Does Exemestane Contain Steroids?
Yes, exemestane is itself a steroidal compound—specifically, a steroidal aromatase inhibitor with a chemical structure derived from androstenedione. 1, 2
Chemical Structure and Classification
Exemestane is chemically described as 6-methylenandrosta-1,4-diene-3,17-dione, making it structurally related to the natural androgen substrate androstenedione. 2 This steroidal structure is fundamental to how the drug works and distinguishes it from nonsteroidal aromatase inhibitors like anastrozole and letrozole. 1
Mechanism Related to Steroidal Nature
The steroidal structure of exemestane allows it to act as a "false substrate" for the aromatase enzyme. 2 Specifically:
- Exemestane binds irreversibly to the catalytic site of aromatase, causing permanent enzyme inactivation through a mechanism called "suicide inhibition" 1, 2
- This contrasts with nonsteroidal aromatase inhibitors (letrozole, anastrozole), which bind reversibly to the heme group of the enzyme 1
- The irreversible binding contributes to sustained estrogen suppression that persists for 4-5 days after a single dose 2
Clinical Implications of Its Steroidal Nature
Because exemestane has androgenic properties due to its steroidal structure, researchers initially hypothesized it might have less impact on bone loss compared to nonsteroidal aromatase inhibitors. 1 However, clinical trial data from the Intergroup Exemestane Study (IES) showed that fracture incidence at 58 months was actually significantly higher with exemestane (7%) compared to tamoxifen (5%), dispelling this hypothesis. 1
The NCCN Breast Cancer Guidelines Panel considers all three selective aromatase inhibitors (anastrozole, letrozole, exemestane) to be similar in antitumor activity and toxicity profiles, despite the structural difference between steroidal and nonsteroidal agents. 1
Important Clarification
While exemestane is a steroid by chemical structure, it does not contain corticosteroids or anabolic steroids in the traditional sense that patients often worry about. 2 Exemestane has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone, and has no effect on other enzymes involved in the steroidogenic pathway up to concentrations at least 600 times higher than those that inhibit aromatase. 2
Practical Considerations
- The steroidal nature of exemestane means it may be tried after failure of nonsteroidal aromatase inhibitors (or vice versa), as cross-resistance is not complete 3, 4
- Androgenic events have been reported in a small number of patients receiving high doses (200 mg daily) but are rarely reported at the recommended 25 mg daily dosage 4, 5
- The drug's steroidal structure does not translate to the side effects typically associated with corticosteroid or anabolic steroid use 4, 6, 7