Age at natural menopause impacts cerebrovascular reactivity and brain structure

Abstract

Menopause is associated with adverse changes in vascular health coinciding with an increased risk of stroke and vascular cognitive impairment. However, there is significant variation in the age at menopause. The present study examined how the age at natural menopause impacts cerebrovascular reactivity and structural biomarkers of brain aging. Thirty-five healthy postmenopausal women were classified as early onset menopause (Early; n = 19, age at menopause: 47 ± 2 years) or later onset menopause (Late; n = 16, age at menopause: 55 ± 2 years). Middle cerebral artery blood velocity (MCAv), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO₂) were recorded during a stepped hypercapnia protocol. Reactivity was calculated as the slope of the relationship between ETCO₂ and each variable of interest. Brain volumes and white matter hyperintensities (WMH) were obtained with 3T MRI. Resting MAP was greater in the Early group (99 ± 9 mmHg) compared with the Late group (90 ± 12 mmHg; P = 0.02). Cerebrovascular reactivity, assessed using MCAv, was blunted in the Early group (1.87 ± 0.92 cm/s/mmHg) compared to the Late group (2.37 ± 0.75 cm/s/mmHg; P = 0.02). Total brain volume did not differ between groups (Early: 1.08 ± 0.07L vs. Late: 1.07 ± 0.06L; P = 0.66), but the Early group demonstrated greater WMH fraction compared with the Late group (Early: 0.36 ± 0.14% vs. Late: 0.25 ± 0.14%; P = 0.02). These results suggest that age at natural menopause impacts cerebrovascular function and WMH burden in healthy postmenopausal women.

Associations of Cerebrovascular Regulation and Arterial Stiffness With Cerebral Small Vessel Disease: A Systematic Review and Meta‐Analysis

“… 51 , 52 , 53 , 58 , 63 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 75 , 77 , 78 , 80 , 81 , 83 , 86 , 87 , 91 The remaining 18 studies were prospective or retrospective cohort studies. 54 , 55 , 56 , 57 , 59 , 62 , 72 , 73 , 74 , 76 , 79 , 82 , 84 , 85 , 92 , 93 , 94 , 95 In 203 patients with leukoaraiosis, Bian et al 91 demonstrated that patients exhibiting more severe white matter hyperintensities (Fazekas grades II and III) had a significantly reduced cerebrovascular reactivity compared with those with lower severity. In another larger cohort study, Staszewski et al 58 reported that in 120 subjects, the lowest tertile of cerebrovascular reactivity had a 19‐fold greater likelihood of having cSVD compared with the highest tertile.…”

A mini-review of the evidence for cerebrovascular changes following gender-affirming hormone replacement therapy and a call for increased focus on cerebrovascular transgender health

“…While some studies report reduced CBF and CVR following menopause, high-quality evidence and consistent menopausal criteria are lacking (Ruediger et al, 2021). A confounding factor is the impact of age and physical fitness at menopause age on cerebrovascular health (Chen et al, 2023;Moir et al, 2023;Ruediger et al, 2023). A recent systematic review of the influence of sex hormones on cerebrovascular function in human subjects suggested that, though there were often differences between high and low hormonal states, the directions were not consistent (Skinner et al, 2021).…”

Age at Natural Menopause and Influencing Factors in Women Attending the Gynecological Outpatient Clinic at a Tertiary Care Hospital

“…According to several studies, premature or early menopause is linked to cardiovascular disease, osteoporosis, type 2 diabetes, early cognitive function impairment, lower life expectancy, and increased mortality from all causes. [6][7][8][9][10][11][12][13] There are slight variations in the onset of natural menopause between ethnic groups, which are strongly influenced by genetics. 2,14 Other studies have shown that it is affected by ethnicity, region, and geographical country.…”