98) and 1.61 (95% CI 1.15-2.28), respectively. Men on anti-androgen monotherapy had a lower risk: HR for DVT 0.49 (95% CI 0.33-0.74). TED risk was highest among those who switched from anti-androgen to GnRH agonists: HR for PE 2.55 (95% CI 1.76-3.70). This increased from 2.52 (95% CI 1.54-4.12) in year 1, to 4.05 (95% CI 2.51-6.55) in year 2. ConclusionThe incidence of TED among men on ADT increased with the duration of therapy and the risk was highest for those who switched regimen, suggesting that disease progression as well as ADT contribute to the propagation of TED risk. Nonetheless, these findings support the hypothesis that only men with a relevant indication should receive systemic ADT.

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Section: Discussionmentioning

confidence: 99%

Risk of thromboembolic disease in men with prostate cancer undergoing androgen deprivation therapy

et al. 2015

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“…However, as these studies did not measure hip circumference, it is unclear if the increases represented a preferential accumulation of abdominal fat mass or were more representative of a global increase in adiposity. In 95 men treated with ADT, Ziaran and coworkers (Ziaran et al 2013) reported a 7.5% and 12% increase in waist-tohip ratio over the first 12 and 24 months of treatment, respectively, suggesting that there is a preferential accumulation of abdominal fat mass. However, these results need to be interpreted with caution as the waist-tohip ratio cannot differentiate between absolute changes in fat mass and lean tissue mass.…”

Section: Android and Gynoid Adipositymentioning

confidence: 99%

“…Observations from short-term administration of ADT (<12 weeks) have demonstrated variable effects on plasma glucose, with some studies showing significant increases (Smith et al 2006) and others showing no change (Smith et al 2001, Dockery et al 2003. Longitudinal studies with follow-up periods beyond 12 months have shown 5-10% increases in fasting glucose (Ziaran et al 2013, Morote et al 2015. Although studies investigating changes in HbA1c have shown little to no change in HbA1c during the first 6-12 months of ADT (Smith et al 2006, Phillips et al 2014, Morote et al 2015, given that changes in plasma glucose do not tend to appear until at least 12 months of treatment, studies with longer follow-up periods may be required to adequately assess the effect of ADT on this measure.…”

Section: Insulin Resistance and Glucose Regulationmentioning

confidence: 99%

The clinical importance of quantifying body fat distribution during androgen deprivation therapy for prostate cancer

Foulkes

Daly

2017

Endocrine-Related Cancer

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Androgen deprivation therapy (ADT) is now considered a mainstay in the treatment of metastatic and locally advanced prostate cancer (PCa). Despite well-established benefits of ADT in relation to overall survival, this treatment has been associated with a number of adverse effects, particularly with regard to key cardiometabolic risk factors including the development of insulin resistance, dyslipidemia and increases in total and regional fat mass. In non-ADT populations, increased levels of visceral adipose tissue (VAT) are thought to be a key mediator of the increased cardiometabolic risk associated with weight gain, but this has received limited attention in men treated with ADT. VAT is best assessed using tools such as computed tomography or magnetic resonance imaging; however, these tools are not readily accessible for the majority of researchers or clinicians. Recent advances allow for a method of estimating VAT using a whole-body dual-energy X-ray absorptiometry (DXA) scan that shows promise as a practical tool for researchers to evaluate changes in body fat distribution during ADT. The aim of this narrative review is to (1) review the available evidence with regard to the relationship between ADT and cardiometabolic risk; (2) discuss the role of body fat distribution on cardiometabolic risk in non-ADT populations, with a particular emphasis on the importance of visceral adiposity; (3) examine the potential influence of ADT on body fat distribution and visceral adiposity and (4) provide an overview of current tools used to measure changes in body fat distribution in men treated with ADT, highlighting the potential utility of a recently developed DXA-derived measure of VAT.

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“…Although numerous research studies have been conducted on the relationship between the use of ADT and BMD reduction [9,10,11,16,17,18,19,20,21,22], there has not been a systematic review and meta-analysis of this topic in existing literature. Therefore, we conducted this study as a systematic review of published literature and meta-analysis of available data in order to evaluate the change in BMD in patients with PCa receiving ADT compared to those who did not receive ADT.…”

Section: Introductionmentioning

confidence: 99%

Effect of Androgen-Deprivation Therapy on Bone Mineral Density in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis

Kim

Lee

Kim

et al. 2019

JCM

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We aimed to evaluate the change in bone mineral density (BMD) in patients with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) compared to those with PCa or other urologic conditions not receiving ADT. Literature searches were conducted throughout October 2018. The eligibility of each study was assessed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the Participant, Intervention, Comparator, Outcome, and Study design method. The outcomes analyzed were the mean difference (MD) of percent changes in BMD of lumbar spine, femur neck, and total hip. Five prospective cohort studies with a total of 533 patients were included in the present study. Statistically significant decreases of BMD change relative to the control group were observed in the ADT treatment group in the lumbar spine (MD −3.60, 95% CI −6.72 to −0.47, P = 0.02), femoral neck (MD −3.11, 95% CI −4.73 to −1.48, P = 0.0002), and total hip (MD −1.59, 95% CI −2.99 to −0.19, P = 0.03). There is a significant relationship between ADT and BMD reduction in patients with PCa. Regular BMD testing and the optimal treatment for BMD loss should, therefore, be considered in patients with PCa undergoing ADT.

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Complex Metabolic and Skeletal Changes in Men Taking Long-Term Androgen Deprivation Therapy

Cited by 17 publications

References 38 publications

Risk of thromboembolic disease in men with prostate cancer undergoing androgen deprivation therapy

Risk of thromboembolic disease in men with prostate cancer undergoing androgen deprivation therapy

The clinical importance of quantifying body fat distribution during androgen deprivation therapy for prostate cancer

Effect of Androgen-Deprivation Therapy on Bone Mineral Density in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis

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