Men can experience a wide range of long-term treatment effects when they undergo hormone therapy, which is sometimes known as androgen deprivation therapy or ADT. ADT works to deprive the body of the male hormone (androgen) called testosterone. It is an ongoing treatment that dramatically reduces testosterone levels, so body-wide or systemic effects are to be expected.

Testosterone is the primary libido or sex drive hormone in both men and women, and it is vital for bone density, maintaining and building muscles, regulating body fat, improving the body’s use of insulin, and sustaining red blood cell counts to prevent anaemia and changes in memory, concentration, energy, and motivation. Men on ADT are also more likely to develop metabolic syndrome, which is defined as a combination of medical disorders that increases the risk of developing cardiovascular disease and diabetes.

Metabolic Syndrome: Three of these five risk factors (American Heart Association Standards) Elevated waist circumference (greater than 40 inches or 102 cm in men) Elevated triglycerides (greater or equal to 150 mg/dL or 1.7 mmol/L) Reduced good cholesterol or HDL (less than 40 mg/dL  or 1.03 mmol/L in men) High blood pressure (greater than or equal to 130/85 mm Hg) or use of medication to control hypertension Elevated fasting glucose level (greater than or equal to 100 mg/dL or 5.6 mmol/L) or use of medication for hyperglycaemia

Other possible side effects include

• Weight gain
• Loss of muscle mass
• Loss of bone density (osteoporosis or bone thinning)
• Hot flashes
• Growth of breast tissue
• Loss of libido and erectile dysfunction
• Depression
• Anaemia, lack of energy, and cognitive changes

In spite of these possible side effects, hormone therapy remains very beneficial for many men with prostate cancer, both in terms of symptomatic relief and increased survival.

Physicians agree, however, that men undergoing ADT should be fully informed of these possible side effects and monitored for them, so lifestyle changes and therapies can be suggested for their prevention or treatment.

Preventing or Managing Possible Treatment Side Effects of ADT

Metabolic Syndrome, Weight Gain, Loss of Muscle Mass
Although there are no established protocols for preventing and managing the metabolic and cardiovascular effects of ADT, it seems wise to ask your medical team to assess your risk of diabetes and cardiac problems before you undergo hormone therapy and to monitor you for increases in weight, fat body mass, fasting blood sugar levels, and cholesterol and blood pressure.

Various lifestyle changes can help men decrease their risk of experiencing metabolic syndrome, weight gain, and loss of muscle mass. These include diet and exercise.

Diet
Diets known to be heart healthy and good for diabetics may help men on ADT to regulate their blood pressure, cholesterol, and insulin levels and maintain their proper weight. These diets tend to be high in fruit and vegetables, whole-grain products, lower-fat milk products and alternatives, and lower-fat meat and alternatives. They also emphasize low glycaemic index (GI) foods, limit sweets and alcohol, and stress regular meals or snacks to help control glucose levels and keep them consistent throughout the day.

Click here for more information from PCCN on diet and prostate cancer.  Other excellent information on heart and blood sugar friendly diets is available from the Canadian Heart and Stroke Foundation and the Canadian Diabetes Association.

Exercise
For men receiving ADT, resistance training and aerobic exercise have been shown to improve muscle strength, control abdominal fat and weight-gain, and regulate blood sugar levels. In other words, exercise is a good step toward preventing metabolic syndrome. Also, if fatigue is contributing to depression, a regular exercise program can help. (See an abstract of the article “Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer.”)

Click here for more information from PCCN on exercise and prostate cancer.

Osteoporosis
The connection between ADT and an accelerated loss of bone density is now established. On average, a man on ADT will experience a 2.2 to 5.4 per cent loss of bone mineral density in the spine and a .5 to 6.5 per cent loss in the hip over the course of a year. Hormone therapy also escalates a man’s risk of fracturing a bone, and this risk increases the longer the therapy continues.

Men should have a baseline bone mineral density test before beginning hormone therapy and follow-up tests every one to two years while they are on ADT. And they should consult their physicians about their vitamin D levels and about preventing or managing osteoporosis or osteopenia (the step that precedes osteoporosis). Lifestyle recommendations to decrease the risk of developing osteoporosis include the following:

• exercise (including weight-bearing exercises such as walking or jogging, flexibility exercises such as yoga, resistance exercises such as weight training, and aerobic exercise);
• follow a diet that includes sufficient vitamin D and calcium and that allows a man to maintain a healthy weight;
• stop smoking; and
• reduce alcohol and caffeine consumption.

