There is ample empirical evidence to support the notion that the biological impacts of estrogen extend beyond the gonads to other bodily systems, including the brain and behavior. Converging preclinical findings have indicated a neuroprotective role for estrogen in a variety of experimental models of cognitive function and brain insult. However, the surprising null or even detrimental findings of several large clinical trials evaluating the ability of estrogen-containing hormone treatments to protect against age-related brain changes and insults, including cognitive aging and brain injury, led to hesitation by both clinicians and patients in the use of exogenous estrogenic treatments for nervous system outcomes. That estrogen-containing therapies are used by tens of millions of women for a variety of health-related applications across the lifespan has made identifying conditions under which benefits with estrogen treatment will be realized an important public health issue. Here we provide a summary of the biological actions of estrogen and estrogen-containing formulations in the context of aging, cognition, stroke, and traumatic brain injury. We have devoted special attention to highlighting the notion that estrogen appears to be a conditional neuroprotectant whose efficacy is modulated by several interacting factors. By developing criteria standards for desired beneficial peripheral and neuroprotective outcomes among unique patient populations, we can optimize estrogen treatments for attenuating the consequences of, and perhaps even preventing, cognitive aging and brain injury.

有充足的经验证据支持这样的观点：雌激素的生物学影响超越性腺，延伸到其他身体系统，包括大脑和行为。临床前研究结果表明，雌激素在各种认知功能和脑损伤的实验模型中具有神经保护作用。然而，几项大型临床试验评估了含雌激素的激素治疗预防与年龄相关的大脑变化和损伤（包括认知衰老和脑损伤）的能力，得出了令人惊讶的无效甚至有害的结果，导致临床医生和患者犹豫不决。使用外源性雌激素治疗神经系统的结果。数以千万计的女性在整个生命周期中将含雌激素的疗法用于各种与健康相关的应用，这使得确定实现雌激素治疗益处的条件成为一个重要的公共卫生问题。在这里，我们总结了雌激素和含雌激素制剂在衰老、认知、中风和创伤性脑损伤方面的生物作用。我们特别关注强调雌激素似乎是一种有条件的神经保护剂，其功效受到多种相互作用因素的调节。通过为独特的患者群体制定所需的有益外周和神经保护结果的标准，我们可以优化雌激素治疗，以减轻甚至预防认知衰老和脑损伤的后果。