Yes, exemestane is an aromatase inhibitor, and a specific type at that. It belongs to the steroidal, irreversible class of aromatase inhibitors, which makes it structurally and mechanically different from the other two commonly prescribed drugs in this category, letrozole and anastrozole. All three are used to treat hormone-receptor-positive breast cancer in postmenopausal women, but exemestane works in a distinct way that’s worth understanding.
How Exemestane Blocks Estrogen Production
Aromatase is the enzyme responsible for converting androgens into estrogen. In postmenopausal women, this conversion is the body’s primary remaining source of estrogen. Because certain breast cancers rely on estrogen to grow, shutting down this enzyme starves the tumor of its fuel.
Exemestane works by binding permanently to the aromatase enzyme and destroying it. Once exemestane attaches, that copy of the enzyme is done for good. The body has to manufacture entirely new aromatase molecules to resume estrogen production. This is why exemestane is classified as an irreversible (sometimes called “suicidal”) inhibitor. Both classes of aromatase inhibitor suppress estrogen to levels so low they’re essentially undetectable on standard lab tests, but they get there by different routes.
Steroidal vs. Non-Steroidal Aromatase Inhibitors
The three third-generation aromatase inhibitors prescribed today fall into two camps. Letrozole and anastrozole are non-steroidal agents. They bind to aromatase reversibly, meaning the bond can eventually release. Exemestane is a steroid-based molecule that binds irreversibly. In practice, all three are potent enough to drive estrogen to near-zero levels. Whether the pharmacological difference between irreversible and reversible binding translates into meaningful clinical differences for patients remains an open question, with limited head-to-head data comparing the three drugs directly.
One practical implication of the structural difference: because exemestane is a steroid and the others are not, a patient who develops intolerable side effects on one type may sometimes be switched to the other type. The different chemical structure can occasionally produce a different side effect profile for an individual patient.
What Exemestane Is Prescribed For
Exemestane (sold under the brand name Aromasin) has two FDA-approved uses. The first is adjuvant treatment of postmenopausal women with estrogen-receptor-positive early breast cancer who have already taken tamoxifen for two to three years. In this setting, exemestane replaces tamoxifen for the remainder of a total five-year course of hormonal therapy. The second indication is for advanced breast cancer in postmenopausal women whose disease has progressed on tamoxifen.
In the large trial that established its role as a follow-on to tamoxifen, women who switched to exemestane had a 19 percent lower risk of breast cancer recurrence compared to those who stayed on tamoxifen alone. They also had a 16 percent lower risk of distant recurrence, meaning cancer spreading to other parts of the body. These results, published by the National Cancer Institute, helped cement the sequential tamoxifen-to-exemestane approach as a standard treatment strategy.
Common Side Effects
Because exemestane works by depleting estrogen, most of its side effects are related to very low estrogen levels. In the early breast cancer trial comparing exemestane to tamoxifen, the most frequently reported side effects in the exemestane group were:
- Hot flushes: 21% of patients
- Joint pain: 15%
- Headache: 13%
- Insomnia: 12%
- Increased sweating: 12%
Joint pain is a particularly notable side effect across all aromatase inhibitors. It affects a meaningful number of patients and is one of the more common reasons women find the medication difficult to tolerate. In the same trial, about 6% of women on exemestane discontinued treatment due to side effects, a rate similar to the 5% seen with tamoxifen.
Bone Health and Other Risks
Estrogen plays a protective role in maintaining bone density, so suppressing it to very low levels raises the risk of bone thinning. In clinical trials, fractures occurred in 4.2% of women taking exemestane compared to 3.1% on tamoxifen. This is a modest but real increase, and women on any aromatase inhibitor are typically monitored with periodic bone density scans.
Cardiac events were also tracked in trials. Ischemic heart events (such as angina or heart attack) occurred in 1.6% of the exemestane group versus 0.6% on tamoxifen. Heart failure rates were similar between the two groups at under half a percent. Carpal tunnel syndrome, though uncommon overall, was more frequent with exemestane (2.4%) than tamoxifen (0.2%).
How It’s Taken
The standard dose is one 25 mg tablet taken once daily after a meal. Food increases the absorption of exemestane, so taking it on an empty stomach reduces how much of the drug your body actually uses. For advanced breast cancer, treatment continues as long as the cancer isn’t progressing. In the adjuvant (preventive) setting, it’s typically taken for the remaining years of a five-year hormonal therapy plan after an initial period on tamoxifen.