Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer

Keating, Nancy L.; O’Malley, A. James; Smith, Matthew R.

doi:10.1200/jco.2006.06.2497

Cited by 1,317 publications

(1,070 citation statements)

References 37 publications

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“…Epidemiological studies have implicated that ADT may be partly responsible for the increased number of CVD events, which is observed shortly after treatment initiation and most notably in patients with preexisting atherosclerotic CVD 4, 9. These observations are strongest for GnRH agonists, the most common form of ADT, whereas data on orchiectomy are less consistent and little information still exists pertaining to the newer GnRH antagonists 9, 26. In 2010, the combined observations led the U.S. Food and Drug Administration to put a warning label on GnRH agonists regarding the suspected increased risk of CVD (http://www.fda.gov/drugs/drugsafety/ucm229986.htm).…”

Section: Discussionmentioning

confidence: 99%

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

Poulsen

Mortensen

Koechling

et al. 2016

JAHA

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BackgroundTreatment of prostate cancer often involves androgen deprivation therapy (ADT) by gonadotropin‐releasing hormone (GnRH) receptor agonists, GnRH receptor antagonists, or orchiectomy. ADT may increase the rate of cardiovascular disease events, but recent clinical studies suggested that not all means of ADT carry the same risk, raising the possibility of non–testosterone‐mediated effects of different forms of ADT on atherosclerosis. Here we compared effects of ADT on atherosclerosis in intact and orchiectomized Apoe‐deficient mice.Methods and ResultsChow‐fed Apoe‐deficient mice were allocated to orchiectomy and/or monthly injections with the GnRH receptor agonist leuprolide or the GnRH receptor antagonist degarelix. Atherosclerosis was quantified at 26 weeks of age in the aortic arch by en face examination and in the aortic root by histology. In intact Apoe‐deficient mice, all types of ADT reduced testosterone production to castration levels. Although hypercholesterolemia was accentuated in leuprolide‐treated mice, the amount and composition of atherosclerosis was not different between the different types of ADT. In orchiectomized Apoe‐deficient mice, leuprolide, but not degarelix, augmented hypercholesterolemia, changed body, thymus, and spleen weights, and increased atherosclerosis in the aortic root. No direct effects of the drugs were detectable on cytokine secretion from murine bone marrow–derived macrophages or on splenocyte proliferation.ConclusionsNo differences in the development of atherosclerosis were detected among groups of intact Apoe‐deficient mice treated with different types of ADT. A pro‐atherogenic, possibly cholesterol‐mediated, effect of leuprolide was seen in orchiectomized mice that might be relevant for understanding the potential cardiovascular risk associated with GnRH agonist‐based ADT.

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Section: Discussionmentioning

confidence: 99%

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

Poulsen

Mortensen

Koechling

et al. 2016

JAHA

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“…Other studies also confirmed this connection between ADT, insulin resistance and hyperglycemia. 13,23,24 Although metabolic changes are sometimes neglected in the early phase, they can start as early as 3 months after treatment. Fasting insulin is a more sensitive index compared to fasting blood glucose.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Some of the complications have negative effects on quality of life assessments, while others may induce serious problems including myocardial infarction and sudden cardiac death. 13 A longterm study revealed that 53% of the deaths were not attributable to prostate cancer. Of these cases, cardiovascular problems are the predominant causes.…”

Section: Introductionmentioning

confidence: 99%

Androgen deprivation therapy through bilateral orchiectomy: increased metabolic risks

Jiang¹,

Zhang²,

Zhang³

et al. 2011

Asian J Androl

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Prostate cancer is one of the most common malignancies in men. Previous research has determined that androgen deprivation therapy (ADT) may be accompanied by an unfavourable metabolic profile. In this prospective study, 133 men were recruited, including 46 prostate cancer patients who had undergone bilateral orchiectomy and been on flutamide (the ADT group), 37 men with prostate cancer who had undergone radical prostatectomy (the non-ADT group) and 50 normal control subjects (the control group). All subjects were followed for at least 12 months. From baseline to 3 months, men in the ADT group had increased levels of fasting serum insulin and low-density lipoprotein compared to the other two groups (P,0.05). No obvious changes were found in the other parameters (P.0.05). After 12 months, men in the ADT group had increased levels of waist circumference, fasting serum insulin and glucose, total cholesterol, high-density lipoprotein and low-density lipoprotein compared to the other two groups (P,0.05). Additionally, the morbidity rate of metabolic syndrome in the ADT group was higher (P,0.05) compared to the other two groups. ADT through surgical castration for men with prostate cancer may be associated with unfavourable metabolic changes. The benefits of the therapy should be balanced prudently against these risks.

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“…[6][7][8] Furthermore, recent data have linked ADT to an increased risk of cardiovascular morbidity and mortality, including new onset diabetes, coronary artery disease and sudden cardiac death. [9][10][11][12] When ADT fails, patients with hormone-refractory PC have fewer treatment options and a poorer prognosis as the mainstay of therapy is cytotoxic chemotherapy that confers a mere 2-month survival advantage. 13 In recent years, increased attention has focused on exercise as a supportive adjunct therapy following a cancer diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Exercise therapy across the prostate cancer continuum

Antonelli

Freedland

Jones

2009

Prostate Cancer Prostatic Dis

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Exercise has been increasingly investigated as an adjunct therapy for cancer patients. The purpose of this paper is to comprehensively review the literature regarding exercise as a therapeutic adjunct for prostate cancer (PC). Several studies in patients with PC have shown quality of life improvements associated with exercise. Although no study has established the effect of exercise as a monotherapy for PC, the molecular mechanisms responsible for the potential association between exercise and PC are being elucidated. Given the low-risk, high-reward nature of these studies, further investigations are needed to better define the function of exercise along the PC continuum.

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Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer

Cited by 1,317 publications

References 37 publications

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

Androgen deprivation therapy through bilateral orchiectomy: increased metabolic risks

Exercise therapy across the prostate cancer continuum

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