The Influence of Age at Natural Menopause on Cerebrovascular Reactivity

Abstract

The onset of menopause coincides with a loss of the vasoprotective effects of estrogen. Early menopause is associated with increased cardiovascular risk factors and cardiovascular disease; however, the specific cerebrovascular outcomes regarding the timing at natural menopause are not understood. The purpose of this study was to investigate how the age of natural menopause influences cerebrovascular reactivity, a measure of cerebrovascular function. We studied 37 women with earlier (Early; n = 20; age at onset of menopause = 46 ± 3 y; age at time of study = 61 ± 4 y) and later (Late; n = 17; age at onset of menopause = 55 ± 2 y; age at time of study = 62 ± 3 y) onset of natural menopause. Supine brachial blood pressure was taken in triplicate using a sphygmomanometer before study procedures. Middle cerebral artery velocity (MCAv), mean arterial blood pressure (MAP), and end‐tidal carbon dioxide (ETCO□) were continuously recorded during hypercapnia to measure cerebrovascular reactivity. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. Reactivity was calculated as the slope of the relationship between ETCO□ and each variable of interest. There were no significant differences in MCAv reactivity (Early: 2.0 ± 0.2 cm/s/mmHg; Late: 2.3 ± 0.2 cm/s/mmHg; p = 0.09), MAP reactivity (Early: 1.0 ± 0.3 mmHg/mmHg; Late: 1.0 ± 0.2 mmHg/mmHg; p = 0.50), or CVCi reactivity (Early: 0.01 ± 0.002 cm/s/mmHg2; Late: 0.02 ± 0.001 cm/s/mmHg2; p = 0.16) between women who experienced an earlier or later onset of menopause. However, the Early and Late groups had a statistically significant difference in supine brachial MAP at rest (Early: 99.5 ± 1.9 mmHg, Late: 91.6 ± 2.9 mmHg; p < 0.05), which may confound cerebrovascular reactivity to hypercapnia. When brachial MAP was added as a covariate, the Early group had a significantly lower MCAv reactivity (p < 0.05) than the Late group. These results suggest that the age at natural menopause may influence cerebrovascular function in postmenopausal women, as women who experience an earlier onset of menopause have lower cerebrovascular reactivity after resting MAP is accounted for. Future studies should examine intervention strategies, such as menopausal hormone therapy, in order to mitigate these discrepancies in cerebral blood flow regulation.Support or Funding InformationResearch funded through a grant from the Alzheimer’s Association.