How does letrozole work in the body?
Letrozole is an aromatase inhibitor. It lowers estrogen levels by blocking the enzyme aromatase, which normally converts androgen hormones into estrogens (including estradiol and estrone) in tissues such as fat and muscle. With aromatase inhibited, less estrogen is produced, which helps starve some hormone-dependent cancers of the estrogen they need to grow.
What enzyme does letrozole inhibit, and why does that matter for hormone-sensitive tumors?
Aromatase (CYP19A1) is the key drug target because it is responsible for much of the body’s peripheral estrogen production after menopause. In postmenopausal breast cancer, estrogen can drive tumor growth through estrogen receptors. By reducing circulating estrogen, letrozole reduces stimulation of estrogen receptor signaling in estrogen-receptor–positive tumors.
Does letrozole lower estrogen the same way in all patients?
Letrozole’s effect depends on how much estrogen production is driven by aromatase. In postmenopausal people, peripheral conversion via aromatase is a major estrogen source, so aromatase inhibition produces a marked estrogen decrease. In premenopausal settings, the ovaries can still produce estrogen, so estrogen levels may not drop as dramatically unless combined with other ovarian-suppressing strategies.
What other hormones does aromatase inhibition affect?
Because aromatase converts androgens into estrogens, blocking it shifts the balance away from estrogen synthesis. This can lead to changes in sex-hormone levels consistent with reduced estrogen production, which is the therapeutic goal in hormone-driven disease.
What do patients typically feel from reduced estrogen?
When estrogen falls, patients can experience symptoms related to hypoestrogenism, such as hot flashes, joint or muscle aches, and vaginal dryness. These effects are a common clinical consequence of aromatase inhibition rather than a direct toxic effect on organs.