Marchant Ivanny, Stojanova Jana, Acevedo Lilian, Olivero Pablo
Laboratorio de Modelamiento en Medicina, Escuela de Medicina, Universidad de Valparaíso, Viña del Mar; Centro Interoperativo en Ciencias Odontológicas y Médicas, Universidad de Valparaíso, Valparaíso, Chile.
Laboratorio de Modelamiento en Medicina, Escuela de Medicina; Interdisciplinary Centre for Health Studies (CIESAL), Universidad de Valparaíso, Viña del Mar, Chile.
Neural Regen Res. 2022 Aug;17(8):1629-1632. doi: 10.4103/1673-5374.332121.
Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective effects. Hormone therapy has been widely used to treat menopausal estrogen deficiency for more than 80 years. Despite high initial expectations of cardioprotective effects, there has been substantial distrust following important randomized clinical trials, such as the Women's Health Initiative. Subsequently, the timing of treatment in relation to the onset of menopause came under consideration and led to the proposal of the timing hypothesis, that early initial treatment is important, and benefits are lost as the timing since menopause becomes prolonged. Subsequent analyses of the Women's Health Initiative data, together with more recent data from randomized and observational trials, consistently show reductions in coronary heart disease and mortality in younger menopausal women. Regarding cognitive function, the timing hypothesis is consistent with observations from basic and animal studies. There is some clinical evidence to support the benefits of hormonal therapy in this context, though skepticism remains due to the paucity of clinical trials of substantial length in younger menopausal women. It is likely that the effects of estrogens on cognitive performance are due to rapid mechanisms, including mechanisms that influence Ca homeostasis dynamics, provide protection in a hostile environment and reduce inflammatory signals from neural tissues. In the future, inflammatory profiles accounting for early signs of pathological inflammation might help identify the 'window of opportunity' to use estrogen therapy for successful cognitive protection.
雌激素对健康的神经组织有多种有益作用，并具有心脏保护作用。激素疗法已被广泛用于治疗绝经后雌激素缺乏症达80多年。尽管最初对其心脏保护作用寄予厚望，但在诸如妇女健康倡议等重要的随机临床试验之后，出现了大量的不信任。随后，开始考虑治疗时间与绝经开始时间的关系，并由此提出了时机假说，即早期开始治疗很重要，且随着绝经后时间的延长，益处会丧失。对妇女健康倡议数据的后续分析，以及来自随机试验和观察性试验的最新数据，一致表明年轻绝经后女性的冠心病和死亡率有所降低。关于认知功能，时机假说与基础研究和动物研究的观察结果一致。在这种情况下，有一些临床证据支持激素疗法的益处，不过由于针对年轻绝经后女性的长期临床试验较少，怀疑态度依然存在。雌激素对认知表现的影响可能归因于快速作用机制，包括影响钙稳态动态、在不利环境中提供保护以及减少神经组织炎症信号的机制。未来，能够解释病理性炎症早期迹象的炎症特征可能有助于确定使用雌激素疗法实现成功认知保护的“机会窗口”。
