Advanced Prostate Cancer
Hormone Therapy for Advanced Prostate Cancer
Medically reviewed by Dr. Paul Song M.D
hormones (androgens) are like fuel for prostate tumors; they can’t grow without them. Conventional hormone therapy is designed to reduce the levels of these fueling hormones—mainly testosterone and dihydrotestosterone (DHT)—which in turn starves the tumor. Although hormone therapy for advanced prostate cancer doesn’t cure the disease, it can slow the growth of prostate cancer or even cause the tumors to shrink.
Who Is a Candidate for Hormone Therapy?
Hormone therapy for advanced prostate cancer is not for every man who has prostate cancer. It is typically recommended:
- For men whose prostate cancer has already moved beyond the gland and has invaded nearby or distant parts of the body
- Before surgery or radiation in an attempt to shrink the tumor and enhance the effectiveness of the other therapies
- In combination with radiation therapy in certain men whose cancers are likely to return after therapy
- For men who have already had surgery or radiation and their cancer has returned
Which Medications Are Prescribed for Hormone Therapy for Advanced Prostate Cancer?
Use of certain medications is the most common approach to hormone therapy for advanced prostate cancer. This therapy is also known as chemical castration because the drugs (chemicals) figuratively castrate men by stopping their hormone (androgen) production.
The medications used for hormone therapy can be grouped into five categories:
- LH-RH agonists. LH-RH is shorthand for luteinizing hormone-releasing hormone agonists, which means these drugs achieve the same purpose as surgical removal of the testes—they drastically reduce the supply of testosterone by preventing the testicles from getting the order from the pituitary gland to produce the hormone. Unlike surgery, however, the effects of LH-RH agonists can be reversed. Drugs in this category include Lupron, Viadur, and Zoladex, and they all are given via injection every three or four months. Their side effects include hot flashes, osteoporosis, erectile dysfunction, and reduced sexual desire. Depending on the condition of your cancer, your doctor may recommend taking the drugs for several months or for longer, even for the rest of your life.
- Anti-androgens. Although the testicles are the main manufacturing source of testosterone, a small amount is also made in the adrenal glands. Therefore blocking production of testosterone in the testicles does not stop the hormone completely, meaning you need to halt the other source as well. That’s where the anti-androgens come in. Casodex (bicalutamide), Eulexin (flutamide), and Nilandron (nilutamide) are used for this purpose. Unlike LH-RH agonists, these medications are taken in pill form. Anti-androgen therapy is not effective alone, for it only blocks the relatively small amount of testosterone from the adrenals. But when it teams up with an LH-RH agonist, together they can starve the prostate cancer cells. Side effects of the anti-androgens include diarrhea, impotence, breast development, and dizziness.
- Estrogens. Yet another approach is to use the female hormone estrogen to interfere with the production of testosterone in the testicles. This used to be the first line of hormonal therapy, but the side effects were a real concern—blood clots, headache, chest pain, depression, and breast development. Fortunately the LH-RH agonists and anti-androgens moved in to take their place in the hormonal treatment area. Today estrogen therapy is typically reserved for men who have tried the other hormonal approaches and they no longer work.
- Androgen synthesis inhibitors. Thus far, there is only one drug in this category: Zytiga (abiraterone). Zytiga was approved in April 2011 for treatment of men who have metastatic prostate cancer that has resisted other types of hormone therapy or treatment with docetaxel. Unlike other hormone therapies, Zytiga reduces the production of a protein and hormone called cytochrome P450 17A1, which is necessary for the production of testosterone. Zytiga can reduce production of testosterone in three sites: the testicles, adrenal glands, and the prostate tumor.
- Androgen inhibitors. The first member of this drug class is Xtandi (enzalutamide). Xtandi was designed to block the activity of testosterone when the hormone attempts to attach to prostate cancer cells. Candidates for enzalutamide are men who have advanced prostate cancer that has spread despite treatment with hormone therapy and chemotherapy (docetaxel).
One significant problem with conventional hormonal therapy is that it grows less effective over time, as the minority of prostate cancer cells that are not affected by the therapy multiply and become a larger portion of the cancer.
What Type of Surgery Is a Form of Hormone Therapy?
Although the majority of hormone therapy options involve medications, one does not. A surgical procedure known as an orchiectomy (removal of the testicles) also can be used as a type of hormone therapy for prostate cancer. When surgeons remove the testicles, this eliminates the main source of male hormone production. This is a radical move, however, and obviously irreversible, which is why some men opt for the medications. When men stop taking the drugs, their hormone production can return to normal.
What Side Effects Are Associated with Hormone Therapy?
The number and severity of side effects you may experience with hormone therapy will depend on several factors, including which option you choose, how long you remain on hormone therapy, age, stage and grade of cancer, and whether you are using other therapies, including alternative/complementary therapies.
- Breast pain and enlargement: Also known as gynecomastia, symptoms include sensitive and/or painful nipples and/or an increase in the amount of breast tissue resulting in enlarged breasts. This side effect is associated with anti-androgen and estrogen use.
- Cardiovascular events: Continuous estrogen therapy is associated with cardiovascular risks, including blood clots and stroke. Taking anti-clotting medication along with estrogen can reduce these risks.
- Cholesterol level changes: Use of anti-androgens can lower high-density lipoprotein (HDL; “good”) cholesterol when combined with LH-RH treatment. In addition, LH-RH treatment alone can significantly increase triglycerides. On the positive side, LH-RH can also increase HDL levels.
- Diarrhea and/or constipation: These side effects are associated with the use of anti-androgens.
- Erectile dysfunction/loss of libido: Use of anti-androgens and LH-RH agonists is associated with erectile dysfunction, while LH-RH agonists can also reduce libido.
- Fatigue: Anti-androgens, LH-RH agonists, and estrogen can all cause some degree of fatigue.
- Hair and skin changes: Men may notice some hair growth on the head and hair loss on the rest of the body when using anti-androgens or LH-RH agonists. Dry skin can also occur after using these hormone therapies for several months.
- Hot flashes: Whenever you reduce the level of male hormones, you run the risk of experiencing hot flashes. The frequency and severity of hot flashes varies very dramatically from one man to another.
- Osteoporosis: Any hormone therapy that reduces the levels of male hormones can contribute to the development of osteoporosis. The severity of bone loss depends on several factors, including a man’s bone health before therapy began, the length of hormone therapy, other efforts a man is taking to reduce bone loss, and history of fractures.
- Penis/scrotum shrinkage: Any reduction in male hormone levels can potentially reduce the size of the penis and scrotum.
- Weight and/or belly fat gain: Anti-androgens and LH-RH agonists can contribute to weight gain and the accumulation of belly fat.