Glucocorticoids and sex hormones
Glucocorticoids (Prednisolone, Dexamethasone) potently inhibit lymphoid tissue proliferation. They are prescribed for leukemias and lymphomas. Remission occurs rapidly, but over time drug efficacy decreases and relapse is inevitable. They are also used as adjuvants to manage tumor complications and chemotherapy side effects: nausea, vomiting, hemolysis, hypercalcemia, and elevated intracranial pressure.
Androgens (Testosterone propionate, Prolotestosterone) are used for breast cancer in women with preserved menstrual function or within the first 5 years of menopause. They suppress estrogen production but cause virilization, dizziness, and nausea.
Estrogens (Diethylstilbestrol, Fosfestrol, Chlortalidone) are effective in prostate cancer (they suppress natural androgens, causing gynecomastia and impotence) and advanced postmenopausal breast cancer — more than 5 years (they reduce androgen synthesis by suppressing gonadotropins). 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 inferior in efficacy to aromatase inhibitors.
Antihormonal drugs (Antagonists)
Synthetic non-steroidal antiandrogens (Flutamide, Nilutamide, Bicalutamide) compete with hormones for receptors in target organs and block the translocation of the receptor-androgen complex into the nucleus. They are used orally for prostate cancer. Monotherapy causes a reflex surge in luteinizing hormone (LH) and testosterone, so they must be combined with gonadotropin-releasing hormone (GnRH) analogs. Side effects include gynecomastia and liver dysfunction, while specifically for nilutamide — 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 cessation of hormone-dependent cell growth regardless of the cycle phase. They are used orally for postmenopausal breast cancer. They 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, skin). First-generation drugs (Aminoglutethimide) were non-selective and required glucocorticoid coverage (Hydrocortisone). Modern agents (Anastrozole, Letrozole, Exemestane) are highly selective and used orally without coverage. They cause nausea and fatigue, while exemestane, due to its steroidal structure, causes hot flashes, acne, and alopecia.
GnRH analogues (Leuprorelin, Goserelin) act on the Hypothalamus–Adenohypophysis axis. Unlike natural pulsatile secretion, depot formulations provide a stable concentration of the substance. This leads to receptor desensitization, a drop in LH and FSH levels, and a decrease in sex hormone production. They are prescribed subcutaneously or intramuscularly for prostate, uterine, and breast cancer. They cause impotence, hot flashes, and increase the risk of secondary tumors.
To remember the indications for breast cancer, use the "5-year rule": if menopause has lasted LESS than 5 years (or the menstrual cycle is preserved), androgens are prescribed. If menopause has lasted MORE than 5 years, estrogens or antiestrogens are prescribed.
Class and exam questions
Why cannot antiandrogens be used as monotherapy?
Receptor blockade by antiandrogens (e.g., flutamide) removes the inhibitory effect of testosterone on gonadotropin secretion. This causes a reflex surge of LH and a new spike in testosterone production, which is why combination with GnRH analogues is required.
What is the advantage of modern aromatase inhibitors over first-generation drugs?
First-generation drugs (aminoglutethimide) were non-selective and suppressed the synthesis of all steroids, requiring mandatory hydrocortisone coverage. Modern drugs (anastrozole, letrozole) selectively block only estrogen synthesis and do not require glucocorticoid administration.
How do GnRH analogues work if the natural hormone stimulates the reproductive system?
The therapeutic effect is achieved by maintaining a stable concentration of the drug in the blood using depot forms. Unlike physiological pulsatile secretion, continuous exposure causes pituitary receptor desensitization and the complete cessation of gonadotropin production.
What else to study on this topic
- Mechanisms of glucocorticoid resistance development in lymphoma therapy.
- Differences in tissue specificity of selective estrogen receptor modulators (SERMs).
- Regimens for dexamethasone administration as adjuvant therapy to manage side effects.
- Impact of the steroid structure of exemestane on its adverse reaction profile.
- Pharmacokinetic features of depot formulations of gonadotropin-releasing hormone analogues.
Master the entire topic in the «Pharmacology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Hormonal Antineoplastic Agents" and 5,304 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 116 video lessons on the subject
Other topics in the "Antineoplastic agents" section
Free video lessons: pharmacologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.