Androgen deprivation therapy, also known as hormonal therapy, is commonly used at various stages of prostate cancer treatment. It is usually administered in the form of medications (e.g., luteinizing hormone-releasing hormone [LHRH] analogues or agonists) that inhibit the production of testosterone — this is called chemical or medical castration. In some cases, androgen deprivation can also be performed by removing both testicles (surgical castration). Whatever the approach chosen, the objective of androgen deprivation therapy is to abolish blood-circulating levels of testosterone, which feeds prostate tumours.
Alongside its proven benefits for prostate cancer, hormonal therapy is associated with a spectrum of secondary effects; the lack of testosterone and the resulting changes in physiological functions that depend on this hormone often have a negative impact on quality of life. This article focuses on management of side effects secondary to the use of androgen deprivation therapy in general (another class of drugs used during hormonal therapy is known as antiandrogens, but these medications are not often used alone). While these side effects can be distressing, knowing what they’re up against when they start hormonal treatment can help men — and their partners — be better prepared to deal with them.
Sexual symptoms
Most men who are sexually active prior to treatment will develop sexual dysfunction once they start hormonal therapy. Even if the erectile dysfunction is not complete, the accompanying loss of libido (sexual desire) will negatively affect one’s sexual life. This is a direct consequence of the lack of testosterone, and only the recovery of usual testosterone levels will normalize sexual ability. In clinical practice, we are often asked if the use of oral medications for erectile dysfunction (e.g. Cialis®, Levitra®, Viagra®) can solve the problems induced by hormonal therapy. Unfortunately, these drugs are not extremely helpful, since the presence of circulating testosterone is crucial for a normal sexual life. The management of this secondary effect usually involves psychological preparation to help patients and their partners adapt to this change during treatment. If necessary, counselling with sex therapists can be a valuable aid. Once a temporary course of hormonal therapy is finished, testosterone levels are likely to return to normal and regaining erectile function is possible, although the time it takes can vary. Recovery can sometimes be delayed and incomplete, depending on important factors such as: the length of time one is on hormonal therapy, the patient’s age, other therapies being used, and pretreatment testosterone levels.
Hot flashes
Approximately 80% to 90% of men undergoing hormonal therapy will experience hot flashes, usually described as a feeling of intense heat that begins in the face or face and chest. The sensation may spread to the whole body and be associated with sweating, accelerated heartbeat and, sometimes, nausea. Hot flashes can last from two to 30 minutes and may recur constantly throughout the day and night. Their intensity varies from mild to severe. Hot flashes can cause insomnia, affect mood and impair concentration. There is no “standard” therapy for reducing the intensity of hot flashes, but several drugs have been studied that provide a wide range of responses. Medications that can be helpful in some cases include megestrol acetate, transdermal estrogen, gabapentin, and selective serotonin uptake inhibitors (a type of antidepressant); these are available only by prescription from your doctor. Some natural products are also reported to improve this side effect, for example soy products, vitamin E and herbal remedies, but their true effect is variable and not tested in prospective randomized trials. Also, it is suggested that people who suffer from hot flashes avoid potential triggers such as caffeine, hot drinks and spicy foods. Of course, this is very personal, as these triggers do not all have the same effect on all patients who are taking hormonal therapy.
Osteoporosis
The risk of osteoporosis and consequent bone fractures increases with prolonged androgen deprivation therapy. This happens because hormonal therapy generally decreases bone density, and weaker bones are at higher risk for fractures. This is a situation in which the best “treatment” option is prevention: Lifestyle changes, including smoking cessation, exercising (especially resistance exercises such as weight training), calcium and vitamin D supplementation, and limiting caffeine and alcohol consumption are beneficial to reduce or slow down the risk of developing osteoporosis. A new class of drugs known as bisphosphonates increase bone density and, therefore, have the potential to lower the risk of osteoporosis and fractures associated with prolonged hormonal therapy. However, the ideal timing for starting these drugs, as well as the optimal dose and schedules are still a subject of controversy; ongoing clinical trials are targeting these questions.
Body and metabolic changes
Gynecomastia, the abnormal enlargement of mammary glands (breasts) in men, is usually associated with the use of antiandrogens given as monotherapy. Although generally linked with the psychological burden of changes in body image, it may sometimes be accompanied by breast tenderness. Medical interventions to treat gynecomastia include radiation therapy, surgery or use of medications such as tamoxifen or aromatase inhibitors.
A certain percentage of patients undergoing hormonal therapy notice other less common — but not irrelevant — secondary effects, including: diabetes, cardiovascular (heart) disease, metabolic changes (especially related to fat metabolism, with changes in body composition and weight gain), and fatigue.
Find your healthy balance
It’s important to remember that any type of therapy has to be oriented and/or followed by your treating physician, and the options described above may not be suitable in all cases.
While there is no known “magic pill” to cure these symptoms, a healthy lifestyle with a well balanced diet and regular exercise and, of course, close follow-up with your physician (especially if you already have elevated cholesterol, high blood pressure or diabetes) are critical to keeping your system well balanced and helping you go through hormonal therapy with no major complications.
Dr. Fabio Cury is an Assistant Professor in the Department of Oncology, Division of Radiation Oncology, at McGill University in Montreal (Québec).
