Complications

Hormone treatment has serious side effects. A man should be started on hormone therapy only when it is likely that the benefits of treatment will outweigh the side effects. The most important side effects are the following:

• Hot flashes: Similar to those experienced by women undergoing menopause, these occur in approximately half of men on hormone therapy. They vary from mild flushing to drenching perspiration and may last from a minute to an hour. Medications, including megestrol (Megace), low-dose estrogen compounds, venlafaxine (Effexor), gabapentin (Neurontin), and paroxetine (Paxil), may provide relief.

• Breast tenderness and enlargement: This symptom occurs in approximately one third of men and is more common in those taking antiandrogens, especially after being on the medication for several months.

Hot Flashes

"Menopause" is just another word in the dictionary for most men. While some make a token effort to research and empathize with their mates, in most cases, men feel that it's enough for them to show tolerance as women ''go through the change." It's difficult for men to relate. Few even try.

Sometimes nature has a way of putting the proverbial shoe on the other foot. I've learned the hard way. Even in the biting cold of winter, I find myself having to sleep with both a ceiling fan and a floor fan on trying to cool the hot flashes that I experience throughout the night.

—Charles Williams, That Black Men Might Live

Breast Effects

It is now seven months since I began my hormone suppression therapy. I had no idea that I would miss my testosterone so much. I've nicknamed this therapy Reverse Steroids. This is not just some therapeutic idea that is to be taken lightly. My body is definitely changing. My breasts are enlarging. If this gets any worse, I'll need to try on some training bras!

—Michael Dorso, Seeds of Hope

• Impotence: Difficulty with erections occurs in almost all men on hormone therapy, especially men who have undergone orchiec-tomy or are taking LHRH blockers. Impotence occurs somewhat less frequently in men taking antiandrogens, particularly in the initial months of treatment, since these men continue to produce testosterone.

• Decreased libido: Following surgical and radiation treatments for prostate cancer, erections are frequently impaired because of damage to nerves, arteries, and veins, but the libido remains intact. Following hormone therapy, however, both erections and libido are affected. In the first instance, men may be impotent and care; in the second, they may be impotent and not care.

• Osteoporosis: This is one of the most serious side effects of hormone treatment, and its incidence increases with time. Studies have shown that men on hormone therapy lose 8 to 10 percent of their bone mass in the first two years of treatment, then approximately 2 percent per year thereafter. Consequently, 20 percent of men on long-term hormone treatment experience a bone fracture within five years.3 This risk can be minimized by regular exercise, calcium, and vitamin D supplementation. Medications called biphosphonates can offset the effects of hormone therapy and rebuild bones; the best-studied drugs are pamidronate (Aredia), alendronate (Fosamax), and zoledronic acid (Zometa). In 2006, however, reports linked these drugs to serious problems in the jawbone. Men who will be taking hormone therapy for several years should have a baseline bone mineral density scan.

Lost Libido

Some changes have not been so subtle. It's been at least six months since Sherry and I were able to have sexual intercourse. It's as if the wires from my brain to my penis have been disconnected. Come to think of it, that's exactly what has happened! I embrace my wife, and nothing stirs in my loins. Fortunately, I've had a concomitant loss of libido, so I don't seem to miss the sex too much.

—Michael Dorso, Seeds of Hope

• Fatigue: Approximately half of men taking hormone treatments experience fatigue and weakness. The cause may be a loss of muscle mass or anemia, both of which may be side effects of the treatment. Regular exercise can help, and anemia should be treated if it occurs.

• Mental changes: Some men on hormone treatment experience increased moodiness. Depression has been frequently reported, but it is unclear whether it is attributable to the hormones, the side effects of the hormones, or the cancer itself. Earlier studies suggested that men on hormone treatment have problems with their memory, but a 2003 study found that, contrary to what was expected, the memories of the men on hormones significantly improved.4

• Worsening of symptoms: When LHRH analog drugs are first started, they produce a brief outpouring of testosterone that may temporarily worsen the prostate cancer symptoms. This sequence can be especially problematic if the cancer has already spread to the bones. The temporary worsening of symptoms is called a flair; it can be blocked by giving an antiandrogen for at least one week prior to the first injection of the LHRH analog.

Other side effects of hormone treatments may include weight gain, elevation of cholesterol, diarrhea (with flutamide), and impairment of night vision (with nilutamide). In addition, hormone treatments affect the PSA level, causing it to become less useful as a measure of recurrence of the cancer.

Benefits of Hormone Treatment

The [hormone] treatment had one unexpected benefit: it improved my driving. No kidding! It made me less aggressive, which is one of the accidental blessings of the whole thing. I don't know if it was the hormonal therapy, or just facing my mortality, but I found myself less judgmental than I used to be.

—Don, in David Bostwick et al., Prostate Cancer

OUTCOME

Despite the significant side effects of hormone treatment, it can be effective in treating prostate cancer. For men with metastatic disease where the cancer has spread to other sites, hormone therapy may improve both the quality and quantity of their lives (see Chapter 11). For men with intermediate and advanced grades where the cancer has spread locally or is at high risk of doing so, hormone treatment in conjunction with radiation is proving to be highly effective.

The benefits of hormone therapy show up in a study carried out by the European Organization for Research and Treatment of Cancer (EORTC). A total of 415 men with prostate cancer were randomly assigned to be treated either by beam therapy alone or by beam therapy plus three years of hormone treatment with an LHRH agonist. Only 11 percent of the men had early stages of cancer; the remainder had intermediate or advanced stages, many with local extension of the cancer outside the prostate but without distant spread. At a follow-up period 5.5 years later, men treated with the combination of beam plus hormone had less evidence of clinical disease (26 percent versus 60 percent), less evidence of distant metastases (10 percent versus 29 percent), and fewer deaths due to prostate cancer (12 versus 42) than men treated by beam therapy alone.5

A similar study was carried out by the Radiation Therapy Oncology Group (RTOG), a consortium of U.S. cancer treatment centers. A total of 945 men, all of whom had prostate cancer that had spread locally, were randomly assigned to receive either beam therapy alone or beam therapy plus an LHRH agonist that was started during the last week of radiation and continued indefinitely. At the end of six years, men treated with the combined therapy had fewer distant metastases (27 percent versus 37 percent) and fewer deaths from their cancer (65 versus 80). Other RTOG studies have demonstrated that a combination of radiation plus hormone therapy is more effective than radiation alone for men with very large prostate cancers and for those with Gleason scores of 8 to 10. Still another U.S. study reported that radiation plus hormone therapy, compared to radiation alone, benefited men with a Gleason score of 7 or more and a PSA of at least 10.6

It seems established, therefore, that adjuvant hormone therapy, when given with radiation beam therapy, improves the outcome in some men with intermediate and advanced stages of prostate cancer. The optimal type and duration of hormone treatment and the dose of radiation are still being debated; several ongoing trials are attempting to answer these questions.

It is less clearly established, however, that adjuvant hormone therapy is useful for men with earlier stages of prostate cancer. Nine ongoing studies that combine hormone treatment with radical prostatectomy, radiation, or watchful waiting are trying to resolve this issue. The largest of these, the Bicalutamide Early Prostate Cancer Study, is following 8,113 men in North America, Europe, Israel, Australia, and Mexico; its preliminary findings suggest that hormone therapy may be useful in this group.7 If any benefit is demonstrated, it will have to be carefully weighed against the side effects of taking hormones.

When hormone therapy has been given to men with prostate cancer prior to surgery, it has not shown any benefit.8 Many surgeons, in fact, note that hormone treatment prior to surgery can distort normal anatomical landmarks and makes the surgery more difficult.

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