Doctors sometimes recommend supplements of vitamin D or calcium or treatment with bisphosphonates.

Hot Flashes
About 80 per cent of men undergoing ADT experience these sudden and transitory feelings of warmth and flushing over their faces and upper bodies. Hot flashes range from being mild but annoying to debilitating. When they are affecting a man’s quality of life, treatments are possible. Often, doctors will prescribe antidepressants (e.g., SNRIs or SSRIs) or the progestin (synthetic form of the female hormone progesterone) megestrol acetate. Some studies have found that alternative therapies such as acupuncture can help with symptom control. (Read the PCCN article “Acupuncture reduced hot flashes for men on hormone therapy.”)

Growth of Breast Tissue
Gynaecomastia (or the development of mammary glands in males resulting in breast enlargement) can occur as a side effect of hormone therapy. It is often accompanied by breast pain. Treatment options include radiation, which helps with the pain but is less effective in reducing breast size, and surgery (either mastectomy, liposuction, or some combination of both approaches).

Loss of Libido and Other Sexual Side Effects
Studies show a significant decline in sexual interest (libido) among men undergoing hormone therapy for prostate cancer. Erectile dysfunction is a common and associated problem, as is loss of ejaculation. Because testosterone is required for the production of semen, when there is a very low testosterone level, little to no semen can be produced—or ejaculated.

Most men on ADT experience a dramatic loss of libido. Dr. Mulhall explains it this way in his book Saving Your Sex Life: A Guide for Men with Prostate Cancer:


Because testosterone is the primary libido hormone and also the hormone that spurs prostate cancer growth, there are few options open for a man on ADT who experiences a declining interest in sex. Couples counselling can help, especially as research has shown that men on ADT experience a kind of “sexual neutrality,” which is also experienced by many postmenopausal women. In other words, both rarely think about sex but enjoy sex when they have it. Men on ADT and their partners, then, might just need some advice on how to increase the frequency of their sexual activity under these changed circumstances, for example, by keeping track of when they last had sex and planning for a certain frequency or by changing the person who initiates intimacy in the relationship. Discussing physical intimacy that does not involve sexual intercourse might also help couples remain close.

The significant drop of testosterone levels that occur with ADT can have negative effects on erectile tissue as well, which can lead to erectile dysfunction. Some doctors prescribe low-dose Viagra in the weeks leading up to ADT and during the course of hormone therapy, but the efficacy of this practice still needs to be tested. If the erection tissue is so damaged as to cause a venous leak (blood leaks out of the erection spaces and back into the veins of the pelvis), a man will most likely need either penile injection therapy or penile implant surgery to achieve an erection. He will not be able to recover a natural erection, and Viagra or other similar drugs will not work well. For more information, see the PCCN page on erectile dysfunction.

A less well known but possible sexual side effect of ADT is genital shrinkage (the loss of penile length and girth as well as testicular shrinkage). Cosmetic surgery is an option in this circumstance.

Depression
Testosterone also has neuropsychological effects, so low levels of the hormone can produce changes in memory, mood, and self-esteem. Changes in sexual desire and functioning, fatigue, and diminished energy probably contribute as well to the higher incidence of depression experienced by men on ADT.  Support groups, counselling, psychotherapy, antidepressants and other medications, as well as a regular exercise program and a healthy diet can help men manage depression.

Anaemia
Most men on ADT experience a drop in red blood cells of more than 10 per cent, which can cause periods of fatigue. For some men, anaemia and loss of quality of life result. These men are usually treated with injections of recombinant erythropoietin, a glycoprotein hormone that controls red blood cell production.


NOTE: Remember, hormone therapy is a proven, life-extending treatment of prostate cancer. The information provided here is not meant to discourage you from beginning hormone therapy if that is your best option but rather to inform you of the possible side effects of ADT, so you can take steps with your medical team to prevent them, if at all possible; have them treated, if they occur; or cope with them, if they cannot be avoided or treated.

References:
Shahrir Kabir, Pascal Mancuso, Prem Rashid, August 2008, “Androgen deprivation therapy: Managing side effects,” Australian Family Physician, Vol. 37, No. 8, pp. 641-645.

Heather A. Payne, Robert Laing, Robert Thomas, Bertrand Tombal, Janis Troup, March/April 2001, “Healthy lifestyle for men living with hormone therapy for prostate cancer,” Trends in Urology, pp/ 37-40.