{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:53:07Z","timestamp":1781013187395,"version":"3.54.1"},"reference-count":40,"publisher":"American Physiological Society","issue":"6","funder":[{"name":"NIH\/RMR VA Medical Center","award":["R01AG027678"],"award-info":[{"award-number":["R01AG027678"]}]},{"name":"NIH\/RMR VA Medical Center","award":["P30DK048520"],"award-info":[{"award-number":["P30DK048520"]}]},{"name":"NIH\/UC Denver iC42 Clinical Research and Development Center","award":["K01AG20683"],"award-info":[{"award-number":["K01AG20683"]}]},{"name":"NIH","award":["5T32HL007171"],"award-info":[{"award-number":["5T32HL007171"]}]},{"name":"NIH","award":["P50HD073063"],"award-info":[{"award-number":["P50HD073063"]}]},{"name":"NIH\/UC Denver Center for Women's Health Research\/RMR VA Medical Center GRECC","award":["R01Ag027678\/R56HL114073"],"award-info":[{"award-number":["R01Ag027678\/R56HL114073"]}]},{"name":"MOJ\/NCATS Colorado CTSA","award":["UL1TR001082"],"award-info":[{"award-number":["UL1TR001082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:p>Hyperhomocysteinemia is associated with endothelial dysfunction and increased cardiovascular disease (CVD). We determined whether elevated homocysteine (Hcy) and markers of Hcy metabolism were associated with the previously reported endothelial dysfunction across stages of the menopause transition. Brachial artery flow-mediated dilation (FMD) and plasma concentrations of Hcy, cysteine, and methionine were measured in healthy women ( n = 128) 22\u201370 yr of age categorized as premenopausal ( n = 35), perimenopausal (early: n = 16; late: n = 21), and postmenopausal (early: n = 21; late: n = 35). Dietary intake of micronutrients involved in Hcy metabolism (e.g., vitamins B6, B12, folate) was assessed in a subpopulation of women. Hcy and cysteine concentrations were progressively higher, and methionine was progressively lower across menopausal stages (all P &lt; 0.005). The higher Hcy and cysteine concentrations correlated with lower circulating estradiol levels ( r\u2009=\u2009\u22120.49 and \u22120.50, respectively, both P &lt; 0.001). FMD was inversely correlated with Hcy ( r\u2009=\u2009\u22120.25, P = 0.004) and cysteine ( r\u2009=\u2009\u22120.39, P &lt; 0.001) and positively correlated with methionine concentrations ( r\u2009=\u20090.25, P = 0.005). Dietary intake of vitamins B6 and B12 (both P &lt; 0.05) were lower in postmenopausal women. Vitamin B12 intake correlated with FMD ( r\u2009=\u20090.22, P = 0.006). These data suggest that declines in estradiol across stages of the menopause transition may lead to elevations in Hcy and cysteine that may contribute to endothelial dysfunction in postmenopausal women. Future studies should examine whether targeting Hcy metabolism during the perimenopausal to early postmenopausal period with interventions, including diet, attenuates or reverses the decline in endothelial function in women.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Declines in circulating estradiol across the stages of the menopausal transition may lead to elevations in Hcy and cysteine concentrations that may contribute to endothelial dysfunction. Abnormalities in the Hcy metabolic pathways, possibly related to dietary deficiencies of vitamins B12 and B6 and folate, may contribute to elevations in Hcy and cysteine concentrations. Findings also suggest that higher cysteine levels may be more damaging to the vascular endothelium than Hcy.<\/jats:p>","DOI":"10.1152\/japplphysiol.00819.2018","type":"journal-article","created":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T14:28:32Z","timestamp":1553178512000},"page":"1533-1540","source":"Crossref","is-referenced-by-count":26,"title":["Elevated plasma homocysteine and cysteine are associated with endothelial dysfunction across menopausal stages in healthy women"],"prefix":"10.1152","volume":"126","author":[{"given":"Amy C.","family":"Keller","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado"},{"name":"Denver Veterans Affairs Medical Center, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7463-7811","authenticated-orcid":false,"given":"Kerry L.","family":"Hildreth","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Christians","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Putnam","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy M.","family":"Kohrt","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado"},{"name":"Denver Veterans Affairs Medical Center Geriatric Research Education and Clinical Center, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E. 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