Can hormone replacement therapy help treat pulmonary hypertension in women?

• About 1% of the global population has pulmonary hypertension, which currently has no cure.
• The condition is more common in females, and scientists believe it may be due to the hormone estrogen.
• Researchers from The University of Arizona College of Medicine Tucson say that hormone replacement therapy (HRT) may improve pulmonary hypertension in females.

Researchers estimate that about 1% of the global population has pulmonary hypertension — a disease caused by high blood pressure in the blood vessels that deliver oxygen to the lungs.

Past studies show that pulmonary hypertension is more common in females , for which there is currently no cure.

Scientists believe the hormone estrogen may play an important role in pulmonary hypertension in females.

Now, researchers from The University of Arizona College of Medicine Tucson report during a presentation at the American Thoracic Society 2024 International Conference that hormone replacement therapy (HRT) may improve pulmonary hypertension symptoms in females. The findings have not yet been published in a peer-reviewed scientific journal.

Studying different types of pulmonary hypertension

For this study, researchers recruited a total of 742 female participants. Those who had pulmonary hypertension were classified into the five groups established by the World Symposium on Pulmonary Hypertension :

• Group 1: Pulmonary arterial hypertension
• Group 2: Pulmonary hypertension caused by left heart disease
• Group 3: Pulmonary hypertension caused by lung disease
• Group 4: Pulmonary hypertension from chronic blood clots in the lungs
• Group 5: Pulmonary hypertension from unknown cause

“Pulmonary hypertension is a progressive disease that can significantly impact one’s quality [of life] despite current treatments,” Audriana Hurbon, MD , assistant clinical professor in the Department of Medicine at The University of Arizona College of Medicine Tucson and corresponding author of this study told Medical News Today .

“Because we know that in Group 1 pulmonary hypertension women can be affected more often than men, we also know that once affected we have observed less severe disease than (men). We wanted to explore a suspected hormonal contribution to this observation.”

Other female participants included those with risk factors for pulmonary hypertension but who did not have this disease and healthy controls.

Pulmonary hypertension severity linked to duration of menses

Researchers examined the impact of both exogenous and endogenous hormone exposure on pulmonary hypertension.

“Because we wanted to explore the suspected hormonal impact, endogenous hormone exposure was defined as one’s lifetime duration of menses , and exogenous hormone exposure was defined as one ever having used hormone replacement therapy (HRT),” Hurbon explained.

Upon analysis, Hurbon and her team discovered that average pulmonary arterial pressure decreased with a greater lifetime duration of menstruation across all pulmonary hypertension groups.

“We wanted to assess whether there was a difference between pulmonary vascular disease — where we looked at pulmonary arterial pressure and pulmonary vascular resistance , which was measured by right heart catheterization — and also right ventricular function — defined by measurement of right ventricular fractional shortening from echocardiography and right ventricular ejection fraction from cardiac MRI — between those who had greater lifetime duration of menses and use of HRT,” Hurbon said.

“Ultimately there was no statistically significant difference with lifetime duration of menses in regard to pulmonary vascular disease, but we did observe improvement with right ventricular ejection fraction.”

H RT improves pulmonary hypertension symptoms

Researchers found an association between the use of hormone replacement therapy and lower mean pulmonary artery pressure, higher right ventricular fractional shortening, and right ventricular ejection fraction.

“ So far, our preliminary data has been positive with improvement (in) mean pulmonary arterial pressure, pulmonary vascular resistance, right ventricular ejection fraction, and right ventricular fractional shortening with the use of HRT in the pulmonary hypertension cohort,” Hurbon said.

“We didn’t observe a difference with the healthy controls or comparator — one with risk factors for pulmonary hypertension but does not have the disease — with increased lifetime duration of menses or with use of HRT. These findings were consistent with our hypothesis that suggests that hormones could be protective with this pulmonary hypertension subgroup.”

Additionally, those in the pulmonary hypertension Group 1 had lower mean pulmonary artery pressure, pulmonary vascular resistance, and higher right ventricular ejection fraction if exposed to HRT.

“Additional studies are needed to further explore this,” Hurbon said. “Preliminary data suggests that these findings are most notable with Group 1 pulmonary hypertension compared to the other subgroups of pulmonary hypertension.”

HRT linked to adverse cardiac events

After reviewing this study, Nicole Weinberg, MD , a board certified cardiologist at Providence Saint John’s Health Center in Santa Monica, CA, told MNT the findings may cause controversy, noting the following:

“We know that hormones do have some pros and cons , and it’s something that I feel we’ve struggled with in the world of preventative health — for every positive study, there’s a negative study,” Weinberg continued. “I think hormones, for one thing, are vasodilating medications — they can cause your blood vessels to plump. So if you think about a disease process like pulmonary hypertension, that is a facet of the drugs that we use for pulmonary hypertension, that can be very beneficial to cause more blood flow due to the circulation that’s being compromised.”

“The flip side of it is the induction of actual hormones can cause increased clotting risks and things like that, that we already worry about quite significantly in this group of patients,” Weinberg continued. “So it’ll be interesting to see when they flesh out further research data where this ends up.”

There is also controversy regarding the use of HRT and the cardiovascular system.

While some studies say that HRT may help protect the body from cardiovascular disease, other studies say differently, such as a recent study reported that HRT may not help prevent heart disease .

More research on estrogen and pulmonary hypertension needed

MNT also spoke with Cheng-Han Chen, MD , a board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, about this study.

As public hypertension is a notoriously difficult condition to treat, Chen said this study provides a useful new avenue of research into new approaches for this condition.

“These findings will not affect how we approach hormone replacement therapy simply because it’s too early of a stage of research,” he continued. “Right now the decision to start therapies will still be rather individualized and mostly revolve around patients with severe menopausal symptoms that affect their quality of life.”

“ Future research should focus on confirming this relationship between estrogen and improving pulmonary hypertension, preferably with randomized control trials,” Chen noted.