SUN-120 - A Novel Rodent Model of Menopause-Related Hot Flashes for Therapeutic Drug Evaluation

Background
Hot flashes, or vasomotor symptoms (VMS), are a prevalent consequence of estrogen deficiency during the menopausal transition, significantly impaired the quality of life in menopausal women. They are characterized by a sudden surge in skin temperature, excessive sweating, facial flashing, and are often accompanied by increased heart rate, anxiety, and dizziness. Despite their profound impact, effective treatments remain limited. A major challenge in this field has been the lack of well-validated and reliable animal models and comprehensive assessment of body temperature change. In this study, we aim to establish a rodent model of hot flashes to support the preclinical drug discovery.
Methods
Female C57BL/6 mice and Sprague–Dawley rats were both used and randomly assigned to sham, ovariectomy (OVX), or estradiol-treated groups. Animals in the OVX and estradiol groups underwent bilateral ovariectomy, and following postoperative recovery the estradiol group received subcutaneous estradiol implantation. Thermoregulatory responses were assessed using graded-intensity treadmill running. After 3-4 weeks of training, tail-temperature changes were quantified using infrared thermal imaging.
Results
The integration of ovariectomy with treadmill training induced thermogenesis effectively recapitulated hot-flashes–like thermoregulatory phenotypes associated with menopause. As expected, ovariectomized mice and rats exhibited menopause-related symptoms such as weight gain, osteoporosis, and atrophy of reproductive organs. Following treadmill training, OVX animals showed significantly elevated tail temperatures relative to sham controls. Estradiol supplementation largely reversed these thermoregulatory abnormalities, supporting the role of hormone replacement therapy in treating hot flashes.
Conclusions
This approach establishes a practical and quantitative animal model for hot flashes monitoring and provides a useful platform for evaluating potential therapeutic interventions.