The male sex hormone testosterone (a type of hormone known as an androgen) is known to stimulate the growth of prostate cancer cells. Hormone therapy, depending on the form, reduces this effect by either decreasing the body’s production of testosterone or blocking testosterone from binding to cancer cells. (1) There are several scenarios in which hormone therapy is typically used:
When prostate cancer has spread too far to be cured by surgery or radiation, or has recurred after surgical or radiation treatment.As an initial treatment (along with radiation therapy) for patients who are at higher risk of recurrence after treatment, such as those with a high PSA (prostate-specific antigen) level or a high Gleason score (a grade, based on an evaluation of a tissue biopsy of the tumor, that suggests how aggressive a case of prostate cancer is). (2)For patients who have a high PSA level following surgery or radiation, even if they have no evidence of disease — although not all doctors agree with this approach.
Doctors use several types of medication to lower testosterone levels, but these therapies do so only temporarily. When you stop taking them, testosterone levels begin to rise again. Here are some of the most commonly used hormone therapies. Luteinizing Hormone-Releasing Hormone (LHRH) Agonists and Antagonists LHRH is one of the key hormones released by the body before testosterone is produced. LHRH agonists and antagonists lower testosterone levels by blocking the release of LHRH. Treatment with these drugs is sometimes called medical castration because they lower androgen levels as much as orchiectomy, or removal of the testicles, does. (2) LHRH agonists and antagonists include:
goserelin (Zoladex)triptorelin (Trelstar)histrelin (Vantas)degarelix (Firmagon)
CYP17 Inhibitors An LHRH agonist or antagonist can stop the testicles from making androgens, but other cells in the body (including prostate cancer cells) still make small amounts of androgens. These small amounts of hormones can continue to stimulate cancer growth. The medication abiraterone (Zytiga) blocks a key enzyme involved in androgen production called the CYP17 enzyme. Zytiga can be used to treat metastatic prostate cancer that has become resistant to traditional hormone therapies. (3) Anti-Androgens For most prostate cancer cells to grow, androgens have to attach to a protein in the prostate cancer cell called an androgen receptor. Anti-androgens are drugs that also connect to these receptors. “The testosterone can’t hit its target because there is something already there,” explains Mark Pomerantz, MD, a medical oncologist at the Dana-Farber Cancer Institute in Boston. Traditional anti-androgens may be given along with LHRH agonists and antagonists. They include:
flutamide (Eulexin)bicalutamide (Casodex)nilutamide (Nilandron)
Doctors now have access to a newer type of anti-androgen that interferes with androgen function even more effectively. “These newer agents bind to the androgen receptor much more tightly and also seem to break up the androgen receptor,” explains Dr. Pomerantz. They may be used along with an LHRH agonist or antagonist as a first-line hormonal therapy or added later if traditional hormone treatments are not working. Next-generation anti-androgens include:
enzalutamide (Xtandi)apalutamide (Erleda)darolutamide (Nubeqa)
In many men, however, some cells gain the ability to grow even in the low-testosterone environment created by hormone therapy. As these hormone therapy-resistant prostate cancer cells continue to multiply, the hormone therapy, not surprisingly, has less and less effect on the growth of the tumor. Prostate cancer that is no longer responding to hormone therapy is referred to as castration-resistant prostate cancer. (4) Fortunately, men with castration-resistant prostate cancer have more options for treatment than ever before. “At that point, we can add something new, such as a newer hormonal agent, chemotherapy, or a different chemotherapy, if you had one up front, or an immunotherapy,” explains Ornstein. RELATED: 9 Myths About Prostate Cancer Some doctors think that hormone therapy works better if it’s started as soon as possible, even if a man is not having any symptoms. Other doctors feel that, because of the side effects of hormone therapy and the chance that the cancer could become resistant to the therapy, treatment shouldn’t be started until symptoms develop. This issue is being actively studied. (2) The potential effects of testosterone deprivation include:
Hot flashesNight sweatsWeight gainFatigueIrritabilityMood changes/depressionDecrease in libidoErectile dysfunctionLoss of muscle massBone thinning (osteoporosis)
Many of these side effects can be prevented or treated, according to the American Cancer Society. (2) Hot flashes can often be controlled with certain antidepressants or other drugs, for example. A number of drugs are used to help prevent and treat bone thinning or osteoporosis. Depression can be alleviated with antidepressants and counseling. Exercise can fend off multiple side effects, including fatigue, weight gain, and loss of bone and muscle mass.
