Pulmonary Hypertension and Anastrozole Trial

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
PVR > 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 and receiving treatment for PAH.

- 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.

- Ability to perform six minute walk testing without significant limitations in
musculoskeletal function or coordination.

- If 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.

- Current treatment with estrogen, hormone therapy, or anti-hormone therapy (tamoxifen,
fulvestrant, etc.)

- WHO Class IV functional status.

- History of invasive 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 most recent echocardiography (within 1 year).

- Initiation of PAH therapy (prostacyclin analogues, endothelin-1 receptor antagonists,
phosphodiesterase-5 inhibitors, riociguat, selexipag) within three months of
enrollment; the dose must be stable for at least three 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.

- Hospitalized or acutely ill.

- Renal failure (creatinine ≥ 2.0).

- Hypercalcemia.

- Severe osteoporosis: T score -2.5 to -3.4 without bone modifying treatment OR T score
= - 3.5 or lower

- Child-Pugh Class C cirrhosis.

- Current or recent (< 3 months) chronic heavy alcohol consumption.

- Enrollment in a clinical trial or concurrent use of another investigational drug or
device within 30 days of screening visit.