University of Arizona School of Medicine, Division of Integrative Medicine, Tucson, LA.
Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, LA.
Mayo Clin Proc. 2021 Dec;96(12):3130-3141. doi: 10.1016/j.mayocp.2021.08.009. Epub 2021 Nov 2.
Estradiol (E2) plays an underrecognized role in modulating body-wide systems, including important interactions with the renin-angiotensin-aldosterone system (RAAS). The RAAS is an immunomodulating system that is critical for maintaining homeostasis across multiple organ systems. The diverse interactions between E2 and the RAAS help maintain cardiometabolic homeostasis, including successful physiologic responses to trauma and infectious pathogens. Estradiol deficiency (ie, menopause) results in impaired responses and increased susceptibility to infectious pathogens. Both immune and cardiometabolic function decline with reduced E2 production, in part because the RAAS becomes dysregulated by E2 deficiency, leaving RAAS predominantly in its proinflammatory state and predisposing to systemic low-grade inflammation. Estradiol deficiency and RAAS dysregulation contribute to impaired immune responses and increased incidence of cardiac hypertrophy, hypertension, atherosclerotic cardiovascular disease, arrhythmias, and heart failure. The RAAS consists of dual, counterbalancing pathways-proinflammatory and anti-inflammatory. Estradiol is a signaling agent that plays a major role in determining which RAAS pathway predominates. The proinflammatory pathway is activated early in response to infection or trauma, followed by up-regulation of the anti-inflammatory pathway, to resolve inflammation and to restore homeostasis. Estradiol influences activation of the "switch" to restore the anti-inflammatory state. The dysregulated RAAS is a primary target of current cardiovascular therapeutics focused on blocking portions of its proinflammatory pathway. However, RAAS-modifying pharmaceuticals often provide imperfect solutions to these physiologic disruptions and underscore the need for improved approaches to menopausal medicine. Estradiol therapy and optimal lifestyle practices combined with RAAS-modifying pharmaceuticals may be an ideal strategy to optimize postmenopausal health.
雌二醇（E2）在调节全身系统中发挥着未被充分认识的作用，包括与肾素-血管紧张素-醛固酮系统（RAAS）的重要相互作用。RAAS 是一种免疫调节系统，对于维持多个器官系统的内稳态至关重要。E2 和 RAAS 之间的多种相互作用有助于维持心脏代谢内稳态，包括对创伤和感染病原体的成功生理反应。雌二醇缺乏（即绝经）导致反应受损和对感染病原体的易感性增加。由于 E2 缺乏导致 RAAS 失调，RAAS 主要处于促炎状态，容易发生全身低度炎症，因此免疫和心脏代谢功能会随着 E2 产生减少而下降。雌二醇缺乏和 RAAS 失调导致免疫反应受损和心脏肥大、高血压、动脉粥样硬化性心血管疾病、心律失常和心力衰竭的发生率增加。RAAS 由双重、相互平衡的途径——促炎和抗炎途径组成。E2 是一种信号分子，在决定哪种 RAAS 途径占主导地位方面起着重要作用。促炎途径在感染或创伤后早期被激活，随后抗炎途径上调，以解决炎症并恢复内稳态。E2 影响激活“开关”以恢复抗炎状态。失调的 RAAS 是当前心血管治疗的主要靶点，这些治疗方法侧重于阻断其促炎途径的部分。然而，RAAS 调节药物通常不能完美地解决这些生理紊乱问题，这突显了需要改进绝经医学方法的必要性。雌二醇治疗和最佳生活方式实践与 RAAS 调节药物联合使用可能是优化绝经后健康的理想策略。
