Conventional androgen deprivation therapy is associated with an increased risk of cardiovascular disease in advanced prostate cancer, a nationwide population-based study

Li, Jian-Ri; Wang, Shian‐Shiang; Chen, Chuan-Shu; Cheng, Chen-Li; Hung, Sheng-Chun; Lin, Ching‐Heng; Chiu, Kun‐Yuan

doi:10.1371/journal.pone.0270292

Cited by 5 publications

(2 citation statements)

References 39 publications

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“…Concomitant comorbidities were assessed during preoperative medical history interviews by both experienced anesthesiologists and urologists. Subsequently, the short-term major postoperative complications were grouped into categories, namely arterial hypertonia, elevated blood fat levels, diabetes mellitus, cardiovascular disease, chronic pulmonary disease, chronic kidney disease, other cancer, mental disorder, and neurologic disease, based on previous publications as defined in Supplementary Table S1 [25][26][27][28][29]. Furthermore, obesity was defined as a BMI greater than or equal to 30.…”

Section: Definition Of Variables For Analysesmentioning

confidence: 99%

Cardiovascular Disease and Chronic Pulmonary Disease Increase the Risk of Short-Term Major Postoperative Complications after Robotic-Assisted Radical Prostatectomy

Siech,

Gruber,

Wenzel

et al. 2024

Medicina

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Background and objectives: Certain comorbidities may be associated with a higher risk of complications after robotic-assisted radical prostatectomy. Material and Methods: Relying on a tertiary care database, we identified robotic-assisted radical prostatectomy patients (January 2014–March 2023). Short-term major postoperative complications were defined according to Clavien Dindo as ≥IIIa within 30 days after robotic-assisted radical prostatectomy. Results: Of 1148 patients, the rates of postoperative Clavien Dindo IIIa, Clavien Dindo IIIb, Clavien Dindo IVa, and Clavien Dindo IVb complications were 3.3%, 1.4%, 0.3%, and 0.2%, respectively. Of those, 28 (47%) had lymphoceles, and 8 (13%) had bleeding-associated complications. Patients with cardiovascular disease (8 vs. 4%) or chronic pulmonary disease (13 vs. 5%) were more likely to have complications. In multivariable logistic regression models, cardiovascular disease (odds ratio: 1.78; p = 0.046) and chronic pulmonary disease (odds ratio: 3.29; p = 0.007) remained associated with an increased risk of postoperative complications. Conclusions: Complications after robotic-assisted radical prostatectomy are predominantly manageable without anesthesia. Concomitant cardiovascular disease and chronic pulmonary disease were both associated with a higher risk of postoperative complications.

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Section: Definition Of Variables For Analysesmentioning

confidence: 99%

Cardiovascular Disease and Chronic Pulmonary Disease Increase the Risk of Short-Term Major Postoperative Complications after Robotic-Assisted Radical Prostatectomy

Siech,

Gruber,

Wenzel

et al. 2024

Medicina

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“…Apart from BPH, the association between the serum balance of androgens with age and its link to prostate cancer risk has become a topic of immense research interest, especially in men above 40 years [12,13]. In 2018, about 1.3 million new cases were recorded and over 350,000 deaths were as a result of prostate cancer [14].…”

Section: Introductionmentioning

confidence: 99%

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Saah

Sakyi

Adu-Poku

et al. 2023

Journal of Chemistry

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Steroid 5 alpha-reductase 2 (5αR-2) is a membrane-embedded protein that together with other isoforms plays a key role in the metabolism of steroids. This enzyme catalyzes the reduction of testosterone to the more potent ligand, dihydrotestosterone (DHT) in the prostate. Androgens, testosterone, and DHT play important roles in prostate growth, development, and function. At the same time, both testosterone and DHT have been implicated in the pathogenesis of benign prostate hyperplasia (BPH). Inhibition of the DHT formation, therefore, provides a therapeutic strategy that offers the possibility of preventing, delaying, or treating BPH. Currently, two steroidal drugs that inhibit 5αR-2, dutasteride and finasteride, have been approved for clinical use. These two come at a high cost and also portray undesirable sexual side effects which necessitate the need to find new chemotherapeutic alternatives for the disease. Based on the aforementioned, finasteride and dutasteride were subjected to scaffold hopping, fragment-based de novo design, molecular docking, and molecular dynamics simulations employing databases like ChEMBL, DrugBank, PubChem, ChemSpider, and Zinc15 in the identification of potential hits targeting 5αR-2. Altogether, ten novel compounds targeting 5αR-2 were identified with binding energies lower or comparable to finasteride and dutasteride, the main inhibitors for this target. Molecular docking and molecular dynamics simulations studies identify amino acid residues Glu57, Phe219, Phe223, and Leu224 to be critical for ligand binding and complex stability. The physicochemical and pharmacological profiling suggests the potential of the hit compounds to be drug-like and orally active. Similarly, the quality parameter assessments revealed the hits possess LELP greater than 3 implying their promise as lead-like molecules. The compounds A5, A9, and A10 were, respectively, predicted to treat prostate disorders with Pa (0.188, 0.361, and 0.270) and Pi (0.176, 0.050, and 0.093), while A8 and A9 were found to be associated with BPH treatment with Pa (0.09 and 0.127) and Pi (0.077 and 0.033), respectively. Structural similarity searches via DrugBank identified the drugs faropenem, acemetacin, estradiol valerate, and yohimbine to be useful for BPH treatment suggesting the de novo designed ligands as potential chemotherapeutic agents for treating this disease.

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Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network

Merseburger,

Bakshi,

Chen

et al. 2024

World J Urol

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Purpose Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). Methods The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. Results The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists’ practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. Conclusion In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

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Conventional androgen deprivation therapy is associated with an increased risk of cardiovascular disease in advanced prostate cancer, a nationwide population-based study

Cited by 5 publications

References 39 publications

Cardiovascular Disease and Chronic Pulmonary Disease Increase the Risk of Short-Term Major Postoperative Complications after Robotic-Assisted Radical Prostatectomy

Cardiovascular Disease and Chronic Pulmonary Disease Increase the Risk of Short-Term Major Postoperative Complications after Robotic-Assisted Radical Prostatectomy

Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment

Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network

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