Central obesity and progressive vascular and cognitive complications in a long-term mouse model of post-menopause

Background: Post-menopause is associated with an increased risk of cardiometabolic complications and cognitive decline. Over 70% of women who went through menopause have never received any treatment. Thus, postmenopausal women are at high risk of facing severe health problems. Preclinical studies have largely utilized ovariectomy as a murine model of short-term post-menopause. Studies evaluating long-term post-menopause effects on cardiometabolism and cognition remain limited. We hypothesize that if left untreated, a prolonged post-menopausal state can exacerbate metabolic and cardiovascular dysfunction as well as cognitive impairment. Methods: Ovariectomy (OVX), a surgical removal of the ovaries, was utilized as a model to study the effects of long-term post-menopause in mice. C57BL/6 female mice (14 weeks old) were randomly assigned into two groups: Sham (n=16) or Postmenopausal (n=10). Following 78 weeks post-OVX, body weight, abdominal circumference, intracarotid pulse wave velocity (icPWV), a gold standard for arterial stiffness, pulsatility index (a measure of vascular resistance), and cognitive performance using the novel object recognition test (NORT) were analyzed. Results: Long-term postmenopausal mice exhibited increased body weight (26.39 ± 0.38 g vs. 22.56 ± 0.27 g Sham, p<0.05) and abdominal circumference (8.75 ± 0.30 cm vs. 7.80 ± 0.26 cm Sham, p<0.05), characterizing central obesity. Progressive arterial stiffness (icPWV: 13.25 ± 0.70 m/s vs. 8.67 ± 0.86 m/s Sham, p<0.05) was accompanied by increased pulsatility index (1.54 ± 0.05 vs 1.28 ± 0.07 Sham, p<0.05), indicating a significant impairment in vascular function. NORT results showed a progressive decline in recognition memory after 18 weeks (preference index: 42% vs. 72% Sham, p<0.05) and 57 weeks (preference index: 13% vs. 56% Sham, p<0.05) post-OVX. Conclusion: These findings imply that, if left untreated, long-term post-menopause leads to central obesity and progressive vascular and cognitive problems. NIH-NHLBI This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.