Types of Hormone Therapy for Prostate Cancer
Androgens (male hormones) stimulate the growth of prostate cancer cells. In men, the main androgen is testosterone. Hormone therapy reduces androgens or prevents them from reaching prostate cancer cells. Several types of hormone therapy are available, including LHRH agonists, LHRH antagonists, anti-androgens, androgen-synthesis inhibitors, new generation anti-androgens, other drugs, and surgical removal of the testicles.
LHRH agonists, the most common form of hormone therapy for prostate cancer, lower the amount of testosterone made by the testicles. LHRH stands for luteinizing hormone-releasing hormone. When the hypothalamus (part of the brain) detects low testosterone levels, it releases LHRH. This signals the pituitary gland to release another hormone that in turn signals the testicles to produce testosterone.
LHRH agonists cause a temporary rise in testosterone in your body, known as a tumor flare, which may cause pain and make other symptoms worse at first, although this is rare. To prevent a flare, your doctor may give you an anti-androgen along with the LHRH agonist for the first few weeks. The agonists then suppress the pituitary gland from signaling for testosterone to be produced, and testosterone drops to a level seen with surgical removal of the testicles. Depending on the dose, these drugs are typically given as an injection under the skin or into a muscle every one, three, four, or six months.
LHRH agonists include:
- Leuprolide, leuprorelin (Lupron, Viadur, Eligard)
- Goserelin (Zoladex)
- Triptorelin (Trelstar)
- Histrelin (Vantas)
LHRH antagonists work by binding to LHRH receptors. This interrupts a cell signaling process and interferes with the production of testosterone in the testicles and adrenal glands. LHRH antagonists reduce testosterone levels more quickly than LHRH agonists and do not cause tumor flare like LHRH agonists. Degarelix (Firmagon), an LHRH antagonist, is given as a monthly injection under the skin.
Even without testicular testosterone, the adrenal glands and other cells still make small amounts of androgens. Anti-androgens are androgen-receptor antagonists—they bind to androgen receptors. This prevents testosterone from binding to these receptors, thus slowing cancer growth.
Anti-androgens are not typically used alone. They may be given before treatment with or in combination with LHRH agonists. They are typically taken by mouth and include:
- Bicalutamide (Casodex)
- Nilutamide (Nilandron)
- Flutamide (Eulexin)
An androgen-synthesis inhibitor is an improvement on other hormone therapies because it can drop testosterone levels in a man's body lower than any other known treatment, and it lowers testosterone in the prostate cancer itself. Because castration-resistant prostate cancer grows in the presence of very low levels of testosterone, an androgen-synthesis inhibitor may be a better treatment option for men with castration-resistant disease.
Approved in 2011, abiraterone (Zytiga) blocks the synthesis of testosterone in the testicles, the adrenal glands, and prostate cancer cells. It is typically used in combination with prednisone to treat castration-resistant prostate cancer that has spread to other parts of the body and has not gotten better with other hormone therapy. It is taken as a daily pill and may be used before or after chemotherapy.
New Generation Anti-Androgens
A more effective anti-androgen, sometimes referred to as a super anti-androgen, enzalutamide (Xtandi, MDV3100) blocks the receptor for testosterone more effectively than previously used anti-androgens. Enzalutamide was approved by the U.S. Food and Drug Administration in 2013 for use after chemotherapy in men with metastatic, castration-resistant prostate cancer. It is taken as a daily pill.
Other Drug-Based Hormone Therapies
Estrogens (female hormones) were once a mainstay in the treatment of advanced prostate cancer. However, because of their possible side effects, other hormone therapy drugs have mostly replaced them. Still, estrogens may be tried if androgen deprivation is no longer working.
Ketoconazole (Nizoral) also blocks androgen production. Since it quickly lowers testosterone levels, it is used most often in men with advanced, metastatic prostate cancer. It may also be used if other forms of hormone therapy are no longer working. It is typically given with a corticosteroid, such as hydrocortisone.
There are several other promising new medicines that may be available only through clinical studies. In addition, studies are being done to see when it is best to start hormone therapy (early versus delayed treatment), whether there are benefits to intermittent versus continuous hormone therapy, and whether it is better to combine different types of hormone therapy.
A less common type of hormone therapy, orchiectomy is the surgical removal of the testicles. Although this is technically a surgical procedure, it is considered hormone therapy because the removal of the testicles is intended to eliminate testosterone production. This simple outpatient procedure is an inexpensive and effective way to reduce androgen levels in the body. However, unlike some of the other methods of lowering testosterone levels, it is permanent, and many men prefer drug-based hormone therapy.