What are some of the side effects of hormonal therapy and how are they treated?

LHRH analogues and antagonists have side effects that may affect your quality of life over the short and long term (Table 9). Some of the side effects related to these medications, such as hot flashes, erectile dysfunction, anemia, and osteoporosis, can be treated. Erectile dysfunction occurs in about 80% of men taking LHRH analogues and antagonists and is associated with decreased libido (sexual desire). The widely prescribed drug sildenafil (Viagra) as well as the other oral therapies for erectile dysfunction, vardenafil (Levitra) and tadalafil (Cialis) are effective in most of these men if they had normal erectile function before starting hormone therapy. Unfortunately, there is no medication to restore libido.

A recent Gallup survey of American men revealed that most men believe that osteoporosis is "a woman's disease." Osteoporosis^[1] is loss of bone density, and it leads to weakened bones that break more easily. Yet this disease can affect men, particularly men taking hormone therapy for prostate cancer. It is anticipated that there will be approximately 2,000 osteoporosis-induced fractures in men with advanced prostate cancer.

How can you tell if you have osteoporosis? The best way to check the bone mineral density is the dual-energy x-ray absorptiometry (DEXA) scan, the same study used to evaluate for osteoporosis in women. It is noninvasive, precise, and a quick test involving minimal radiation exposure. The test measures the bone mineral density, which is compared with values obtained from normal, young, adult control subjects.

Several factors contribute to loss of bone mineral density, but decreased sex hormone production has the most significant impact on bone mineral density. Low testosterone levels affect bone mineral density in men almost the same as low estrogen levels in women. The use of androgen deprivation therapy, whether it is via orchiectomy or LHRH analogue or LHRH antagonist with or without antiandrogen, causes decreased bone mineral density. There is an average loss of 4% per year for the first 2 years on hormone therapy and 2% per year after year 4, which is similar to the loss in women after removal of the ovaries or natural menopause. This loss of bone mineral density in men taking hormone therapy occurs for at least ten years and probably accounts for the increased incidence of fractures: 5 to 13.5% of men taking hormone therapy have fractures compared to 1% in men with prostate cancer who are not receiving hormone therapy.

Lifestyle modifications that may help decrease the risks of bone complications in men on hormonal therapy include smoking cessation, decreased alcohol intake, performing weight bearing and arm exercises, and taking supplements of 1200 mg of calcium and 400 to 800 international units of vitamin D daily. Calcium rich diets include dairy products, salmon, spinach, and tofu.

When should men on hormone therapy be evaluated for osteoporosis? There are no good guidelines to help determine how frequently DEXA scans should be obtained in men with prostate cancer who are taking hormone therapy. It may be helpful to obtain a baseline DEXA scan before starting hormone therapy and then obtain periodic DEXA scans thereafter. There are things that can be done to prevent or treat osteoporosis. Several studies have shown that an increase in bone mineral density loss occurs in men who have had an orchiectomy compared to men who are receiving LHRH analogues. The reason for this is not clear, but this result suggests that other

It may be helpful to obtain a baseline DEXA scan before starting hormone therapy and then obtain periodic DEXA scans thereafter.

chemicals are produced by the testes that may be important in maintaining bone density. Further studies may help identify these chemicals. Certain factors can put one at increased risk for osteoporosis, including sedentary lifestyle, decreased sun exposure, glucocorticoid therapy, excess caffeine intake, decreased dietary calcium and vitamin D intake or exposure, increased salt intake, aluminum-containing antacid consumption, alcohol abuse, and smoking.

Changes in lifestyle can help prevent osteoporosis. Various medications have been used in women with osteoporosis, but no treatments have been approved by the United States Food and Drug Administration (FDA) for men taking hormone therapy.

A group of medications commonly used in women with osteoporosis are the biphosphonates, which prevent bone breakdown. Three different biphosphonates, aledronate (Fosamax), neridronate (Nerexia), and zoledronate (Zometa) have been used to prevent osteoporosis in androgen-deficient men with prostate cancer. Zoledronate has been shown to increase bone density in men on hormonal therapy. Intermittent administration of either intravenous pamidronate or zoledronic acid prevents treatment-related bone loss in men with prostate cancer. In a clinical study, zoledronic acid (4 mg intravenous every 3 months) prevented bone loss and actually increased bone marrow density, during androgen-deprivation therapy for prostate cancer. Side effects of intravenous biphosphonates include an influenza-like illness (14-15%), hot flashes (23-58%), fatigue (10-38%), arthralgias (13-22%) and fever (10-11.5%). Osteonecrosis of the jaw (ONJ) has been reported in cancer patients receiving complex treatment regimens, including radiation therapy, chemotherapy, and/or corticosteroids, along with an intravenous biphosphonate. ONJ has been reported more frequently in patients with cancer types other than prostate cancer. Cancer patients undergoing invasive dental procedures (i.e. tooth extraction) are at greater risk of developing ONJ.

Another way of decreasing the risk of osteoporosis is the use of intermittent hormone therapy. With this form of therapy, you are on and off the hormones for set periods of time. The idea of intermittent hormone therapy is that the prostate cancer cells that survive while you are on hormone therapy (hormone insensitive) become hormone sensitive again when they are exposed to androgens. Possible advantages of intermittent androgen suppression include preservation of androgen sensitivity of the tumor, possible prolonged survival, improved quality of life because of recovery of libido and potency and improved sense of well-being, decrease in treatment costs, increased sensitivity of the prostate cancer to chemotherapy, and the fact that it can be used to treat all stages of prostate cancer. Intermittent hormone therapy appears to affect bone mineral density loss at six years.

• [1] The reduction in the amount of bone mass, leading to fractures after minimal trauma.