The main purpose of this clinical trial is to examine the feasibility and effects of fulvestrant in post-menopausal women with pulmonary arterial hypertension (PAH). The study will evaluate how well the drug is tolerated. The study will evaluate changes in circulating hematopoietic progenitor cells, plasma hormone levels, NT-proBNP, and other plasma biomarkers after the administration of fulvestrant. Changes in tricuspid annular plane systolic excursion, stroke volume index, right ventricular fractional area change, and other echo parameters after fulvestrant administration will be evaluated as well as changes in distance walked in six minutes.

Inclusion Criteria:

• Previous documentation of mean pulmonary artery pressure > 25 mm Hg with a pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) < 16 mm Hg and pulmonary vascular resistance > 3 WU at any time before study entry.
• Diagnosis of PAH which is idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease, congenital heart disease, portal hypertension, or HIV infection.
• Most recent pulmonary function tests with FEV1/FVC >50% AND either a) total lung capacity > 70% predicted or b) total lung capacity between 60% and 70% predicted with no more than mild interstitial lung disease on computerized tomography scan of the chest.
• Female, post-menopausal state, defined as:
• > 50 years old and a) have not menstruated during the preceding 12 months or b) have follicle-stimulating hormone (FSH) levels > 40 IU/L or
• < 50 years and FSH > 40 IU/L or
• having had a bilateral oophorectomy.
• Informed consent.

Exclusion Criteria:

• Age < 18.
• Treatment with estrogen or anti-hormone therapy (tamoxifen, anastrozole, etc.)
• WHO Class IV functional status.
• History of breast cancer.
• Clinically significant untreated sleep apnea.
• Left-sided valvular disease (more than moderate mitral valve stenosis or insufficiency or aortic stenosis or insufficiency), pulmonary artery or valve stenosis, or ejection fraction < 45% on echocardiography.
• Initiation of PAH therapy (prostacyclin analogues or receptor agonists, endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators) within three months of enrollment; the dose must be stable for at least 3 months prior to Baseline Visit. PAH therapy which is stopped and then restarted or has dose changes which are not related to initiation and uptitration will be allowed within 3 months prior to the Baseline Visit.
• Hormone therapy.
• Use of warfarin or other anticoagulant (use of aspirin is permitted).
• Platelet count <100,000.
• Renal failure (creatinine >/= 2.0).
• Child-Pugh Class C cirrhosis.
• Current or recent (< 6 months) chronic heavy alcohol consumption.
• Current use of another investigational drug (non-FDA approved) for PAH.

12 weeks

Small size Open-label and uncontrolled design, making it difficult to directly attribute the findings to the study intervention Short duration of the study may have affected the results