{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T11:30:18Z","timestamp":1782300618642,"version":"3.54.5"},"posted":{"date-parts":[[2025,8,3]]},"group-title":"Cardiovascular Medicine","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Rationale<\/jats:title>\n                  <jats:p>The adrenal steroid dehydroepiandrosterone (DHEA) and its sulfated form (DHEA-S) are deficient in pulmonary arterial hypertension (PAH) and lower levels are associated with worse right ventricular (RV) function, a decisive factor for survival in PAH.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We sought to determine whether DHEA improved RV function as measured by cardiac magnetic resonance imaging (MRI) in PAH.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a randomized, double-blind, placebo-controlled crossover clinical trial of DHEA in participants with PAH at a single center. All participants and study staff were blinded. The primary outcome was change in RV longitudinal strain as measured by MRI after 18 weeks. Key secondary outcomes were the change in serum DHEA-S levels and other PAH end points after 18 weeks.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Measurements and Main Results<\/jats:title>\n                  <jats:p>A total of 26 participants were randomized to DHEA first or placebo first between 2019 and 2024, 20 (77%) of whom were females. Twenty- three (88%) participants completed the study; one participant completely withdrew. DHEA had no effect on RV longitudinal strain. DHEA improved RV short axis radial strain (20.7% [95% CI 16.7, 24.6] to 23.1% [95% CI 19.5, 26.7] compared to placebo (21.1% [95% CI 18.1, 24.0] to 19.3% [95% CI 16.5, 22.2])(p = 0.031), as well as emPHasis-10 scores (p = 0.037) and Short Form-36 physical component scores (p = 0.044) in the second treatment period. In both treatment periods, DHEA may have worsened RV circumferential strain as compared to placebo (p = 0.047, p = 0.052 respectively). Active treatment with DHEA significantly increased serum DHEA-S levels at the end of both treatment periods (p&lt;0.0001), which was in turn associated with multiple study end points in the predicted direction (higher DHEA-S levels, improved PAH metrics). Active treatment with DHEA significantly increased serum testosterone levels as compared to placebo (p &lt;0.01 for both treatment periods), which may have counteracted effects of DHEA supplementation. There was no difference in adverse events.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>DHEA treatment did not improve RV longitudinal strain in this pilot crossover trial but had variable and possibly beneficial effects on other PAH endpoints. DHEA increased DHEA-S and testosterone levels, which may explain some of the discordant results. DHEA is safe and well tolerated in PAH.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Clinical trial registered with<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link>\n                    <jats:bold>\n                      (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03648385\">NCT03648385<\/jats:ext-link>\n                      )\n                    <\/jats:bold>\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.01.25332627","type":"posted-content","created":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T18:50:11Z","timestamp":1754247011000},"source":"Crossref","is-referenced-by-count":5,"title":["Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY): A Randomized, Double-Blind, Placebo-Controlled Crossover Trial"],"prefix":"10.64898","author":[{"given":"Rachel","family":"Sanders","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grayson L.","family":"Baird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Atalay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Arcuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2997-5955","authenticated-orcid":false,"given":"James R.","family":"Klinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Mullin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7315-5535","authenticated-orcid":false,"given":"James","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8058-3004","authenticated-orcid":false,"given":"Navneet","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Whittenhall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4223-4775","authenticated-orcid":false,"given":"Corey E.","family":"Ventetuolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025080522102030000_2025.08.01.25332627v1.1","doi-asserted-by":"crossref","unstructured":"Ventetuolo CE , Baird GL , Barr RG , Bluemke DA , Fritz JS , Hill NS , Klinger JR , Lima JA , Ouyang P , Palevsky HI , Palmisciano AJ , Krishnan I , Pinder D , Preston IR , Roberts KE , Kawut SM . 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