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Hormone replacement therapy may improve pulmonary hypertension and right ventricular function
Last reviewed: 02.07.2025
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Use of hormone replacement therapy (HRT) may be associated with improvements in pulmonary hypertension in women, according to research presented at the American Thoracic Society (ATS) 2024 International Conference, held May 17-22 in San Diego. Pulmonary hypertension (PH) is a type of pulmonary vascular disease that affects the blood vessels between the heart and lungs.
Pulmonary hypertension is classified by the World Symposium on Pulmonary Hypertension (WSPH) into five groups (G1-5PH) based on the suspected cause. The right ventricle of the heart receives blood from the veins of the body and pumps it to the lungs, where it picks up oxygen and gets rid of carbon dioxide.
Study participants had pulmonary hypertension G1, G2, G3, G4, or G5. Although some had mixed disease (eg, both G2 and G3), they were classified by the predominant subtype.
"Our study is unique in that it evaluated more than 700 women at multiple sites across the country to determine the impact of exogenous and endogenous hormonal exposure on pulmonary hypertension," said lead author Audriana Hurbon, MD, assistant professor of medicine at the University of Arizona in Tucson.
For the purposes of this study, endogenous hormones were considered to be those that women's bodies produce before menopause, whereas exogenous hormones were administered through HRT.
Participants were enrolled in the Pulmonary Vascular Disease Phenomics Study (PVDOMICS).
In group 1 pulmonary hypertension (G1PH), women had better preservation of right ventricular function compared with men. However, scientists do not know whether these observations relate to (1) endogenous and exogenous effects of female hormones and (2) non-G1PH types of pulmonary hypertension.
This study examined the associations between endogenous and exogenous hormonal effects on right ventricular function and pulmonary hypertension in women with G1-5PH.
"Although female gender is thought to be associated with preserved right ventricular function in group 1 pulmonary hypertension, the role of estrogen in pulmonary hypertension remains controversial," Dr. Hurbon added.
"In addition, we know that women are more likely to have pulmonary hypertension than men, but when compared, women appear to be less severely ill than men."
The study included 742 women from the G1-5PH groups, the comparison group (those with risk factors for pulmonary hypertension but without the disease itself) and healthy controls from the PVDOMICS study.
Pulmonary vascular disease associated with pulmonary hypertension was defined by mean pulmonary artery pressure on right heart catheterization. Right ventricular function was characterized by shortened right ventricular ejection fraction and right ventricular ejection fraction by echocardiography.
Endogenous hormonal exposure was assessed by self-reported menstrual duration and exogenous exposure by HRT use. Two statistical analyses were performed: one (all pulmonary hypertension groups) and two (by pulmonary hypertension group and exposure) to examine differences in pulmonary vascular disease or right ventricular function.
Results showed that in all pulmonary hypertension groups, mean pulmonary artery pressure decreased with increasing menstrual duration. HRT use was associated with lower mean pulmonary artery pressure and higher right ventricular shortening fraction and right ventricular ejection fraction.
The G1PH group had lower mean pulmonary artery pressure and vascular resistance, and a higher right ventricular ejection fraction when exposed to HRT. The team found no statistically significant differences in the WSPH 2-5 groups.
Although initial analysis showed that longer menstrual periods and HRT were associated with improved pulmonary vascular disease and right ventricular function, further analysis suggested that age and HRT use may have a synergistic effect on improving pulmonary vascular disease.
"This may support the theory that there needs to be a threshold of estrogen exposure for a protective effect," Dr. Hurbon noted.
"We hope that this study will serve as a catalyst for further investigation of the mechanisms of action of female reproductive hormones to identify therapeutic targets for preserving right ventricular function in pulmonary hypertension," the authors concluded.
The results of the study were published in the journal American Thoracic Society.