Prostate Cancer (cont.)
Prostate cells are physiologically dependent on androgens hormonal stimulation to grow, function, and proliferate. Testosterone, although not tumorigenic, is essential for the growth and perpetuation of tumor cells. The testes are the source of most androgens. The goal of hormonal therapy is to lower levels of testosterone or to stop testosterone from working. This can be achieved with surgery or with drug treatment. Often, the initial response is good, but cancer may progress over time.
Androgen deprivation therapy: This therapy is likely to be used in cases in which the cancer has spread to distant regions. Therefore, it is not currently used among the standard options for men with localized prostate disease.
- The testes produce much of the testosterone that stimulates cancer growth. Surgical removal of both testicles (castration, or orchiectomy) is the best way to stop hormonal stimulation of the tumor.
- Men usually prefer medical castration to surgical castration. A variety of agents have been used to suppress androgen levels acting at different levels of hormonal production and release.
- Nowadays, GnRH agonists are the most widely used. They induce a medical castration by suppressing luteinizing hormone production and, therefore, the synthesis of testicular androgens. A number of GnRH agonists are available (leuprolide, goserelin, buserelin, and triptorelin).
- GnRH antagonists (degarelix) may be beneficial in cases when immediate decrease in testosterone levels is required.
- Estrogen, in the form of diethylstilbestrol, can also be used to suppress testosterone. Because of its extensive side effects, estrogen is not used very often.
- Antiandrogen monotherapy: Antiandrogens bind to androgen receptors and competitively inhibit their interaction with male hormones (testosterone and dihydrotestosterone).
- Unlike medical castration, antiandrogen therapy does not decrease luteinizing hormone (LH) levels and androgen production. Rather, testosterone levels are normal or increased. Thus, men treated with antiandrogen monotherapy do not have the full spectrum of side effects attributable to low levels of testosterone, and many maintain some degree of potency.
- These agents are usually used in combination with a GnRH agonist either continuously or for 2 to 4 weeks during the initiation of treatment with a GnRH agonist. This is also known as "complete androgen blockade."
- The most common agents are flutamide (Eulexin), bicalutamide (Casodex) and nilutamide.
- Drugs that stop the adrenal glands from making androgens are sometimes used.
- Side effects of these medications vary. Orchiectomy and LHRH agonists may cause impotence, hot flashes, and loss of sexual desire, osteoporosis, and bone fractures. Antiandrogens may cause nausea, vomiting, diarrhea, and breast enlargement or tenderness. Any of these therapies can weaken bones.
Pierre-Alain Hueber, MD, PhD
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