Androgen deprivation therapy (ADT) is a treatment for certain types of prostate cancer. The prostate is the walnut-sized gland underneath the male bladder that is responsible for producing the fluid that nourishes sperm.
How sex hormones work
Androgens are hormones that are produced naturally by the body and that control the development and maintenance of gendered sex traits. For males, one of the more important androgens is testosterone, which is produced in the testicles. Normally, the hypothalamus (a small portion of the brain, sometimes called the “master switch”) produces a hormone called LHRH, or luteinizing hormone-releasing hormone. LHRH signals to the pituitary gland (a gland in the brain that is sometimes called the “master gland”) to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In men, LH and FSH signal the testicles to produce testosterone.
What is ADT?
In some forms of prostate cancer, testosterone can increase cancer growth. ADT is a treatment that reduces the levels of testosterone in the body. There are several strategies to do this: LHRH inhibitors, anti-androgens, androgen synthesis inhibitors, and estrogens.
There are two strategies for inhibiting the production of LHRH from the hypothalamus — LHRH agonists and antagonists.
LHRH agonists are synthetic proteins that are similar to LHRH and that bind to the LHRH receptor in the pituitary gland. Initially, LHRH agonists stimulate LH production, but continuing the treatment at high levels causes the pituitary gland to become insensitive to the signal from the LHRH receptor. As a result, LH production stops. This, in turn, reduces testosterone production in the testicles.
In the beginning, these treatments can cause something called “testosterone flare” in which the testicles produce a burst of testosterone in response to the first binding of the treatment to LHRH receptors. This flare can worsen symptoms, so this type of treatment is usually given in combination with an anti-androgen therapy in the first few weeks of treatment. There are four LHRH agonists approved to treat prostate cancer in the U.S.: leuprolide, goserelin, triptorelin, and histrelin.
LHRH antagonists are therapies that block LHRH from binding to the LHRH receptor but that do not activate the receptor. This type of therapy does not cause a testosterone flare. One LHRH antagonist, degarelix, is currently approved to treat advanced prostate cancer in the U.S.
Not all male hormones are made by the testicles. A small amount of male hormone is made by the adrenal glands (small glands over the kidneys), and may not be affected by LHRH inhibitors.
An antiandrogen is a medication that can block the effect of the remaining male hormone on prostate cancer cells. They are usually prescribed along with an LHRH agonist to decrease the risk of a testosterone flare. They include bicalutamide, flutamide, enzalutamide, and nilutamide.
Androgen synthesis inhibitors
Androgen synthesis inhibitors are medications that lower testosterone levels by blocking testosterone production. Androgen synthesis inhibitors work by inhibiting an enzyme called CYP17. This enzyme, which is found in testicular, adrenal, and prostate tumor tissues, is necessary for the body to produce testosterone from cholesterol.
Abiraterone acetate is approved in combination with prednisone (a corticosteroid) to treat metastatic high-risk castration-sensitive prostate cancer and metastatic castration-resistant prostate cancer. Prior to the approval of abiraterone, two therapies approved to treat conditions other than prostate cancer, ketoconazole and aminoglutethimide, were sometimes used off-label as second-line treatments for prostate cancer that was resistant to other therapies.
Some patients who would require lifetime ADT may elect to undergo an orchiectomy, surgical removal of the testicles. Orchiectomy is a permanent method of reducing testosterone production used in patients with stage IV (metastatic) prostate cancer.
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