How preclinical models of menopause can inform clinical care: A focus on midlife and reciprocal communication between clinical and preclinical science

Midlife in women typically includes the menopausal transition, a time of hormonal transformation, adaptation, and reorganization. Coincident with this dynamic period of physiological change, there are putatively modifiable factors that influence disease, short-term and long-term health outcomes, symptom emergence, and longevity. The menopause transition could be considered a window of vulnerability; however, it is also a window of opportunity for intervention. Thus, the menopause transition is a critical sensitive window whereby there is opportunity for turning points for healthy aging trajectories. Preclinical research can aid in this pursuit of scientific discovery for modifiable factors and treatments, and their particular parameters. Rodent menopause models include surgical and transitional variations, allowing detection of precise determinants impacting menopause-related outcomes. These models permit systematic manipulation of endogenous and exogenous hormone exposures across the lifespan, with infinite outcome measurements ranging from molecular to behavioral. This research is uniquely poised to address complex, interactive hypotheses with extensive control in a relatively short timeframe, including dissociation of age and menopause effects. To understand the many dynamic changes with menopause, iterative and reciprocal communication between clinical and preclinical domains of science is key. •Midlife is a time of hormonal transformation, including the menopausal transition.•Finding health determinants of the menopausal transition can yield mediations toward healthy aging.•The menopausal transition is a sensitive period for vulnerabilities and for intervention.•Preclinical menopause models permit systematic manipulation of health determinants across the lifespan.•Reciprocal communication between clinical and preclinical research is key for maximum progress.