Hormone replacement therapy may improve pulmonary hypertension and right ventricular function

Use of hormone replacement therapy (HRT) may be associated with improvements in pulmonary hypertension in women, according to a study presented at the American Thoracic Society (ATS) 2024 International Conference, May 17 to 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) depending on the suspected cause. The right ventricle of the heart receives blood from the veins of the body and sends it to the lungs, where it is saturated with oxygen and gets rid of carbon dioxide.

Study participants had G1, G2, G3, G4, or G5 pulmonary hypertension. Although some had mixed disease (eg, both G2 and G3), they were classified according to their predominant subtype.

“Our study is unique in that it evaluated more than 700 women at multiple sites across the country to determine the effects of exogenous and endogenous hormonal exposure on pulmonary hypertension,” said lead author Audriana Hurbon, MD, assistant professor of medicine. 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, while exogenous hormones were administered through HRT.

Study 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 apply to (1) endogenous and exogenous exposure to 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 sex is thought to be associated with preserved right ventricular function in group 1 pulmonary hypertension, the role of estrogen in pulmonary hypertension remains controversial,” added Dr. Hurbon.

“Additionally, 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 groups G1-5PH, a comparison group (those with risk factors for pulmonary hypertension but not the disease itself), and healthy controls from the PVDOMICS study.

Pulmonary vascular disease associated with pulmonary hypertension was determined by mean pulmonary artery pressure during right heart catheterization. Right ventricular function was characterized by shortening of the right ventricular fraction and right ventricular ejection fraction according to echocardiography.

Endogenous hormonal exposure was assessed by the duration of self-reported menstrual periods, and exogenous exposure was assessed by the use of HRT. Two statistical analyzes were performed: one (all pulmonary hypertension groups) and two-way (by pulmonary hypertension group and exposure) to examine differences in pulmonary vascular disease or right ventricular function.

The 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, as well as 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 found that longer periods and HRT were associated with improvements in pulmonary vascular disease and right ventricular function, further analysis suggested that age and HRT use may have a synergistic effect in improving pulmonary vascular disease.

“This may support the theory that there is a necessary threshold of estrogen exposure for a protective effect,” Dr. Hurbon noted.

“We hope that this study will serve as a catalyst for further exploration 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 study results were published in the journal of the American Thoracic Society.