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Review
. 2024 Apr;181(7):938-966.
doi: 10.1111/bph.16277. Epub 2024 Jan 16.

Pulmonary arterial hypertension: Sex matters

Joshua P Dignam  1 , Smriti Sharma  1 , Ioannis Stasinopoulos  1   2 , Margaret R MacLean  1
Affiliations
Free article
Review

Pulmonary arterial hypertension: Sex matters

Joshua P Dignam et al. Br J Pharmacol. 2024 Apr.
Free article

Abstract

Pulmonary arterial hypertension (PAH) is a complex disease of multifactorial origin. While registries have demonstrated that women are more susceptible to the disease, females with PAH have superior right ventricle (RV) function and a better prognosis than their male counterparts, a phenomenon referred to as the 'estrogen paradox'. Numerous pre-clinical studies have investigated the involvement of sex hormones in PAH pathobiology, often with conflicting results. However, recent advances suggest that abnormal estrogen synthesis, metabolism and signalling underpin the sexual dimorphism of this disease. Other sex hormones, such as progesterone, testosterone and dehydroepiandrosterone may also play a role. Several non-hormonal factor including sex chromosomes and epigenetics have also been implicated. Though the underlying pathophysiological mechanisms are complex, several compounds that modulate sex hormones levels and signalling are under investigation in PAH patients. Further elucidation of the estrogen paradox will set the stage for the identification of additional therapeutic targets for this disease.

Keywords: estrogen; pulmonary hypertension; right ventricle; sex chromosomes; sex hormones.

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Conflict of interest statement

The authors declare no conflict of interest.

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