Short answer: Both block aromatase, the enzyme that makes estrogen. Anastrozole (Arimidex) is a nonsteroidal blocker; exemestane (Aromasin) is a steroid that binds the enzyme permanently.12 Both are approved for breast cancer in postmenopausal women. In the MA.27 trial of 7,576 women, breast cancer outcomes were the same.3 Use in men is off label.
| Anastrozole (Arimidex) | Exemestane (Aromasin) | |
|---|---|---|
| Mechanism | Selective nonsteroidal aromatase inhibitor1 | Irreversible steroidal aromatase inactivator ("suicide inhibition"), related to androstenedione2 |
| Approval status | FDA approved for hormone receptor-positive breast cancer in postmenopausal women1 | FDA approved for ER-positive breast cancer in postmenopausal women, after tamoxifen2 |
| Label dosing schedule | 1 mg once daily, with or without food1 | 25 mg once daily after a meal; 50 mg with strong CYP3A4 inducers2 |
| Half-life | about 2 days (label: mean 50 hours)1 | about 24 hours (label: mean terminal half-life about 24 hours)2 |
| Time to peak (Tmax) | about 2 hours fasted; delayed to about 5 hours after food1 | about 2 hours (label: 1.2 hours in women with breast cancer, 2.9 hours in healthy women)2 |
| Food effect | Food slows absorption but not the total amount1 | High-fat breakfast raised exposure (AUC) by 59%2 |
| Estrogen lowering | About 70% within 24 hours and 80% after 14 days of 1 mg daily1 | At least 85% to 95% at 25 mg daily2 |
| Androgen activity | No direct androgenic activity in animals1 | A metabolite binds the androgen receptor about 100 times more than exemestane itself2 |
| Notable label warnings | Bone density loss; raised cholesterol (9% vs 3.5% on tamoxifen in ATAC)1 | Bone density loss; HDL cholesterol fell 6% to 9% in one study2 |
Anastrozole sits in the aromatase enzyme and blocks it while the drug is present.1 Exemestane looks like the enzyme's natural fuel, androstenedione. The enzyme processes it into a form that binds permanently and switches that enzyme copy off.2 After one 25 mg dose of exemestane, estrogen suppression peaked at 2 to 3 days and lasted 4 to 5 days.2 With anastrozole, suppression lasted up to 6 days after stopping daily dosing.1
Yes, in breast cancer. MA.27 randomized 7,576 postmenopausal women to 5 years of exemestane or anastrozole. At a median of 4.1 years, event-free survival was 91% vs 91.2%, with no difference. Osteoporosis or osteopenia, high triglycerides and high cholesterol were less common on exemestane; mild liver test changes and rare atrial fibrillation were less common on anastrozole.3 There is no comparable head-to-head trial in men.
Neither label covers men. Studies in men exist but are small. In older men with low or borderline testosterone, anastrozole raised testosterone and lowered estradiol over 12 weeks4, and over 1 year it lowered spine bone density compared with placebo.5 A 10-day study in 12 healthy young men found exemestane lowered estradiol by about a third and raised testosterone by about 60%.6 In adolescent boys with pubertal gynecomastia, anastrozole did no better than placebo, per the Arimidex label.1 Any use in men is a decision for a prescriber, with blood work.