There are two types of hormone therapy for prostate cancer: conventional and hormone balancing using bio-identical hormones. Male hormones are like fuel for prostate tumors, which cannot grow without them. Conventional hormone therapy is designed to reduce the levels of the fueling male hormones—primarily testosterone and dihydrotestosterone (DHT)—and thereby starve the tumor. Although hormone therapy does not cure cancer, it can slow the growth of prostate cancers, or even cause them to shrink.
Hormone therapy 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
Surgery can also be used as a type of hormone therapy. When surgeons remove the testicles (orchiectomy), 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 “chemical castration,” which is not physical castration but simply means taking drugs to stop male hormone production. When men stop taking the drugs, their hormone production can return to normal.
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: abiraterone (Zytiga). Abiraterone 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, abiraterone reduces the production of a protein and hormone called cytochrome P450 17A1, which is necessary for the production of testosterone. Abiraterone 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 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.
Side Effects of Hormone Therapy
- 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.
Finasteride, DHT and Prostate Cancer
Finasteride (Proscar) is a 5-alpha-reductase inhibitor used to treat benign prostatic hypertrophy (BPH). When scientists noticed that finasteride inhibited the conversion of testosterone to DHT, they initiated a study called the Prostate Cancer Prevention Trial (PCPT) in the early 1990s. (Thompson 2003) The trial evaluated 18,000 men age 55 and older and lasted seven years. The results, published in 2003, found that:
- 18.4 percent of men who took finasteride developed prostate cancer over the study’s course
- 24.4 percent who took placebo developed prostate cancer over the study’s course
- Men in the finasteride group had a 28 percent reduction in prevalence in prostate cancer and a smaller prostate volume than men in the placebo group
- The rate of high-grade cancers was greater in the finasteride group (6.5%) than in the placebo group (5.1%). The reason for this is unknown.
- Most cancers in the finasteride group were small and localized.
The incidence of high-grade cancers in the finasteride group during this study is one reason medical professionals are reluctant in most instances to prescribe finasteride for prostate cancer treatment.
Since the PCPT, subsequent studies have reinterpreted the findings. Some research confirmed the reduced risk of prostate cancer (Thompson 2008), while others re-examined the increased risk of high-grade tumors and determined that finasteride actually reduced the risk of developing aggressive cancer when compared with placebo. (Pinsky 2008; Redman 2008)
However, two physicians from Johns Hopkins evaluated all the findings and note that the decrease in prostate cancer related to finasteride was much smaller than originally reporte and not statistically significant. Therefore, they believe finasteride will not significantly help reduce the risk of prostate cancer among men who are monitored regularly and who have a biopsy when they experience an elevated PSA or abnormal digital rectal exam. They recommend men not take 5-alpha-reductase inhibitors as a means to prevent prostate cancer, and warn that because 5-alpha reductase inhibitors reduce PSA levels by about 50 percent, men should multiply their PSA numbers during the first two years they use the drugs, by 2.3 for years 2 through 7, and by 2.5 for 7 years or longer to get a more accurate indication of their prostate cancer risk that may require a biopsy. (Johns Hopkins)
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