Menopause, hormone therapy and cognition: maximizing translation from preclinical research

Abstract

Menopause-associated and hormone-associated cognitive research has a rich history built from varied disciplines and species. This review discusses landmark rodent and human work addressing cognitive outcomes associated with varied experiences of menopause and hormone therapy. Critical variables in menopause and cognitive aging research are considered, including menopause etiology, background hormone milieu and parameters of exposure to estrogens and progestogens. Recent preclinical research has identified that menopause and ovarian hormone fluctuations across many neurobiological systems affect cognitive aging, mapping novel avenues for future research. Preclinical models provide insight into complex interdisciplinary relationships in a systematic and highly controlled fashion. We highlight that acknowledging the strengths and weaknesses for both preclinical and clinical research approaches is vital to accurate interpretation, optimal translation and the direction of future research. There is great value in collaboration and communication across preclinical and clinical realms, especially regarding reciprocal feedback of findings to advance preclinical models, improve experimental designs and enrich basic science translation to the clinic. In searching for biological mechanisms underlying the cognitive consequences of menopause and hormone therapies, it is noteworthy that clinical and preclinical scientists are grounded in the same fundamental goal of optimizing health outcomes for women across the lifespan.

摘要

绝经和激素相关的认知研究有着丰富的历史, 建立在不同的学科和物种上。本综述讨论了具有里程碑意义的啮齿动物和人类工作, 涉及认知与绝经和激素治疗的不同经历相关的结果。绝经和认知老化研究的关键变量包括绝经病因学、背景激素环境和雌激素和孕激素暴露参数。最近的临床前研究已经确定, 绝经和卵巢激素的波动在许多神经生物学系统影响认知老化, 绘制了未来研究的新途径。临床前模型以系统和高度可控的方式提供了对复杂的跨学科关系的洞察力。我们强调, 承认临床前和临床研究方法的优缺点对准确解释、最佳翻译和未来研究方向至关重要。临床前和临床领域的合作和交流具有重要的价值, 特别是在研究结果的交互反馈方面, 可以改进临床前模型, 改进实验设计, 丰富基础科学向临床的转化。值得注意的是, 在寻找绝经期和激素疗法认知后果的生物学机制时, 临床和临床前科学家都以优化妇女一生健康结果这一基本目标为基础。

Keywords:

• Menopause
• hysterectomy
• ovariectomy
• hormone therapy
• aging
• memory
• rat
• female

Potential conflict of interest

The authors report no potential conflict of interest.

Additional information

Funding

Arizona Department of Health Sciences [ADHS14-052688]; US Department of Health and Human Services, National Institutes of Health, National Institute on Aging [AG028084], [F31AG056110]; US Department of Health and Human Services, National Institutes of Health [P30AG019610].