Androgen Deprivation Therapy (ADT) is a hormonal treatment that manages prostate cancer by reducing male hormones, known as androgens. Prostate cancer cells require these hormones, primarily testosterone, to grow and divide. ADT works by either stopping the body from producing androgens or by blocking their ability to act on cancer cells. This approach is a common strategy used to treat prostate cancer, particularly in advanced or high-risk cases.
How Androgens Fuel Cancer Growth
Prostate cancer cells are hormone-sensitive, meaning their survival and proliferation depend on androgens, primarily testosterone and dihydrotestosterone (DHT). These hormones are mostly produced by the testicles, with a small amount coming from the adrenal glands.
The mechanism relies on the androgen receptor (AR) within the cancer cells. Androgens circulate in the bloodstream and act like a chemical “key” that fits into the AR “lock.” Once bound, this complex moves into the cell’s nucleus and attaches to the cell’s DNA.
This binding process activates specific genes that promote cell division and growth. The goal of ADT is to block this key to halt the cancer’s growth signals.
Types of Androgen Deprivation Therapy
ADT can be achieved through surgical intervention or medical/pharmacological treatments. The goal is to lower circulating testosterone to a very low, “castrate” level. The choice depends on patient preference, logistics, and the specific clinical situation.
Surgical Deprivation
Surgical castration involves a bilateral orchiectomy, the removal of both testicles. This procedure is the most immediate and permanent way to achieve androgen deprivation since the testicles are the main source of testosterone. Orchiectomy provides a rapid and sustained reduction in testosterone levels, making it a simple and cost-effective option. However, its permanence means it is less commonly chosen than medical options.
Medical/Pharmacological Deprivation
Medical castration uses various drug classes to suppress androgen production or block their action.
LHRH Agonists
Luteinizing Hormone-Releasing Hormone (LHRH) Agonists, such as leuprolide (Lupron) or goserelin (Zoladex), are administered by injection. These drugs initially cause a temporary surge, or “flare,” in testosterone production before shutting down the signaling pathway. The flare occurs because the agonist over-stimulates the pituitary gland before desensitization stops testosterone synthesis.
LHRH Antagonists
LHRH Antagonists, such as degarelix (Firmagon), block the LHRH receptor immediately. This prevents the release of hormones that signal the testicles to produce testosterone. Avoiding the initial testosterone surge benefits patients with extensive disease where a flare could worsen symptoms.
Anti-androgens
Anti-androgens, like bicalutamide (Casodex), are oral medications that directly compete with testosterone and DHT for binding to the androgen receptor. They occupy the receptor site, preventing natural androgens from triggering the cancer growth signal. Anti-androgens are often used in combination with LHRH agonists or antagonists to achieve a more complete blockade.
Common Physical and Emotional Effects
The suppression of androgens leads to side effects mirroring low testosterone levels. One common physical manifestation is hot flashes, which are vasomotor symptoms resulting from the body adjusting to the absence of testosterone.
Sexual health is significantly impacted, with most men experiencing a substantial decrease in libido and erectile dysfunction. Because testosterone regulates sexual drive and function, its suppression reduces both desire and physical ability. Patients also frequently report profound fatigue and a noticeable loss of muscle mass, often contributing to weight gain and changes in body composition.
A long-term concern is the potential for bone density loss, leading to osteoporosis and an increased risk of fractures. Testosterone maintains bone strength, and its prolonged absence shifts the balance toward bone breakdown. Regular monitoring and preventative measures are implemented to mitigate this skeletal risk.
Metabolic and cardiovascular health can also be affected, with some men experiencing changes in cholesterol, blood sugar levels, and an increased risk of developing diabetes or heart disease. The emotional toll of ADT can include mood swings, irritability, and depression, linked to the hormonal changes and the overall impact of treatment.
Addressing Treatment Resistance
While ADT is initially effective, prostate cancer can eventually adapt to the low-androgen environment and begin growing again. This progression is termed Castration-Resistant Prostate Cancer (CRPC), meaning the cancer grows despite testosterone levels being suppressed. CRPC indicates the tumor has found new ways to utilize or produce androgens, or has bypassed the need for them.
The development of CRPC necessitates a change in treatment strategy, often involving more potent, second-generation hormonal therapies. Drugs like abiraterone (Zytiga) block an enzyme necessary for androgen synthesis in the adrenal glands and tumor cells, reducing available androgen. Another option is enzalutamide (Xtandi), a stronger anti-androgen that blocks the receptor and interferes with its ability to move into the cell nucleus.
When the cancer continues to advance, other systemic treatments are introduced. Chemotherapy agents, such as docetaxel (Taxotaxel) or cabazitaxel (Jevtana), may be used to kill rapidly dividing cancer cells. Radiopharmaceuticals and other targeted therapies manage metastatic disease.