The main purpose of this clinical trial is to study the safety and efficacy of anastrozole in adults diagnosed with pulmonary arterial hypertension (PAH). The study will evaluate how well the drug is tolerated. The study will also evaluate if anastrozole effects estradiol (E2) hormone levels, a sex hormone, and improves the function of the lower right chamber of the heart (right ventricle).

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.
• 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 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:

• Treatment with estrogen or anti-hormone therapy (tamoxifen, fulvestrant, 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, endothelin-1 receptor antagonists, phosphodiesterase-5 inhibitors) within three months of enrollment; the dose must be stable for at least 3 months prior to Baseline Visit
• Hormone therapy
• Hospitalized or acutely ill
• 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
• Enrollment in a clinical trial within one month of screening
• Age < 18

Adverse event data collected from Screening through 3 months

• Small sample size
• No changes in echo parameters
• Unclear mechanism for impact on 6MWD