Nursing Department, University of Valencia, 46010 Valencia, Spain.
Frailty Research Organized Group (FROG), University of Valencia, 46010 Valencia, Spain.
Biomolecules. 2023 Nov 13;13(11):1642. doi: 10.3390/biom13111642.
Androgen deprivation therapy (ADT) is a mainstay of prostate cancer in both adjuvant and palliative settings. Since androgens are crucial for functional status and psychological functions, we evaluated whether blood testosterone, androstenedione, or DHEA concentrations were associated with functional status and psychological alterations in patients with localised (PCa) or metastatic prostate cancer (mPCa) receiving ADT with analogues of luteinising hormone-releasing hormone (LHRH).
The five Fried criteria were considered to identify frailty syndrome. In addition, complementary evaluations were carried out to measure other variables of interest. Sleep quality was assessed using the Athens Insomnia Scale, cognitive functions were assessed using the Mini-Mental State Examination, and symptoms of depression were measured using the Yesavage Geriatric Depression Scale. Logistic regression analysis was performed to determine if the androgens level could be related to frailty syndrome, sleep impairment, depressive symptoms, and cognitive functions.
The results of the multivariate analyses show that high concentrations of androstenedione were significantly associated with frailty syndrome in both groups ( = 0.018; odds ratio = 4.66, 95% confidence interval [1.30-16.6]). There were significant relationships between frailty syndrome and the systemic concentration of androstenedione ( = 0.01), but not the concentration of testosterone ( = 0.60) or DHEA ( = 0.42). In addition, the results of the non-parametric tests show significant results between a decreased gait speed in the two groups (metastatic and localised) and the concentration of androstenedione ( = 0.015). High androstenedione levels were associated with a slow walking speed in the mCaP group ( = 0.016), while high testosterone levels were associated with a better walking speed in the localised CaP group ( = 0.03). For the concentration of androstenedione in plasma, the area under the curve was 0.72, with a 95% CI of 0.55-0.88 with acceptable values, and with a cut-off point of 4.51 pg/mL, a sensitivity of 82.9%, and specificity of 53.8%. No relationships between the concentration of androgens in plasma and sleep quality, cognitive functions, or symptoms of depression suggest that the changes were specific to frailty syndrome.
Further research into the role of androstenedione should be evaluated in follow-up studies in order to recommend its use as a suitable biomarker of frailty syndrome in prostate cancer patients.
雄激素剥夺疗法（ADT）是辅助和姑息治疗前列腺癌的主要方法。由于雄激素对于功能状态和心理功能至关重要，因此我们评估了局部前列腺癌（PCa）或转移性前列腺癌（mPCa）患者接受黄体生成素释放激素（LHRH）类似物 ADT 时，血液中的睾丸酮、雄烯二酮或 DHEA 浓度是否与功能状态和心理改变相关。
采用五个 Fried 标准来确定虚弱综合征。此外，还进行了补充评估以测量其他感兴趣的变量。使用雅典失眠量表评估睡眠质量，使用简易精神状态检查评估认知功能，使用 Yesavage 老年抑郁量表评估抑郁症状。进行逻辑回归分析以确定雄激素水平是否与虚弱综合征、睡眠障碍、抑郁症状和认知功能相关。
多变量分析的结果表明，高浓度的雄烯二酮与两组患者的虚弱综合征显著相关（ = 0.018；比值比 = 4.66，95%置信区间 [1.30-16.6]）。虚弱综合征与全身雄烯二酮浓度之间存在显著关系（ = 0.01），但与睾丸酮浓度（ = 0.60）或 DHEA 浓度（ = 0.42）无关。此外，非参数检验的结果表明，两组患者的步速降低与雄烯二酮浓度之间存在显著关系（ = 0.015）。高雄烯二酮水平与 mCaP 组的步行速度缓慢相关（ = 0.016），而高睾丸酮水平与局部 CaP 组的步行速度较快相关（ = 0.03）。对于血浆中雄烯二酮的浓度，曲线下面积为 0.72，95%CI 为 0.55-0.88，具有可接受的值，并且截断点为 4.51 pg/mL，灵敏度为 82.9%，特异性为 53.8%。血浆中雄激素浓度与睡眠质量、认知功能或抑郁症状之间没有关系，这表明这些变化是虚弱综合征的特异性变化。
应该在后续研究中进一步研究雄烯二酮的作用，以推荐其作为前列腺癌患者虚弱综合征的合适生物标志物。
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