{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T23:11:54Z","timestamp":1784157114962,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010HL141268"],"award-info":[{"award-number":["R01\u2010HL141268"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01-HL141268"],"award-info":[{"award-number":["R01-HL141268"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) remains life\u2010limiting despite numerous approved vasodilator therapies. Right ventricular (RV) function determines outcome in PAH but no treatments directly target RV adaptation. PAH is more common in women, yet women have better RV function and survival as compared to men with PAH. Lower levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester are associated with more severe pulmonary vascular disease, worse RV function, and mortality independent of other sex hormones in men and women with PAH. DHEA has direct effects on nitric oxide (NO) and endothelin\u20101 (ET\u20101) synthesis and signaling, direct antihypertrophic effects on cardiomyocytes, and mitigates oxidative stress. Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) is an on\u2010going randomized double\u2010blind placebo\u2010controlled crossover trial of DHEA in men (<jats:italic>n<\/jats:italic>\u2009=\u200913) and pre\u2010 and post\u2010menopausal women (<jats:italic>n<\/jats:italic>\u2009=\u200913) with Group 1\u00a0PAH funded by the National Heart, Lung and Blood Institute. We will determine whether orally administered DHEA 50\u00a0mg daily for 18 weeks affects RV longitudinal strain measured by cardiac magnetic resonance imaging, markers of RV remodeling and oxidative stress, NO and ET\u20101 signaling, sex hormone levels, other PAH intermediate end points, side effects, and safety. The crossover design will elucidate sex\u2010based phenotypes in PAH and whether active treatment with DHEA impacts NO and ET\u20101 biosynthesis. EDIPHY is the first clinical trial of an endogenous sex hormone in PAH. Herein we present the study\u2019s rationale and experimental design.<\/jats:p>","DOI":"10.1177\/2045894021989554","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T03:12:39Z","timestamp":1610680359000},"page":"1-9","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Experimental design of the Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY) trial"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2620-6843","authenticated-orcid":false,"given":"Thomas P.","family":"Walsh","sequence":"first","affiliation":[{"name":"Lifespan Health System Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grayson L.","family":"Baird","sequence":"additional","affiliation":[{"name":"Lifespan Health System Providence RI USA"},{"name":"Department of Diagnostic Imaging Alpert Medical School of Brown University Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3549-2634","authenticated-orcid":false,"given":"Michael K.","family":"Atalay","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging Alpert Medical School of Brown University Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging Alpert Medical School of Brown University Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Arcuri","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging Alpert Medical School of Brown University Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Klinger","sequence":"additional","affiliation":[{"name":"Department of Medicine Alpert Medical School of Brown University Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Mullin","sequence":"additional","affiliation":[{"name":"Department of Medicine Alpert Medical School of Brown University Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Morreo","sequence":"additional","affiliation":[{"name":"Lifespan Health System Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brynn","family":"Normandin","sequence":"additional","affiliation":[{"name":"Lifespan Health System Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sruti","family":"Shiva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology Vascular Medicine Institute NO Metabolomics Core Facility University of Pittsburgh Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Whittenhall","sequence":"additional","affiliation":[{"name":"Department of Medicine Alpert Medical School of Brown University Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey E.","family":"Ventetuolo","sequence":"additional","affiliation":[{"name":"Department of Medicine Alpert Medical School of Brown University Providence RI USA"},{"name":"Department of Health Services Policy and Practice Brown University School of Public Health Providence RI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c190011"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.32.4.730"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(96)70341-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00626.2009"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-118-6-199303150-00006"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(92)90734-D"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70731"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-0404"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-0263"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201509-1785OC"},{"key":"e_1_2_9_12_1","article-title":"Lower DHEA\u2010S levels predict disease and worse outcomes in post\u2010menopausal women with idiopathic, connective tissue disease\u2010 and congenital heart disease\u2010associated pulmonary arterial hypertension","author":"Baird GL","journal-title":"Eur Respir J"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024602"},{"key":"e_1_2_9_14_1","article-title":"Insights from the menstrual cycle in pulmonary arterial hypertension","author":"Baird GL","journal-title":"Ann Am Thorac Soc"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00746.2012"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1633724100"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.848911"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00084503"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802906200"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00301.2013"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00852.x"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.933762"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201410-463OC"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0106"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10615"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2484"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/gme.0b013e31819e8930"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/gme.0b013e31819e8e2d"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0672"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.3.765"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1134"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.12.4650"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.5.1968"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909303411401"},{"key":"e_1_2_9_35_1","first-page":"CD005114","article-title":"Dehydroepiandrosterone for systemic lupus erythematosus","author":"Crosbie D","year":"2007","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20427"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/GME.0000000000000910"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2011.12.005"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01913-2018"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2006.0170"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.08.061"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06-1758"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00100504"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-308365"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-015-0691-z"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-015-1130-4"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00654.2011"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.05.001"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.891077"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603953200"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00310.2004"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506957102"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200702-278OC"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000168414.06853.f0"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.09.030"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201412-572OC"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00127113"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2014.11.294"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.166.1.at1102"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201605-1024OC"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201806-1160ST"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.118.008582"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2018.12.032"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.01.016"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1177\/2045893217748307"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1080\/08916930500285550"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.18.2243"}],"container-title":["Pulmonary Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/2045894021989554","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1177\/2045894021989554","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/2045894021989554","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T05:13:13Z","timestamp":1693199593000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1177\/2045894021989554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":66,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1177\/2045894021989554"],"URL":"https:\/\/doi.org\/10.1177\/2045894021989554","archive":["Portico"],"relation":{},"ISSN":["2045-8940","2045-8940"],"issn-type":[{"value":"2045-8940","type":"print"},{"value":"2045-8940","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4]]}}}