Androgen Deprivation Therapy (ADT) is a hormone therapy used to treat prostate cancer. Its purpose is to lower the levels of male hormones, called androgens, in the body. Since prostate cancer cells rely on androgens to grow, reducing these hormones can cause tumors to shrink or grow more slowly. ADT is a standard treatment for advanced prostate cancer and is also used alongside other treatments like radiation for earlier stages of the disease. The therapy can be administered through medications or, less commonly, surgery.
The Role of Androgens in Prostate Cancer
Androgens, with testosterone being the most well-known, are male hormones responsible for developing male characteristics and for the normal growth of the prostate gland. In prostate cancer, androgens act as fuel for the cancerous cells, stimulating their growth. The hormones bind to and activate proteins in prostate cells known as androgen receptors. Once activated, these receptors signal genes that cause the prostate cells, including cancerous ones, to grow. Most androgens are produced in the testicles, with a smaller amount made by the adrenal glands, which are located above the kidneys, and some prostate cancer cells can even produce their own.
How Androgen Deprivation Therapy Works
Androgen Deprivation Therapy functions by either stopping the body from making androgens or by blocking them from reaching cancer cells. One method uses medications targeting the pituitary gland, which controls testosterone production. These drugs, known as Luteinizing Hormone-Releasing Hormone (LHRH) agonists and antagonists, halt the signal to produce testosterone in a process called medical castration. LHRH agonists, like leuprolide and goserelin, are given as injections or small implants under the skin. They cause an initial testosterone surge before levels drop, so anti-androgens may be given beforehand to prevent a “tumor flare,” while LHRH antagonists work more quickly without causing a spike.
Another approach uses anti-androgen medications, taken as daily pills. Drugs like bicalutamide, enzalutamide, and apalutamide attach to the androgen receptors on prostate cancer cells, preventing testosterone from stimulating cell growth. Anti-androgens are often used with LHRH agonists to provide a more complete hormonal blockade. In rare cases, a surgical procedure called an orchiectomy, which removes the testicles, is performed for a permanent reduction of testosterone.
Common Side Effects of ADT
Lowering androgen levels throughout the body leads to a range of side effects, as these hormones affect more than just the prostate. Side effects impact individuals differently, and their intensity often depends on the treatment’s duration. Many effects are similar to the symptoms of menopause in women, which is also caused by a sharp drop in sex hormones.
Physically, hot flashes are one of the most common side effects, affecting up to 80% of men on ADT. Other physical changes include fatigue, loss of muscle mass, and an increase in body fat, particularly around the abdomen. There is also a risk of osteoporosis, a condition where bones become weak and increase the likelihood of fractures. Some men may experience breast tissue swelling or tenderness, known as gynecomastia.
Sexual side effects are also common, occurring within the first few months of starting therapy. These include a reduced or complete loss of sexual desire (libido) and erectile dysfunction. ADT can also affect a person’s emotional and cognitive state, and men may experience mood swings, depression, or difficulty with memory and concentration. Long-term use has also been linked to an increased risk of developing diabetes, high cholesterol, and certain heart problems.
Managing Treatment and Side Effects
The effectiveness of ADT is monitored through regular blood tests measuring prostate-specific antigen (PSA) levels. A falling PSA level indicates the treatment is slowing the cancer’s growth. Regular check-ups allow doctors to track the cancer’s response and manage any side effects that arise.
Lifestyle modifications are a key component of managing ADT side effects. A healthy diet and regular exercise can help counteract weight gain, muscle loss, and fatigue. Strength-training exercises are particularly beneficial for preserving muscle and bone mass. To combat bone thinning, doctors may recommend calcium and vitamin D supplements or prescribe medications like bisphosphonates to reduce the risk of fractures.
For some men, intermittent ADT may be an option. This approach involves taking breaks from therapy once PSA levels are low and stable, and restarting treatment if PSA begins to rise again. Intermittent therapy can provide a reprieve from side effects, improving quality of life without compromising the treatment’s effectiveness for certain individuals. This method requires close monitoring and is not suitable for everyone.