{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:53:10Z","timestamp":1788483190134,"version":"build-2803163510"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Sex hormones play a role in pulmonary arterial hypertension (PAH), but the menstrual cycle has never been studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We conducted a prospective observational study of eight women with stable PAH and 20 healthy controls over one cycle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Participants completed four study visits 1 week apart starting on the first day of menstruation. Relationships between sex hormones, hormone metabolites, and extracellular vesicle microRNA (miRNA) expression and clinical markers were compared with generalized linear mixed modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Women with PAH had higher but less variable estradiol (E2) levels (P\u2009&amp;lt;\u20090.001) that tracked with 6-minute walk distance (P\u2009&amp;lt;\u20090.001), N-terminal prohormone of brain natriuretic peptide (P\u2009=\u20090.03) levels, and tricuspid annular plane systolic excursion (P\u2009&amp;lt;\u20090.01); the direction of these associations depended on menstrual phase. Dehydroepiandrosterone sulfate (DHEA-S) levels were lower in women with PAH (all visits, P\u2009&amp;lt;\u20090.001). In PAH, each 100-\u03bcg\/dl increase in DHEA-S was associated with a 127-m increase in 6-minute walk distance (P\u2009&amp;lt;\u20090.001) and was moderated by the cardioprotective E2 metabolite 2-methoxyestrone (P\u2009&amp;lt;\u20090.001). As DHEA-S increased, N-terminal prohormone of brain natriuretic peptide levels decreased (P\u2009=\u20090.001). Expression of extracellular vesicle miRNAs-21, -29c, and -376a was higher in PAH, moderated by E2 and DHEA-S levels, and tracked with hormone-associated changes in clinical measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Women with PAH have fluctuations in cardiopulmonary function during menstruation driven by E2 and DHEA-S. These hormones in turn influence transcription of extracellular vesicle miRNAs implicated in the pathobiology of pulmonary vascular disease and cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.202006-671oc","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T11:47:50Z","timestamp":1599220070000},"page":"218-228","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":26,"title":["Insights from the Menstrual Cycle in Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"18","author":[{"given":"Grayson L.","family":"Baird","sequence":"first","affiliation":[{"name":"Lifespan Hospital System, Providence, Rhode Island"},{"name":"Department of Diagnostic Imaging and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2620-6843","authenticated-orcid":false,"given":"Thomas","family":"Walsh","sequence":"additional","affiliation":[{"name":"Lifespan Hospital System, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Aliotta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Allahua","sequence":"additional","affiliation":[{"name":"Lifespan Hospital System, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Andrew","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Bourjeily","sequence":"additional","affiliation":[{"name":"Lifespan Hospital System, Providence, Rhode Island"},{"name":"Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Brodsky","sequence":"additional","affiliation":[{"name":"Department of Pathology, Rhode Island Hospital and Lifespan Hospital System, Alpert Medical School of Brown University, and Center for Computational Molecular Biology, Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Denver","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, Queen\u2019s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom"},{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Dooner","sequence":"additional","affiliation":[{"name":"Lifespan Hospital System, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth O.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Vascular Research Laboratory, Providence Veterans Affairs Medical Center, Providence, Rhode Island; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Klinger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret R.","family":"MacLean","sequence":"additional","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Mullin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Pereira","sequence":"additional","affiliation":[{"name":"Lifespan Hospital System, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena","family":"Poppas","sequence":"additional","affiliation":[{"name":"Lifespan Hospital System, Providence, Rhode Island"},{"name":"Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Whittenhall","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4223-4775","authenticated-orcid":false,"given":"Corey E.","family":"Ventetuolo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island"},{"name":"Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, Rhode Island"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"2026012203464991300_bib1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/0002-9343(51)90020-4","article-title":"Primary pulmonary hypertension. 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