Year: 2021
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Several forms of pulmonary hypertension (PH) disproportionately affect women. Animal and human studies suggest that estradiol exerts mixed effects on the pulmonary vasculature. Whether premature menopause represents a risk factor for PH is unknown. METHODS AND FINDINGS: In this cohort study, women in the UK Biobank aged 40-69 years who were postmenopausal and had complete data available on reproductive history were included. Premature menopause, defined as menopause occurring before age 40 years. Postmenopausal women without premature menopause served as the reference group. The primary outcome was incident PH, ascertained by appearance of a qualifying ICD code in the participant's UK Biobank study record. Of 136,715 postmenopausal women included, 5,201 (3.8%) had premature menopause. Participants were followed up for a median of 11.1 (interquartile range 10.5-11.8) years. The primary outcome occurred in 38 women (0.73%) with premature menopause and 409 (0.31%) without. After adjustment for age, race, ever-smoking, body-mass index, systolic blood pressure, antihypertensive medication use, non-high-density lipoprotein cholesterol, cholesterol-lowering medication use, C-reactive protein, prevalent type 2 diabetes, obstructive sleep apnea, heart failure, mitral regurgitation, aortic stenosis, venous thromboembolism, forced vital capacity (FVC), the forced expiratory volume in 1 second-to-FVC ratio, use of menopausal hormone therapy, and hysterectomy status, premature menopause was independently associated with PH (hazard ratio 2.13, 95% CI 1.31-3.23, P<0.001). In analyses of alternate menopausal age thresholds, risk of PH appeared to increase progressively with younger age at menopause (Ptrend <0.001), with 4.8-fold risk in women with menopause before age 30 years (95% CI 1.82-12.74, P = 0.002). Use of menopausal hormone therapy did not modify the association of premature menopause with PH. CONCLUSIONS: Premature menopause may represent an independent risk factor for PH in women. Further investigation of the role of sex hormones in PH is needed in animal and human studies to elucidate pathobiology and identify novel therapeutic targets.
Source: PLoS ONE
Institutions: Broad Institute, Harvard University, Massachusetts General Hospital, Massachusetts Institute of Technology, Richard L. Roudebush VA Medical Center, Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, Vertex Pharmaceuticals (United States)
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,749
Awards: G1189786236, G1234744102, G1289036858, G1299449749, G147578628, G2040566396, G2096033943, G2185488700, Clonal hematopoiesis in humans: determinants of development and progression, G2581677850, G2808718245, G3271462333, G3792973439, Eicosanoid Profiles as Determinants of HFpEF, G426421887, G5086259594, G5240891896, G5712819311, G5850737185, G603018768, G6062545421, G6227055320, G6354290783, G7004738603, G7299544143, G7723204790, G7887376495, G8272672485, G871831658, Clonal hematopoiesis and atherosclerosis, Clonal Hematopoiesis in the Women's Health Initiative
OpenAlex ID: W3134774187