(134) Early Impact of Androgen Deprivation Therapy on Endothelial Function and Metabolic Parameters in Prostate Cancer Patients: A Prospective Study

Abstract

Androgen deprivation therapy (ADT) is considered one of the mainstays in the treatment of prostate cancer. ADT slows cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these proven benefits, this treatment is related to several side effects, such as increased cardiovascular risk, changes in body composition and various metabolic changes. Although the well-established association between circulating testosterone level and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. This study aimed to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery and measurement of serum inflammatory markers. It was also our aim to evaluate the early impact of ADT on body composition and metabolic parameters. We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to December 2022 at our institution. Smokers and those who quit smoking less than five years ago, decompensated diabetics (glycated hemoglobin > 9%) and those who had already had a cardiovascular event were excluded. High-resolution B-mode ultrasound was used to assess vascular diameter and endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. Our metabolic and inflammatory profile included measurement of serum total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein and assessment of body fat distribution through bioelectrical impedance. Subjects were evaluated at baseline and 3 months after starting ADT with goserelin acetate 10.80 mg. A total of 32 men were included. The mean age was 69 years and the prevalence of diabetes was 31.25%. FMD demonstrated a worsening trend after ADT, which did not reach statistical significance after 3 months (mean 3.39 ± 6.83 vs 1.16 ± 7.65; p = 0.14) (figure 1). Baseline brachial artery diameter also showed a tendency to worsen with ADT compared to baseline (0.44 ± 0.06 vs 0.42 ± 0.06; p = 0.06). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting glucose (mean 104.10 ± 18.96 vs 110.60 ± 25.29; p = 0.01), fasting insulin levels (mean 13.05 ± 8.76 vs 16.82 ± 11.36; p = 0.003), glycated hemoglobin (mean 5.89% ± 0.46 vs 6.15% ± 0.67; p = 0.008) and homeostatic model assessment insulin resistance (mean 3.47 ± 2.55 vs 5.05 ± 4.50; p = 0.005) increased significantly after 3 months. Triglycerides concentrations (mean 142.30 ± 69.66 vs 165.50 ± 93.04; p = 0.03) were higher after 3 months of ADT. Abdominal circumference (mean 98.66 ± 10.16 vs 99.76 ± 9.39; p = 0.02) and body mass index (mean 27.46 ± 4.06 vs 27.76 ± 3.89; p = 0.02) also increased after ADT. Although not statistically significant, the present study demonstrated a trend towards a decrease in brachial artery FMD. We also observed 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. No.