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Late-Onset Menopause Attenuates Aortic Stiffness in the Postmenopausal Period.

Sanna Darvish1, Kevin O Murray1, Sophia A Mahoney1

  • 1Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO (S.D., K.O.M., S.A.M., N.S.V., M.C.Z., C.A., M.A.F., D.R.S., M.J.R.).

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Summary

Later menopause (≥55 years) is linked to reduced cardiovascular disease risk. This study found attenuated aortic stiffening in late-onset postmenopausal women, suggesting a mechanism for this protective effect.

Keywords:
agingcardiovascular diseasesmenopausemitochondriaoxidative stressvascular stiffnesswomen

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Area of Science:

  • Cardiovascular Physiology
  • Reproductive Endocrinology
  • Vascular Biology

Background:

  • Later age at menopause (≥55 years) is associated with reduced cardiovascular disease (CVD) risk in postmenopausal women (PMW).
  • Aortic stiffening is a key contributor to CVD risk, but its relationship with late-onset menopause remains unclear.

Purpose of the Study:

  • To investigate the impact of late-onset menopause on aortic stiffness in postmenopausal women.
  • To determine the contributions of structural and load-dependent factors to aortic stiffness in relation to menopause onset age.

Main Methods:

  • Carotid-femoral pulse wave velocity (PWV_CF) was measured in late-onset (≥55 years) and normal-onset (45-54 years) PMW.
  • Structural- and load-dependent PWV_CF components were calculated using exponential models.
  • Aortic ring elastic modulus was assessed in mice exposed to PMW serum, with lipidomics identifying stiffness drivers.

Main Results:

  • PWV_CF was significantly lower (128 cm/s) in late-onset PMW compared to normal-onset PMW.
  • The majority of this reduction (≈85%) was attributed to lower structural-dependent stiffness, not blood pressure load.
  • Lower elastic modulus in aortas exposed to late-onset PMW serum was linked to reduced mitochondrial reactive oxygen species-dependent stiffness, with triglyceride (16:0) identified as a key driver.

Conclusions:

  • Attenuated aortic stiffening, primarily through reduced structural-dependent factors, may explain the lower CVD risk observed in women with late-onset menopause.
  • These findings highlight potential mechanisms linking reproductive aging to vascular health and cardiovascular risk.