Gender, sex hormones and pulmonary hypertension

Eric D. Austin, Tim Lahm, James West, Stevan P. Tofovic, Anne Katrine Johansen, Margaret R. MacLean, Abdallah Alzoubi, Masahiko Oka

Research output: Contribution to journalReview article

56 Scopus citations

Abstract

Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a greater susceptibility to disease among females, although females with PAH appear to live longer after diagnosis. While this “estrogen paradox” of enhanced female survival despite increased female susceptibility remains a mystery, recent progress has begun to shed light upon the interplay of sex hormones, the pathogenesis of pulmonary hypertension, and the right ventricular response to stress. For example, emerging data in humans and experimental models suggest that estrogens or differential sex hormone metabolism may modify disease risk among susceptible subjects, and that estrogens may interact with additional local factors such as serotonin to enhance the potentially damaging chronic effects of estrogens on the pulmonary vasculature. Regardless, it remains unclear why not all estrogenic compounds behave equally, nor why estrogens appear to be protective in certain settings but detrimental in others. The contribution of androgens and other compounds, such as dehydroepiandrosterone, to pathogenesis and possibly treatment must be considered as well. In this review, we will discuss the recent understandings on how estrogens, estrogen metabolism, dehydroepiandrosterone, and additional susceptibility factors may all contribute to the pathogenesis or potentially to the treatment of pulmonary hypertension, by evaluating current human, cell-based, and experimental model data.

Original languageEnglish (US)
Pages (from-to)294-314
Number of pages21
JournalPulmonary Circulation
Volume3
Issue number2
DOIs
StatePublished - Apr 2013

Keywords

  • Bone morphogenetic protein receptor type II
  • Dehydroepiandrosterone
  • Estrogen
  • Pulmonary hypertension
  • Serotonin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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  • Cite this

    Austin, E. D., Lahm, T., West, J., Tofovic, S. P., Johansen, A. K., MacLean, M. R., Alzoubi, A., & Oka, M. (2013). Gender, sex hormones and pulmonary hypertension. Pulmonary Circulation, 3(2), 294-314. https://doi.org/10.4103/2045-8932.114756