Use of hormone replacement therapy (HRT) may be associated with improved pulmonary hypertension in women, according to research presented at the ATS International Conference 2024. Pulmonary hypertension (PH) is a type of pulmonary vascular disease—a disease that affects the blood vessels along the path between the heart and the lungs.
Pulmonary hypertension is classified by the World Symposium on Pulmonary Hypertension (WSPH) into five groups (G1-5PH) based on its suspected cause. The right ventricle of the heart receives blood from the body’s veins and pushes it to the lungs, where it is oxygenated and carbon dioxide is removed.
Study participants had G1, G2, G3, G4 or G5 pulmonary hypertension. While some had mixed disease (for example, both G2 and G3), they were categorized by the predominant subtype.
Our study is unique in that it evaluated more than 700 women at multiple institutions nationwide to help determine the effect of exposure to exogenous and endogenous hormones on pulmonary hypertension.”
Audriana Hurbon, MD, corresponding author, assistant clinical professor, medicine, Department of Medicine, University of Arizona College of Medicine, Tucson
For the purposes of this study, endogenous hormones were considered those produced by women’s bodies before menopause, while exogenous hormones were introduced through HRT.
Research participants were enrolled in the PVDOMICS (Pulmonary Vascular Disease Phenomics) study sponsored by the National Heart Lung and Blood Institute.
In WSPH Group 1 pulmonary hypertension (G1PH), being female has been associated with better preservation of right ventricular function than men. However, scientists do not know whether these observations, (1) apply to both endogenous and exogenous female hormone exposure, and (2) apply to types of pulmonary hypertension other than G1PH. This study investigated the relationships between endogenous and exogenous hormone exposure on right ventricular function and pulmonary hypertension among women with G1-5PH.
“While it is accepted that in Pulmonary Hypertension World Symposium Group 1 female gender is associated with preservation of right ventricular function, the role of estrogen in pulmonary hypertension has been controversial,” added Dr. Hurbon. “Furthermore, we know that women are affected by pulmonary hypertension more often than men, but when compared to each other, women appear to be less severely affected than men.”
The study included 742 women from G1-5PH, comparators (those with risk factors for pulmonary hypertension but without this disease) and healthy controls enrolled in 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 right ventricular shortening fraction and right ventricular ejection fraction by echocardiography.
Endogenous hormone exposure was quantified by self-reported menstrual lifetime duration and exogenous exposure by taking HRT. Two statistical analyzes were performed: One (all pulmonary hypertension groups) and two-way (by both pulmonary hypertension group and exposure) to examine differences in pulmonary vascular disease or right ventricular function.
The results: In all pulmonary hypertension groups, mean pulmonary arterial pressure decreased with longer menstrual life. HRT use was associated with lower mean pulmonary artery pressure and higher right ventricular fractional shortening and right ventricular ejection fraction. G1PH had lower mean pulmonary artery pressure and pulmonary vascular resistance and higher right ventricular ejection fraction with exposure to hormone replacement therapy. The team found no statistical differences in WSPH Groups 2-5.
While the panel’s initial analysis showed that longer menarcheal lifespan and HRT were associated with improved pulmonary vascular disease and right ventricular function associated with pulmonary hypertension, further analysis has suggested that age in addition to HRT use may to have a synergistic effect on the pulmonary vessels. improvement of the disease. “This could support a theory that suggests a threshold of estrogen exposure is necessary for a protective effect,” noted Dr. Herbon.
“We hope that this study will be a catalyst for further investigation of female reproductive hormone mechanisms to identify therapeutic targets for right ventricular preservation in pulmonary hypertension,” the authors concluded.
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