Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer

Corona, Giovanni; Filippi, Sandra; Bianchi, Nicola; Dicuio, Mauro; Rastrelli, Giulia; Concetti, Sergio; Sforza, Alessandra; Maggi, Mario

doi:10.5534/wjmh.200109

Cited by 14 publications

(12 citation statements)

References 66 publications

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“…In fact, the consistent demonstration in those studies of no higher prostate cancer‐specific mortality 8 – 10 suggests that differences in all-cause mortality are associated with patients’ factors unrelated to prostate cancer. On the other hand, differences between surgical and radiation primary therapies in combined treatment with adjuvant androgen deprivation, associated with certain complications 26 , 27 , could partially explain this higher mortality risk.…”

Section: Discussionmentioning

confidence: 99%

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

Suárez

Vigués²,

Castells³

et al. 2022

Sci Rep

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To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with 125I brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan–Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making.Study identifier at ClinicalTrials.gov: NCT01492751.

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Section: Discussionmentioning

confidence: 99%

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

Suárez

Vigués²,

Castells³

et al. 2022

Sci Rep

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“…The high occurrence of prostate cancer and the implication of the AR signaling in its growth [ 124 , 138 ] resulted in the need to find drugs able to sustain most of the anabolic and protein-protective functions of T because of the limited (or counterproductive) benefits of T deprivation [ 139 , 140 , 141 , 142 ]. These efforts resulted in the development of a large number of selective AR modulators (SARM) [ 143 , 144 ].…”

Section: Mechanisms Of Action Of Androgensmentioning

confidence: 99%

The Roles of Androgens in Humans: Biology, Metabolic Regulation and Health

Alemany

2022

IJMS

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Androgens are an important and diverse group of steroid hormone molecular species. They play varied functional roles, such as the control of metabolic energy fate and partition, the maintenance of skeletal and body protein and integrity and the development of brain capabilities and behavioral setup (including those factors defining maleness). In addition, androgens are the precursors of estrogens, with which they share an extensive control of the reproductive mechanisms (in both sexes). In this review, the types of androgens, their functions and signaling are tabulated and described, including some less-known functions. The close interrelationship between corticosteroids and androgens is also analyzed, centered in the adrenal cortex, together with the main feedback control systems of the hypothalamic–hypophysis–gonads axis, and its modulation by the metabolic environment, sex, age and health. Testosterone (T) is singled out because of its high synthesis rate and turnover, but also because age-related hypogonadism is a key signal for the biologically planned early obsolescence of men, and the delayed onset of a faster rate of functional losses in women after menopause. The close collaboration of T with estradiol (E2) active in the maintenance of body metabolic systems is also presented Their parallel insufficiency has been directly related to the ravages of senescence and the metabolic syndrome constellation of disorders. The clinical use of T to correct hypoandrogenism helps maintain the functionality of core metabolism, limiting excess fat deposition, sarcopenia and cognoscitive frailty (part of these effects are due to the E2 generated from T). The effectiveness of using lipophilic T esters for T replacement treatments is analyzed in depth, and the main problems derived from their application are discussed.

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“…Signs of poor glycemic control were detected within the first 3 months under ADT and seemed to worsen as the treatment progressed. Patients with preexisting diabetes presented higher levels of glycosylated hemoglobin (HbA1c) at follow-up blood tests [21]. Thus, longer treatment duration with ADT was associated with higher risk for developing diabetes [22,23,24].…”

Section: Metabolic Side Effects and Body Compositionmentioning

confidence: 99%

Cardiometabolic side effects of androgen deprivation therapy in prostate cancer

Lafontaine

Kokorovic

2022

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of reviewAndrogen-deprivation therapy (ADT) is widely employed for treatment of advanced prostate cancer and it is considered the frontline therapy. However, the numerous adverse reactions associated with this treatment option are concerning and its potential association with cardiovascular diseases (CVD) should not be overlooked. In this review, we examine the literature on the cardiovascular side effects of ADT and the physiologic mechanisms underpinning the association with CVD. We will also specifically discuss the different findings regarding the interesting potential disparity in major cardiovascular events among GnRH agonist-treated patients compared with patients undergoing GnRH antagonist treatment.Recent findingsAndrogen-deprivation therapy increases the risk of developing CVD by altering the body composition, metabolism, vascular system, and cardiac physiology. GnRH agonists may pose a higher risk of cardiovascular mortality and morbidity than GnRH antagonists; however, this link remains to be determined. Furthermore, screening for cardiovascular risk factors before and during ADT treatment is a crucial step in preventing major adverse cardiac events in prostate cancer patients. Notably, preexisting CVD and comorbidities have been identified as major key elements predicting cardiovascular events. Early implementation of pharmacological and nonpharmacological treatment strategies is strongly suggested, and regular follow-up visits should be scheduled to continuously assess patients’ cardiovascular risk under ADT.SummaryADT is a very powerful treatment option for advanced prostate cancer that improves survival outcomes but has the potential of considerably impacting patients’ cardiovascular health. Medical optimization and close monitoring are crucial during treatment with ADT.

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Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer

Cited by 14 publications

References 66 publications

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study

The Roles of Androgens in Humans: Biology, Metabolic Regulation and Health

Cardiometabolic side effects of androgen deprivation therapy in prostate cancer

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