Hormone therapy will likely be one of your main treatments if you have advanced prostate cancer. That’s cancer that has spread to other parts of your body or has come back after treatment.
Also called androgen deprivation therapy, androgen suppression therapy, and testosterone depleting therapy, it helps stop cancer cells from growing by blocking their main source of fuel – male sex hormones called androgens. It’s not a cure, but hormone therapy can keep prostate cancer under control, sometimes for years.
The most common androgens are testosterone and dihydrotestosterone. Everyone has them, but you have more if you were assigned male at birth. Your testicles make most of your testosterone, and some of that gets changed into dihydrotestosterone.
Hormone therapy for advanced prostate cancer works in two ways: by stopping your body from making androgens and by keeping cancer cells from using these hormones. There are several different methods and classes of drugs that can be used in this treatment.
Luteinizing Hormone-Releasing Hormone (LHRH) Agonists
LHRH agonists are drugs that block the production of testosterone where most of it begins: in your brain.
When your androgen levels are low, an area of your brain called the hypothalamus sends a chemical called luteinizing hormone-releasing hormone (LHRH) to your nearby pituitary gland. That causes this gland to make luteinizing hormone (LH), which signals your testicles to make testosterone.
Taking an LHRH agonist floods your system with an imitation form of this hormone. That causes a temporary surge in your testosterone production, called a testosterone flare. But it also causes your body to stop making LHRH naturally. Soon, your pituitary gland stops responding to the LHRH agonist, and your testicles don’t get the message to make testosterone. This is called medical castration.
LHRH agonists used to treat prostate cancer include:
- Goserelin (Zoladex), a small pellet that’s implanted under the skin on your belly either monthly or every three months
- Leuprolide (Camcevi, Eligard, Lupron, Lupron Depot), a shot you get between once a month and twice a year
- Triptorelin (Trelstar), a shot you get between once a month and twice a year
This may be the first type of hormone therapy your doctor prescribes.
Because an LHRH agonist can cause your testosterone levels to rise at first, your prostate cancer symptoms may get worse for a few weeks. Your doctor may give you another kind of drug called an antiandrogen before or while you take an LHRH agonist to prevent this.
Luteinizing Hormone-Releasing Hormone (LHRH) Antagonists
LHRH antagonist drugs are another form of medical castration that work in a different way. They keep your natural LHRH from reaching its target in your pituitary gland, which stops the production of testosterone in your testicles. Your doctor might prescribe:
- Degarelix (Firmagon), a shot you get once a month
- Relugolix (Orgovyx), a pill you take every day
Unlike LHRH agonists, these drugs don’t cause a testosterone flare.
Surgery
Another way to stop your body from making most testosterone is a procedure called an orchiectomy, or surgical castration. A surgeon removes your testicles, and testosterone levels are then reduced.
It’s usually an outpatient procedure, meaning you won’t have to spend the night in the hospital. Some men don’t like the look of their scrotum after the testicles are removed, and you may choose to have implants.
Surgical castration can lower your testosterone levels by 90% to 95%. This might be an option for you if you don’t want to take medication, but you should know that the procedure can’t be reversed.
CYP17 Inhibitors
For people with advanced prostate cancer that is resistant to other kinds of hormone therapy, newer drugs called CYP17 inhibitors may be an option. These are also called androgen synthesis inhibitors.
While your testicles make most of your body’s testosterone, a small amount is made in your adrenal glands and sometimes by prostate cancer cells themselves. An enzyme called CYP17 is key to this process. Inhibitor drugs reduce production of testosterone by cells in the body. Options include:
- Abiraterone (Zytiga), pills you take once a day
- Ketoconazole (not an FDA-approved prostate cancer treatment, but sometimes used off-label)
These drugs also lower the levels of other important hormones in your body, including cortisol. That means you need to take them along with a steroid, like prednisone.
They’re approved for use in metastatic prostate cancer, which is cancer that has spread far beyond your prostate.
There’s some evidence to show that Black men may respond better to the CYP17 inhibitor abiraterone than White men. Not a lot of research has been done, but some studies have found abiraterone may work better to lower prostate-specific antigen (PSA) levels in Black men than in White men, and could help them live longer. But Black men are less likely than White men to get this drug or other newer hormone therapy medications.
Antiandrogens
This type of drug keeps prostate cancer cells from using androgens as fuel. They block the receptors in prostate cells where androgens would normally attach.
Older antiandrogens still being used include:
- Bicalutamide (Casodex), a pill you take once a day
- Flutamide (Eulexin), pills you take three times a day
- Nilutamide (Nilandron), a pill you take once a day
Cancer cells can sometimes become resistant to these drugs. In that case, you might get a newer type of antiandrogen. These are:
- Apalutamide (Erleada), a pill you take once a day
- Darolutamide (Nubeqa), a pill you take twice a day
- Enzalutamide (Xtandi), pills you take once a day
You might get one of these drugs on its own if other forms of hormone therapy stop working. They can also prevent symptoms of a testosterone flare that happen when you start taking an LHRH agonist. But they’re most often prescribed along with another type of hormone therapy.
Combination Treatment
This method fights advanced prostate cancer on two fronts: by both lowering the amount of testosterone your body makes, and by keeping cancer cells from using any androgens that remain. This treatment is also called combined or complete androgen blockade.
You’ll either have surgery to remove your testicles or take an LHRH drug, and also take an antiandrogen.
Other Drugs You May Take With Hormone Therapy
While you’re being treated with hormone therapy for advanced prostate cancer, you may have some uncomfortable side effects that affect your quality of life. Your doctor can prescribe other medications to help with these, for example:
Bone strengtheners. Because hormone therapy can cause bone loss, you may take medication to slow or reverse it. These include bisphosphonates (Fosamax, Zometa) and denosumab (Prolia, Xgeva).
Antidepressants. These drugs can help with possible side effects of hormone therapy such as hot flashes and mood changes.
Resistance to Hormone Therapy
Hormone therapy is usually able to control the growth of prostate cancer for at least some amount of time, possibly for years. But eventually, most prostate cancer becomes castration resistant, meaning it is able to grow even when androgen levels are very low. In that case, you may need to switch to a different hormone therapy medication or try a different type of treatment.
Show Sources
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SOURCES:
Urology Care Foundation: “What is Advanced Prostate Cancer?” “Hormone Therapy.”
American Cancer Society: “Initial Treatment of Prostate Cancer, by Stage and Risk Group,” “Hormone Therapy for Prostate Cancer.”
Endocrine Reviews: “Hormonal Therapy for Prostate Cancer.”
Johns Hopkins Medicine: “Hormone Therapy for Prostate Cancer.”
Prostate Cancer UK: “How does hormone therapy work?”
National Cancer Institute: “Hormone Therapy for Prostate Cancer,” “Dihydrotestosterone.”
Cleveland Clinic: “Androgens.”
Medscape: “leuprolide (Rx),” “goserelin (Rx),” “triptorelin (Rx),” “abiraterone (Rx),” “flutamide (Rx),” “bicalutamide (Rx),” “nilutamide (Rx),” “apalutamide (Rx),” “enzalutamide (Rx).”
BMC Cancer: “A review of new hormonal therapies for prostate cancer in black men: is there enough data?”
JAMA Network Open: “Racial and Ethnic Disparities in Use of Novel Hormonal Therapy Agents in Patients With Prostate Cancer.”
Journal of Hematology Oncology Pharmacy: “Comparison of Second-Generation Antiandrogens for the Treatment of Prostate Cancer.”
