Hormone Therapy for Prostate Cancer

Hormone therapy, or what doctors call Androgen Deprivation Therapy (ADT), is sometimes used as a treatment for men with prostate cancer. The male sex hormones are called “androgens” and the primary androgen is testosterone. The goal of ADT is to dramatically reduce the body's production of testosterone.

Testosterone is produced mainly in the testicles, although a small amount is also produced by the adrenal glands. Androgens stimulate the growth of prostate cancer cells, and therefore decreasing testosterone levels can cause prostate cancers to shrink or to grow more slowly.

Which Men with Prostate Cancer Need ADT?

Some men receive “short-term” ADT in conjunction with radiation treatment for newly diagnosed prostate cancer. Typically, “short-term” ADT is administered for 6 to 24 months. Other men whose prostate cancer has spread beyond the prostate may stay on ADT permanently.

How is Androgen Deprivation Therapy (ADT) Given?

Years ago, the only way to reduce a man's testosterone level was to surgically remove the testicles, a procedure called orchiectomy. Fortunately, today we have treatments that can achieve the same type of reduction in testosterone levels without surgery. Usually, your urologist will recommend injections of a medication designed to shut down testicular androgen production. The shots are given in your urologist's office, usually at 3 to 4 months intervals, although the exact schedule will depend on which “brand” of medication is used.

Potential Side Effects of ADT

Although ADT or hormone therapy is an effective treatment for certain men with prostate cancer, it can have side effects such as osteoporosis, hot flashes, weight gain, and changes in sexual function.

  • Osteoporosis

    Osteoporosis, which is a condition characterized by a decrease in bone mass and density, increases the risk of bone fractures. Although osteoporosis is most commonly seen in postmenopausal women, it is becoming more prevalent in men. Two million men in the U.S. now have osteoporosis, and another 12 million are considered at risk for the disease. Men treated with ADT for prostate cancer are at increased risk of osteoporosis due to the role of androgens in bone formation and breakdown. When ADT disrupts normal hormonal balance by stopping androgen production, significant bone loss can result. Loss of bone mineral density (BMD) is a serious consequence of ADT, and studies have shown that men undergoing hormone therapy have lower BMD, higher rates of osteoporosis, and higher rates of bone fractures than men of the same age who are not undergoing hormone therapy. This acceleration in bone loss appears to begin within the first six months on ADT, and the longer you are treated with hormone therapy, the higher your risk of low BMD, osteoporosis, and fractures. A recent study looked at long-term ADT, and determined that after 10 years on ADT, 81% of men had osteoporosis.

  • Hot Flashes

    Hot flashes are a common symptom during ADT. Although most men do experience them, they are usually mild and may go away with time. If the hot flashes become very bothersome, you should speak to your urologist, who may recommend medications to reduce them.

  • Weight gain

    The large drop in androgen levels can cause some men to experience weight gain during ADT. If you notice you've gained a few pounds, taking action to reduce further weight gain is important for your overall health. Significant weight gain may increase your risk of heart disease and diabetes. Working with a Registered Dietitian can help you manage your weight and develop a healthy diet.

    Increasing physical activity can also help you control your weight. Aerobic exercise will burn calories, and strength training can increase lean body mass (muscle), which in turn increases metabolism and allows your body to burn more calories throughout the day. Please see the section on Exercise and Bone Health for more information about the benefits of exercise and how to get started.

  • Changes in sexual function

    The reduction in testosterone levels during ADT may cause sexual side effects such as loss of desire or erectile dysfunction. Your urologist should be able to provide you with options for dealing with these symptoms.

Maintaining Bone Health During ADT

When you start ADT, and periodically during your treatment, your urologist may suggest a special test called a Bone Densitometry (DEXA) Scan, which will measure your bone mineral density (BMD).

There are things that you can do to keep your bones strong while undergoing hormone therapy. Studies have shown that nutritional supplementation with calcium, vitamin D, magnesium, and other trace minerals can strengthen bones. Supplementation with these nutrients, along with a healthy diet, weight-bearing exercise such as walking and resistance training, eliminating smoking, and decreased consumption of alcohol are very important for maintaining bone strength and decreasing the risk of osteoporosis.

Nutrition and Bone Health

Calcium

  • Calcium is the most abundant mineral in bone. Numerous research studies have shown the importance of adequate calcium intake for maintaining bone strength and improving bone mineral density. When blood levels of calcium are low, the body “borrows” calcium from the bones, which leads to decreases in BMD. Eating a diet rich in calcium (a variety of vegetables, nonfat or low-fat dairy, and calcium-fortified foods) is important to maintain adequate calcium levels. Because many Americans do not get enough calcium from their diet, adding a calcium supplement is important to ensure adequate daily intake.

    Several forms of calcium are used in nutritional supplements, with calcium citrate and calcium carbonate being the most common. While calcium carbonate requires food, and stomach acid, for absorption, calcium citrate can be absorbed with or without food. Calcium citrate is also absorbed by those taking acid--reducing drugs such as H2 Antagonists (Pepcid®, Zantac®, Tagamet®) or proton pump inhibitors (Aciphex®, Nexium®, Prevacid®, Prilosec®, Protonix®).

Vitamin D

  • Vitamin D is a fat-soluble vitamin that functions to maintain normal blood levels of calcium, thus helping to build and maintain strong bones. Without adequate vitamin D, bones become thin, brittle, or soft, increasing the risk of fractures and bone diseases such as osteomalacia and osteoporosis.

    In addition to its role in bone health, vitamin D promotes normal cellular growth and differentiation and is thought to decrease the risk and progression of prostate cancer. Recent research indicates that more vitamin D may be needed by men with prostate cancer due to an increase in the enzyme that breaks down vitamin D. This causes prostate cancer cells to be less sensitive to the effects of vitamin D, and thus a higher intake is needed to receive a beneficial effect.

