(297) Evaluation of Endothelial Function and Metabolic Profile in Patients with Prostate Cancer Undergoing Androgen Deprivation Therapy
Authors: Cintra A R , Linhares B L , Da Rocha E L , Linhares-Filho J , Da Trindade K M , Monteiro M M F , Lopes M D S R , Palmeira H T , Da Silva M J , Bessa J , Miranda E P , Reges R 
Published: May 2023

Abstract

Introduction
Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the therapy comes with known side effects, such as increased cardiovascular adverse events and metabolic changes. Despite the well-established association between the level of circulating testosterone and endothelial integrity, the direct effects of ADT on endothelial function remain controversial.

Objective
The aim of the present study was to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery, and the measurement of serum inflammatory markers. It was also our goal to evaluate early impact of ADT on anthropometric and metabolic parameters

Methods
We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to July 2022 at our institution. Patients with decompensated diabetes mellitus (HbA1c &gt;9%), active smokers or smokers who have ceased for less than 5 years and those with confirmed diagnosis of peripheral artery disease, coronary artery disease, angina, congestive heart failure, myocardial infarction, coronary revascularization or stroke, were excluded. Brachial artery assessment included vascular diameter and flow-mediated (endothelium-dependent) vasodilation (FMD) using high-resolution B-mode ultrasound. Our metabolic and inflammatory profile included serum measurement of total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein, and bioimpedance assessment of body fat distribution. All measurements were performed at baseline and after 3 months of ADT initiation with goserelin acetate 10.80mg.

Results
A total of 14 men with mean age of 67.9 ± 6.9 years were included. The prevalence of diabetes in the present cohort was 21.4%. FMD demonstrated a slight increase following ADT, which did not reach statistical significance after 3 months (median 2.2% vs. 5.0%; p = 0.8224 – Figure 1). Baseline brachial artery diameter significantly decreased with ADT compared to baseline (median diameter 0.43cm vs 0.40cm; p = 0.006). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting insulin levels (mean 9.67 ± 6.09 vs 13.19 ± 7.47; p = 0.002), glycated hemoglobin (mean 5.79% ± 0.47 vs 6.22% ± 0.75; p = 0.009) and homeostatic model assessment insulin resistance increased significantly after 3 months (p = 0.006). Low-density lipoprotein cholesterol (mean 112.00 ± 27.35 vs 128.90 ± 29.00; p = 0.01) and triglycerides (mean 145.40 ± 78.52 vs 168.20 ± 105.80; p = 0.03) concentrations were higher after 3 months of ADT. No significant differences were found in body fat distribution.

Conclusions
Although the present study has not demonstrated a significant change in brachial artery FMD, we verified an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events.

Disclosure
No