Physiological Rationale and Evolution of the Drug Class
In postmenopausal women, ovarian function declines, and the ovaries cease to be the primary source of sex hormones. During this period, the extra-adrenal (peripheral) pathway of estrogen synthesis becomes predominant. It takes place in the liver, adipose tissue, skin, and breast tissue itself. The key enzyme in this process is aromatase.
Historically, the first drugs to block this pathway were first-generation inhibitors (aminoglutethimide). Their major drawback was low selectivity: they non-selectively suppressed the synthesis of all steroids, including glucocorticoids and mineralocorticoids. As a result, patients required mandatory hydrocortisone replacement therapy. Modern drugs, such as letrozole, were developed specifically to eliminate this shortcoming—they possess high selectivity and do not require glucocorticoid co-administration.
Mechanism of Action
Structurally, letrozole is classified as a non-steroidal compound. Its pharmacological target is the aromatase enzyme in peripheral tissues.
Letrozole acts as a competitive inhibitor. It reversibly binds to the active site of the enzyme and blocks the biochemical reactions converting androgens to estrogens. Specifically, the drug disrupts the aromatization of androstenedione to estrone and testosterone to estradiol.
Due to its high selectivity, letrozole provides nearly complete inhibition of estrogen synthesis without affecting adrenal cortex hormone production.
Pharmacological Effects and Indications
The main pharmacological effect of letrozole is the induction of a profound estrogen deficiency in the body. Because the growth of certain tumor cells is directly stimulated by estrogens, artificially lowering their levels deprives the tumor of its growth stimulus and reliably suppresses the proliferation of estrogen-dependent tissues.
In clinical practice, letrozole is used as an antineoplastic agent. Its primary indication is the treatment of estrogen-dependent breast cancer. A crucial prerequisite is that the drug is administered exclusively in the postmenopausal period, when peripheral hormone synthesis is dominant.
Adverse Effects
Modern aromatase inhibitors are significantly better tolerated than first-generation drugs. Among general adverse effects, nausea and fatigue are most commonly reported with letrozole therapy.
It is important to differentiate adverse effects within the modern inhibitor class. Unlike steroidal agents (e.g., exemestane), which bind to the enzyme covalently and irreversibly, letrozole lacks a steroidal structure. Therefore, it is not associated with specific complications such as hot flashes, acne, and alopecia.
Formulation and Prescription
The drug is intended for oral administration. It is available as film-coated tablets with a dosage of 0.0025 g (2.5 mg).
Example of a letrozole prescription: ```latin Rp.: Tab. Letrozoli obductas 0.0025 D.t.d. N. 30 S. Take orally, 1 tablet (0.0025 g) once daily. ```