ObjectiveTo report the protocol of a study evaluating the efficacy of transdermal oestradiol (E2) gel in reducing the adverse effects of androgen deprivation therapy (ADT), specifically on sexual function, and to assess the utility of E2 in combination with supervised exercise.Study Design and MethodsThe primary endpoint of this open‐label Phase IIA randomized controlled trial is the efficacy of transdermal E2 gel. Secondary endpoints include: (i) the occurrence of ADT‐induced adverse effects; (ii) the safety and tolerability of E2; (iii) the impact of E2 with or without exercise on physical, physiological, muscle, and systemic biomarkers; and (iv) quality of life. The trial will recruit high‐risk PCa patients (n = 310) undergoing external beam radiation therapy with adjuvant subcutaneous ADT. Participants will be stratified and randomized in a 1:1 ratio to either the E2 + ADT arm or the ADT‐only control arm. Additionally, a subset of patients (n = 120) will be randomized into a supervised exercise programme.ResultsThe primary outcome is assessed according to the efficacy of E2 in mitigating the deterioration of Expanded Prostate Cancer Index Composite sexual function domain scores. Secondary outcomes are assessed according to the occurrence of ADT‐induced adverse effects, safety and tolerability of E2, impact of E2 with or without exercise on physical performance, body composition, bone mineral density, muscle size, systematic biomarkers, and quality of life.ConclusionThe ESTRACISE study's innovative design can offer novel insights about the benefits of E2 gel, and the substudy can reinforce the benefits resistance training and deliver valuable new novel insights into the synergistic benefits of E2 gel and exercise, which are currently unknown.Trial RegistrationThe protocol has been registered in euclinicaltrials.eu (2023‐504704‐28‐00) and in clinicaltrials.gov (NCT06271551).

中文翻译：

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雄激素剥夺疗法中的透皮雌二醇和运动 (ESTRACISE)：方案

目的报告一项研究方案，评估透皮雌二醇 (E2) 凝胶在减少雄激素剥夺疗法 (ADT) 的副作用，特别是对性功能的副作用，并评估 E2 与监督运动相结合的效用。 研究设计和方法 这项开放标签 IIA 期随机对照试验的主要终点是透皮 E2 凝胶的功效。次要终点包括：(i) ADT 引起的不良反应的发生； (ii) E2 的安全性和耐受性； (iii) 有或没有运动的 E2 对身体、生理、肌肉和全身生物标志物的影响； (iv) 生活质量。该试验将招募高危 PCa 患者（n= 310) 接受外照射放射治疗并辅助皮下 ADT。参与者将以 1:1 的比例分层并随机分配到 E2 + ADT 组或仅 ADT 对照组。此外，一部分患者（n= 120）将被随机分配到监督锻炼计划中。 结果主要结果根据 E2 在减轻扩展前列腺癌指数综合性功能领域评分恶化方面的功效进行评估。次要结局根据ADT引起的不良反应的发生、E2的安全性和耐受性、有或没有运动的E2对身体表现、身体成分、骨矿物质密度、肌肉大小、系统生物标志物和生活质量的影响进行评估。结论 ESTRACISE 研究的创新设计可以提供关于 E2 凝胶益处的新颖见解，并且该子研究可以强化阻力训练的益处，并为目前未知的 E2 凝胶和运动的协同益处提供有价值的新见解。已注册于欧盟临床试验(2023‐504704‐28‐00) 和临床试验网（NCT06271551）。