PDF(Pubmed)
Abstract：
Menopausal women may experience symptoms of depression, sometimes even progressing clinical depression requiring treatment to improve quality of life. While varying levels of estrogen in perimenopause may contribute to an increased biological vulnerability to mood disturbances, the effectiveness of estrogen replacement therapy (ERT) in the relief of depressive symptoms remains controversial. Menopausal depression has a complex, multifactorial etiology, that has limited the identification of optimal treatment strategies for the management of this psychiatric complaint. Nevertheless, clinical evidence increasingly supports the notion that estrogen exerts neuroprotective effects on brain structures related to mood regulation. Indeed, research using preclinical animal models continues to improve our understanding of menopause and the effectiveness of ERT and other substances at treating depression-like behaviors. However, questions regarding the efficacy of ERT in perimenopause have been raised. These questions may be answered by further investigation using specific animal models of reduced ovarian function. This review compares and discusses the advantages and pitfalls of different models emulating the menopausal stages and their relationship with the onset of depressive-like signs, as well as the efficacy and mechanisms of conventional and novel ERTs in treating depressive-like behavior. Ovariectomized young rats, middle-to-old aged intact rats, and females treated with reprotoxics have all been used as models of menopause, with stages ranging from surgical menopause to perimenopause. Additionally, this manuscript discusses the impact of organistic and therapeutic variables that may improve or reduce the antidepressant response of females to ERT. Findings from these models have revealed the complexity of the dynamic changes occurring in brain function during menopausal transition, reinforcing the idea that the best approach is timely intervention considering the opportunity window, in addition to the careful selection of treatment according to the presence or absence of reproductive tissue. Additionally, data from animal models has yielded evidence to support new promising estrogens that could be considered as ERTs with antidepressant properties and actions in endocrine situations in which traditional ERTs are not effective.
摘要：
更年期女性可能会出现抑郁症状，有时甚至进展为临床抑郁症，需要治疗以提高生活质量。虽然围绝经期雌激素水平的变化可能会增加对情绪障碍的生物学易感性，雌激素替代疗法(ERT)在缓解抑郁症状方面的有效性仍存在争议.更年期抑郁症有一个复杂的，多因素病因，这限制了确定最佳治疗策略来管理这种精神病性投诉。然而，临床证据越来越支持雌激素对与情绪调节相关的大脑结构具有神经保护作用的观点。的确,使用临床前动物模型的研究继续提高我们对更年期以及ERT和其他物质治疗抑郁症样行为的有效性的理解.然而,有人质疑ERT在围绝经期的疗效.这些问题可以通过使用卵巢功能降低的特定动物模型的进一步研究来回答。这篇综述比较并讨论了模拟更年期阶段的不同模型的优点和陷阱及其与抑郁样体征发作的关系，以及常规和新型ERT治疗抑郁样行为的功效和机制。去卵巢幼鼠,中老年完整的老鼠，接受再生毒素治疗的女性都被用作更年期的模型，从手术绝经到围绝经期不等。此外,本手稿讨论了可能改善或减少女性对ERT的抗抑郁反应的器官和治疗变量的影响.这些模型的研究结果揭示了更年期过渡期间脑功能动态变化的复杂性，强化了这样一种观点，即考虑到机会窗口，最好的方法是及时干预，除了根据生殖组织的存在或不存在仔细选择治疗方法。此外,来自动物模型的数据已经产生了支持新的有希望的雌激素的证据,这些雌激素可以被认为是在传统ERT无效的内分泌情况下具有抗抑郁特性和作用的ERT.
