Reproductive Hormones and Subclinical Cardiovascular Disease in Midlife Women

• Published in: The journal of clinical endocrinology and metabolism Vol. 103; no. 8; pp. 3070 - 3077
• Main Authors: Thurston, Rebecca C, Bhasin, Shalender, Chang, Yuefang, Barinas-Mitchell, Emma, Matthews, Karen A, Jasuja, Ravi, Santoro, Nanette
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.08.2018; Copyright Oxford University Press; Oxford University Press
• Subjects: 17β-Estradiol; Adult; Asymptomatic Diseases; Brachial Artery - physiology; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - epidemiology; Carotid artery; Carotid Intima-Media Thickness; Clinical s; Estradiol - blood; Estrogens; Estrone; Estrone - blood; Female; Gonadal Steroid Hormones - blood; Hormone replacement therapy; Humans; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Menopause - blood; Menopause - physiology; Middle Aged; Post-menopause; Postmenopause - blood; Regional Blood Flow; Regression analysis; Risk Factors; Scientific imaging; Sex hormones; Testosterone; Testosterone - blood; Vascular system; Vasodilation
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-00579

Abstract Context Reproductive hormones are important to the pathophysiology of cardiovascular disease (CVD) in women. However, standard estradiol (E2) and testosterone (T) assays lack sensitivity at the levels of postmenopausal women. Objective Investigate relations of mass spectrometry–assessed estrone (E1), E2, and T and SHBG and subclinical CVD in women. Design, Setting, and Participants Three hundred and four perimenopausal and postmenopausal women aged 40 to 60 years underwent subclinical CVD measurements. E1, E2, and T were assayed using liquid chromatography–tandem mass spectrometry; free T (FT) was estimated using ensemble allostery models. Regression models were adjusted for CVD risk factors. Main Outcome Measures Carotid artery intima media thickness, interadventitial diameter (IAD), and plaque; brachial flow mediated dilation (FMD). Results Higher E1 was related to higher FMD [β(SE) = 0.77 (0.37), P = 0.04], indicating better endothelial function. Higher E2 was related to lower IAD [β(SE) = −0.07 (0.02), P = 0.004], indicating less carotid remodeling. Higher SHBG was related to higher FMD [β(SE) = 1.31 (0.40), P = 0.001], yet higher IAD [β(SE) = 0.15 (0.06), P = 0.02] and plaque [OR (95% CI) = 1.84 (1.16 to 2.91), P = 0.009]; FT showed a similar yet inverse pattern of relations as SHBG. Thus, higher SHBG and lower FT were associated with better endothelial function, yet greater carotid remodeling and plaque. Conclusions Endogenous E1 levels were related to endothelial function and E2 to vascular remodeling, suggesting distinct roles of these estrogens. SHBG and FT have complex roles depending on the vessel under study. In midlife women, mass spectrometry–assessed estrone was related to endothelial function and estradiol to vascular remodeling. SHBG and free testosterone findings varied by vascular system.