    It is difficult to acquire optimal levels of vitamin D from diet alone, because vitamin D occurs naturally only in fatty fish, and milk is fortified with only 100 IU per cup. Our skin can make vitamin D when exposed to sunlight, although the amount varies greatly depending on age, location or latitude, time of day, smog, and use of sunscreen. It is estimated that up to 80% of Americans may be vitamin D deficient due to lack of sunlight exposure, increased sunscreen use, less efficient vitamin D production and metabolism with age, increased obesity rates, and decreased intake of vitamin D from foods.

    Research indicates that up to 10,000 IU per day should be safe for most people, and doses higher than 1,000 IU per day are essential to decrease hip fractures, prevent falls, and increase bone mineral density.

Magnesium

  • Magnesium is a mineral that is involved in over 300 essential metabolic reactions in the human body. Bone is composed of approximately 1% magnesium. As the bone loses magnesium, it becomes more brittle and prone to fracture. Magnesium has been shown to improve bone density, and magnesium deficiency can result in bone loss and osteoporosis. The richest dietary sources of magnesium are green leafy vegetables, whole grains, and nuts. Magnesium naturally occurring in food has not been shown to have any adverse effects. Magnesium supplementation up to 350 mg per day should not cause any negative effects. Higher supplemental doses may cause diarrhea and gastrointestinal side effects.

Boron

  • Boron is an element that appears to be important in bone remodeling, primarily through its interaction with magnesium, calcium, and vitamin D. Recent research supports the use of boron for the promotion of bone and joint health. Dietary boron has been shown to affect several aspects of mineral metabolism in animal studies. In humans, boron supplementation was shown to decrease calcium and magnesium loss. Boron supplementation may potentially improve bone density. Boron appears to be safe in doses up to 18 mg daily even if taken for prolonged periods of time. The average intake in the American diet is about 1 mg daily. There is some evidence that a more optimal intake of boron may be 2 to 3 mg daily. Fruits and vegetables are the most significant dietary sources of boron.

Vitamin K

  • Vitamin K is a fat-soluble vitamin that plays a role in blood clotting and bone mineralization. Studies indicate that low intakes of vitamin K are associated with low bone density and higher fracture risk. Vitamin K has been shown to be safe at high doses (up to 45 mg/day) in most adults.

    Vitamin K occurs naturally in two forms: vitamin K1 (phylloquinone) and vitamin K2 (menaquinone). Vitamin K1, which is synthesized by plants and is the main dietary source of vitamin K, is found mostly in green leafy vegetables. Vitamin K2 is synthesized by intestinal bacteria, and is also found in fermented soy products such as natto.

    For people taking Coumadin® (a blood thinner), a consistent daily intake of vitamin K is important. In patients with lower vitamin K levels, it is more difficult to stabilize INR (International Normalized Ratio) levels. Long term use of Coumadin has been associated with an increased risk of osteoporosis, which is perhaps associated with a low intake of vitamin K. Although doses of vitamin K up to 100 mcg have not resulted in a significant change in Coumadin dose in small studies, people taking Coumadin should consult with their physician about taking a supplement containing vitamin K, and should have their INR levels closely monitored.

Strontium

  • Strontium is a trace mineral that occurs naturally in small amounts in water, food, soil, and bone. Strontium is similar in structure to calcium and is absorbed in the body in small amounts. Research indicates that strontium slows bone breakdown, increases new bone formation, improves BMD, and decreases the risk of fractures. Strontium appears to be safe in doses up to approximately 700 mg per day

    Strontium is the active component of a prescription drug, strontium ranelate, which has been approved in Europe since 2004 to treat osteoporosis. In the U.S., strontium ranelate is not available, but the mineral strontium is available in smaller amounts in the form of dietary supplements.

Regular Exercise Helps Maintain Bone Health

Some of the possible side effects associated with ADT such as fatigue, weight gain, and loss of muscle, can be minimized by regular "weight bearing" and “resistance” exercise. Exercises that are weight or load-bearing include walking, weight lifting, jogging, stair-climbing, aerobics, and dancing. These exercises require muscles to work against gravity, and therefore apply stress to the bone. Research shows that when you engage in exercise that stresses the bone, it becomes stronger and denser. Weight-bearing exercise stimulates the growth of new bone. Thirty minutes of weight-bearing aerobic exercise (such as walking) on most days of the week can also improve heart health, circulation, coordination, balance, and strength.

Resistance training, or weight lifting, can have a significant bone-building effect. Increasing muscle strength causes the muscles to pull harder on the bone, which can build bone mass. A study conducted in men undergoing ADT for prostate cancer showed that a strength training program decreased fatigue, improved health-related quality of life, and increased upper and lower body muscle strength.

Stretching is also an important component of any exercise program. Stretching improves flexibility, increases joint mobility, and may decrease the risk of injury. Gentle stretches should be performed only after “warming-up” the muscles, or after exercising, during your “cool down” period. When stretching, movement should be slow and easy, with no bouncing.

Remember to check with your physician before beginning any exercise program.

Prescription Medications for Improving Bone Health During ADT

In patients who already have low BMD or osteoporosis, certain prescription medications may be prescribed in addition to diet and lifestyle changes and nutritional supplementation. Examples of these medications are bisphosphonates such as Fosamax, Actonel, and Zometa, which have been proven to improve BMD and are considered effec�tive for the prevention and treatment of osteoporosis. When taking these medications, it is still very important to take adequate amounts of calcium (1000-1200 mg/day) and vitamin D (2000 IU/day).