Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, PSC-502, Los Angeles, California 90033, USA.
Endocrinology. 2012 Aug;153(8):3571-8. doi: 10.1210/en.2012-1340. Epub 2012 Jul 9.
Increasing importance is placed on the translational validity of animal models of human menopause to discern risk vs. benefit for prediction of outcomes after therapeutic interventions and to develop new therapeutic strategies to promote health. Basic discovery research conducted over many decades has built an extensive body of knowledge regarding reproductive senescence across mammalian species upon which to advance animal models of human menopause. Modifications to existing animal models could rapidly address translational gaps relevant to clinical issues in human menopausal health, which include the impact of 1) chronic ovarian hormone deprivation and hormone therapy, 2) clinically relevant hormone therapy regimens (cyclic vs. continuous combined), 3) clinically relevant hormone therapy formulations, and 4) windows of opportunity and optimal duration of interventions. Modifications in existing animal models to more accurately represent human menopause and clinical interventions could rapidly provide preclinical translational data to predict outcomes regarding unresolved clinical issues relevant to women's menopausal health. Development of the next generation of animal models of human menopause could leverage advances in identifying genotypic variations in estrogen and progesterone receptors to develop personalized menopausal care and to predict outcomes of interventions for protection against or vulnerability to disease. Key to the success of these models is the close coupling between the translational target and the range of predictive validity. Preclinical translational animal models of human menopause need to keep pace with changes in clinical practice. With focus on predictive validity and strategic use of advances in genetic and epigenetic science, new animal models of human menopause have the opportunity to set new directions for menopausal clinical care for women worldwide.
越来越重视将人类绝经的动物模型的转化有效性用于辨别治疗干预后的风险与益处，以开发新的治疗策略来促进健康。几十年来进行的基础发现研究为推进人类绝经的动物模型奠定了广泛的哺乳动物生殖衰老知识基础。对现有动物模型的修改可以快速解决与人类绝经健康临床问题相关的转化差距，其中包括以下几个方面：1）慢性卵巢激素剥夺和激素治疗的影响，2）临床相关的激素治疗方案（周期性与连续联合），3）临床相关的激素治疗制剂，以及 4）干预的机会窗口和最佳持续时间。对现有动物模型的修改以更准确地代表人类绝经和临床干预，可以快速提供临床前转化数据，以预测与女性绝经健康相关的未解决临床问题的结果。开发下一代人类绝经的动物模型可以利用鉴定雌激素和孕激素受体基因变异的进展，制定个性化的绝经护理，并预测预防或易患疾病的干预措施的结果。这些模型成功的关键是转化目标与预测有效性范围之间的紧密结合。人类绝经的临床前转化动物模型需要跟上临床实践的变化。通过关注预测有效性和对遗传和表观遗传科学进展的战略应用，人类绝经的新动物模型有机会为全球妇女的绝经临床护理设定新的方向。
