Glucocorticoids and Sex Hormones
Glucocorticoids (prednisolone, dexamethasone) potently inhibit the proliferation of lymphoid tissue. They are prescribed for leukemias and lymphomas. Remission occurs rapidly, but drug efficacy decreases over time and relapse is inevitable. They are also used as adjuvants to manage tumor complications and chemotherapy side effects, such as nausea, vomiting, hemolysis, hypercalcemia, and elevated intracranial pressure.
Androgens (testosterone propionate, proloteston) are used for breast cancer in women with preserved menstrual function or during the first 5 years of menopause. They suppress estrogen production but cause virilization, dizziness, and nausea.
Estrogens (diethylstilbestrol, phosphestrol, chlortalidone) are effective in prostate cancer (by suppressing natural androgens, leading to gynecomastia and impotence) and advanced breast cancer in late menopause—more than 5 years post-menopause (by decreasing androgen synthesis through gonadotropin suppression). They carry a risk of severe cardiovascular complications (thromboembolism, myocardial infarction, stroke).
Progestins (megestrol acetate, medroxyprogesterone) are prescribed for endometriosis and metastatic breast cancer, although they are generally less effective than aromatase inhibitors.
Antihormonal Agents (Antagonists)
Synthetic nonsteroidal antiandrogens (flutamide, nilutamide, bicalutamide) compete with hormones for receptors in target organs and block the nuclear translocation of the receptor-androgen complex. They are administered orally for prostate cancer. Monotherapy causes a reflex spike in luteinizing hormone (LH) and testosterone, so they must be combined with gonadotropin-releasing hormone (GnRH) agonists. Side effects include gynecomastia and liver dysfunction, with nilutamide specifically causing visual accommodation disturbances.
Antiestrogenic drugs are divided into selective modulators (tamoxifen, toremifene), which can act as agonists or antagonists depending on the tissue, and pure blockers (fulvestrant). They form an unproductive complex with the receptor, leading to receptor pool depletion (down-regulation) and cell cycle-independent arrest of hormone-dependent growth. They are administered orally for postmenopausal breast cancer and may cause uterine bleeding, thromboembolism, visual disturbances, and hypercalcemia.
Enzyme Inhibitors and GnRH Analogs
Aromatase inhibitors block extra-adrenal estrogen synthesis (in the liver, adipose tissue, and skin). First-generation drugs (aminoglutethimide) were non-selective and required glucocorticoid coverage (hydrocortisone). Modern agents (anastrozole, letrozole, exemestane) are highly selective and are administered orally without coverage. They cause nausea and fatigue, while exemestane, due to its steroidal structure, can cause hot flashes, acne, and alopecia.
GnRH analogs (leuprolide, goserelin) act at the level of the hypothalamus-adenohypophysis axis. Unlike physiological pulsatile secretion, depot formulations create a stable drug concentration. This leads to receptor desensitization, a drop in LH and FSH levels, and decreased sex hormone production. They are administered subcutaneously or intramuscularly for prostate, uterine, and breast cancer. They cause impotence, hot flashes, and increase the risk of secondary tumors.