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Published on: May 11, 2015
Effects of Dehydroepiandrosterone in Pulmonary Hypertension (EDIPHY): A Randomized, Double-Blind, Placebo-Controlled
Rachel Sanders1, Thomas Walsh2, Grayson L Baird1,3
1Brown University Health, Providence, RI.
Rationale:
Low levels of dehydroepiandrosterone (DHEA) and its sulfated form (DHEA-S) occur in pulmonary arterial hypertension (PAH) and are associated with worse right ventricular (RV) function.
Objectives:
We sought to determine whether DHEA improved RV function measured by cardiac magnetic resonance imaging in PAH.
Methods:
We conducted a randomized, double-blind, placebo-controlled crossover trial of DHEA in PAH participants. The primary outcome was change in RV longitudinal strain after 18 weeks.
Measurements And Main Results:
Twenty-six participants were randomized to DHEA first or placebo first, 20 (77%) were female. 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] vs. 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. DHEA may have worsened RV circumferential strain as compared to placebo (p = 0.05, both treatment periods). Active treatment with DHEA significantly increased serum DHEA-S levels (p < 0.0001); higher DHEA-S levels were associated with improved PAH metrics. Active treatment with DHEA significantly increased serum testosterone levels (p < 0.01, both treatment periods). There was no difference in adverse events.
Conclusions:
DHEA treatment did not improve RV longitudinal strain in this crossover trial but had variable and possibly beneficial effects on other PAH endpoints. DHEA was safe and well tolerated. DHEA increased DHEA-S and testosterone levels, which may explain the discordant results.Clinical trial registered with www.clinicaltrials.gov (NCT03648385).
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