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. 2016 May 15;193(10):1168-75.
doi: 10.1164/rccm.201509-1785OC.

Higher Estradiol and Lower Dehydroepiandrosterone-Sulfate Levels Are Associated with Pulmonary Arterial Hypertension in Men

Corey E Ventetuolo  1   2   3 , Grayson L Baird  3 , R Graham Barr  4 , David A Bluemke  5 , Jason S Fritz  6 , Nicholas S Hill  7 , James R Klinger  1   3 , Joao A C Lima  8 , Pamela Ouyang  8 , Harold I Palevsky  6 , Amy J Palmisciano  3 , Ipsita Krishnan  3 , Diane Pinder  6 , Ioana R Preston  7 , Kari E Roberts  7 , Steven M Kawut  6   9   10
Affiliations

Higher Estradiol and Lower Dehydroepiandrosterone-Sulfate Levels Are Associated with Pulmonary Arterial Hypertension in Men

Corey E Ventetuolo et al. Am J Respir Crit Care Med. .

Abstract

Rationale: Recent studies have focused on the role of female sex and estradiol (E2) in pulmonary arterial hypertension (PAH), but it is not known whether sex hormones are risk factors for PAH in men.

Objectives: We performed a case-control study to determine whether hormone levels (E2, dehydroepiandrosterone-sulfate [DHEA-S], and testosterone) are associated with PAH in men.

Methods: Plasma sex hormone levels in men with idiopathic, heritable, or connective tissue disease-associated PAH were compared with those from age- and body mass index-matched men without clinical cardiovascular disease.

Measurements and main results: There were 23 cases with PAH (70% had idiopathic PAH, 65% were functional class III/IV) and 67 control subjects. Higher E2 and E2/testosterone levels were associated with the risk of PAH (odds ratio per 1 ln[E2:testosterone], 6.0; 95% confidence interval, 2.2-16.4; P = 0.001), whereas higher levels of DHEA-S were associated with a reduced risk (odds ratio per 1 ln[DHEA-S], 0.1; 95% confidence interval, 0.0-0.3; P = 0.001). E2 and DHEA-S levels were strong predictors of case status (C statistic for both, 0.82) but testosterone was not (C statistic, 0.53). Higher levels of E2 were associated with shorter 6-minute-walk distances (P = 0.03), whereas higher levels of DHEA-S were associated with lower right atrial pressure (P = 0.02) and pulmonary vascular resistance (P = 0.01) in men with PAH.

Conclusions: Higher levels of E2 and lower levels of DHEA-S were associated with PAH in men. Sex-based differences in sex hormone processing and signaling may contribute to unique phenotypes in pulmonary vascular disease.

Keywords: DHEA; estradiol; pulmonary hypertension; sex hormones.

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Figures

Figure 1.
Figure 1.
Sex hormone levels by case/control status adjusted for age and body mass index (as continuous measures). Interquartile range (box) and outlying values (whiskers) are shown. Estradiol (A), dehydroepiandrosterone-sulfate (DHEA-S) (B), total testosterone (C), and bioavailable testosterone (D).
Figure 2.
Figure 2.
Receiver operating characteristic curves of total testosterone (Total T) (solid blue line), estradiol (E2) (dashed red line), and dehydroepiandrosterone-sulfate (DHEA-S) (dashed green line) for case status.
See this image and copyright information in PMC

Comment in

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