Androgen Deprivation Therapy and Cardiovascular Risk

University of California, San Francisco, Department of Urology, 1600 Divisadero St, Box 1695, San Francisco, CA 94143-1695, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 08/2011; 29(26):3510-6. DOI: 10.1200/JCO.2011.35.1494
Source: PubMed


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.
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.
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.
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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    • "However, clinical data concerning ADT-related adverse metabolic and cardiovascular effects remain conflicting [4]. There have been studies demonstrating that patients receiving ADT may have a higher incidence of diabetes mellitus [5] [6] [7], coronary artery disease [5] [6], stroke [6] [7], and/or even cardiovascular death [8] [9] [10], but other studies failed to show such associations [7] [11] [12]. This may be due to the fact that, in these studies, the presence of preexisting metabolic condition and other cardiovascular diseases had not been adequately characterized and/or controlled. "
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    ABSTRACT: Background. Androgen deprivation therapy (ADT) in nonmetastatic prostate cancer is unclear. Recent data suggests possible increase in the cardiovascular risks receiving ADT. The aim of the study was to investigate the cardiovascular outcomes in a cohort of Chinese nonmetastatic prostate cancer patients with no previously documented cardiovascular disease. Methods and Results. 745 patients with no previously documented cardiovascular disease and/or diabetes mellitus diagnosed to have nonmetastatic prostate cancer were recruited. Of these, 517 patients received ADT and the remaining 228 did not. After a mean follow-up of 5.3 years, 60 patients developed primary composite endpoint including (1) coronary artery disease, (2) congestive heart failure, and (3) ischemic stroke. Higher proportion of patients on ADT (51 patients, 9.9%) developed composite endpoint compared with those not on ADT (9 patients, 3.9%) with hazard ratio (HR) of 2.06 (95% confidence interval (CI): 1.03-3.24, P = 0.04). Furthermore, Cox regression analysis revealed that only the use of ADT (HR: 2.1, 95% CI: 1.03-4.25, P = 0.04) and hypertension (HR: 2.0, 95% CI: 1.21-3.33, P < 0.01) were independent predictors for primary composite endpoint. Conclusion. ADT in Chinese patients with nonmetastatic prostate cancer with no previously documented cardiovascular disease was associated with subsequent development of cardiovascular events.
    Full-text · Article · Apr 2014 · Journal of Oncology
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    • "Testosterone is the fundamental steroid hormone that drives prostate growth but there is no proven evidence that T treatment may convert subclinical PCa to clinically detectable PCa (Rhoden and Averbeck, 2009; Jannini et al., 2011). After 3-to 6- months of treatment, ADT is known to cause metabolic imbalance, i.e., increase in fat mass, insulin resistance, hyperlipidemia, metabolic syndrome (Braga-Basaria et al., 2006), and/or full-blown diabetes mellitus, loss of bone mass, and fractures (Grossmann and Zajac, 2011), as well as increased cardiovascular risk, anemia , and loss of muscle (Punnen et al., 2011). All these metabolic changes put patients at an increased risk of cerebrovascular events, such as ischemic strokes and transient ischemic attacks, causing a significant increased risk of cardiovascular death (Levine et al., 2010). "
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    ABSTRACT: Androgen deprivation therapy (ADT) for prostate carcinoma (PCa) may cause cardiometabolic complications unless intermittent androgen blockade (IAB) is instituted. An 80-year-old caucasian man was diagnosed intermediate grade (Gleason 4 + 3) PCa and was treated with continuous ADT with triptorelin plus bicalutamide. After 6 months of treatment, he experienced an acute myocardial infarction and 1 month after hospitalization he came to our outpatient clinic for fatigue, weight gain, and hyperglycemia. Due to iatrogenic hypogonadism, we decided to proceed with IAB, but after 3 months ADT withdrawal his serum testosterone (T) was still 0.5 ng/mL. Due to very low concomitant PSA levels (0.1 ng/mL) he was then proposed intermittent T-gel supplementation (Tostrex(®)) which was initiated according to the following scheme: 6 months on and 3 months off. T-gel dose was titrated tri-weekly in order to achieve T plasma levels below 3.49 ng/mL. After 6 months on, his serum T raised to a mean value of about 2.0 ng/mL without increments in PSA. After overall 12 months on, his serum T peaked to a mean value of 3.0 ng/mL while a delay in PSA rise was seen after 24 months (0.6 ng/mL) but remained stable until the last observation carried forward (LOCF), at 45 months. No clinical and biochemical PCa progression were observed at LOCF. Reversion of iatrogenic metabolic syndrome started after 6 months of T supplementation without using any add-on treatment. This case provides support that once regression of PCa growth is attained, T supplementation may be administered in well differentiated PCa, especially if IAB is not successful in reverting iatrogenic hypogonadism and its associated cardiac and metabolic complications.
    Full-text · Article · Feb 2012 · Frontiers in Endocrinology
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    ABSTRACT: The knowledge of secondary effects of androgen deprivation has improved. Besides hot flushes and erectile dysfunction, cardiovascular and bone complications must be taken into consideration once medication has been indicated and also during treatment. The onset of diabetes can occur early, within six months after the start of treatment, with dyslipidaemia being far rarer. An increase in the frequency of cardiovascular events and cardiac mortality remains controversial. There is now sufficient evidence to show that androgen deprivation moderately increases the risk of osteoporotic-type bone disorders. A greater understanding of the secondary effects will require an initial clinical and paraclinical study, as well as the monitoring of longterm hormone therapy.
    No preview · Article · Feb 2012 · Oncologie
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