Pulmonary arterial hypertension (PAH) in all its forms is often associated with progression to right heart failure. Several types of PAH occur more frequently in women than men. Since studies suggested that greater estrogen production may have been linked to PAH, a group of researchers sought to find out if anastrozole (AN) (Arimidex®), a breast cancer treatment that affects estrogen production and has been shown to reduce pulmonary hypertension (PH) in animals, could be effective in patients with PAH. (https://www.ncbi.nlm.nih.gov/pubmed/27602993) Although AN has been approved for use in breast cancer for 20 years, it’s unclear if the medication could diminish estrogen levels and improve right ventricular function.

Steven M. Kawut, MD, MS, at the Perelman School of Medicine at the University of Pennsylvania, led a team of physician researchers in what they submit is the “first randomized clinical trial of a therapy targeting sex hormones in PAH.”

Eighteen patients, men and post-menopausal women over the age of 18 from pulmonary vascular disease clinics at the University of Pennsylvania and Rhode Island Hospital/Brown University, participated in the randomized, double-blind, placebo-controlled study, which took place between January 2013 and January 2015. The subjects were randomly divided into two groups; one group of 12 subjects received anastrozole 1 mg and the control group of six subjects received an inactive substance (e.g., placebo).

Study participants were analyzed after six weeks and three months on either anastrazole or placebo, and estrogen levels had decreased by 40 percent in the AN group; there was no change in the placebo group. There was no difference in right ventricular function between the group receiving AN and the placebo group. However, the six-minute walk distance (6MWD) increased 26 meters in the group taking AN; the placebo group had a decrease in 6MWD of 12 meters. The authors reported no differences in side effects or serious adverse events between the groups. Health-related quality of life (HRQoL) remained the same and the authors found no differences between the two groups in inflammation or development of blood clots.

Dr. Kawut indicated that studies have found women without clinical cardiovascular disease and those with PAH have better RV function than men; women also have better survival rates compared to men. It is difficult to explain the greater risk of PAH in women, while they seem to have better outcomes than men. This study showed that AN reduced estradiol by 40 percent; however, postmenopausal women with breast cancer who received AN experienced a greater reduction in estrogen levels, according to Dr. Kawut.

Although the results are promising, the authors emphasized that a study of this size and scope – only 18 subjects studied over three months – is not definitive and does not reveal the long-term effects of AN on PAH. They suggested that larger studies of greater duration should be conducted to produce more significant findings on the use of AN on patients with PAH.

Steven Kawut, MD, MS, Professor of Medicine and Epidemiology at the Perelman School of Medicine at the University of Pennsylvania, is Director of the Pulmonary Hypertension/Pulmonary Vascular Disease Program at Penn Medicine. He also serves on the Pulmonary Hypertension Association (PHA)’s Scientific Leadership Council and as Chair of PHA’s PH Care Centers Registry Task Force.