Estrogen Receptor Antagonist in Patients With Pulmonary Arterial Hypertension

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.