Androgen Deprivation Therapy (ADT) is a common and effective treatment for prostate cancer, where cell growth is frequently driven by male hormones, collectively known as androgens. ADT works by reducing hormone levels or by blocking their ability to interact with cancer cells. This systemic therapy slows the progression of the disease, shrinks tumors, and helps control the cancer. ADT is often referred to as hormone therapy because it suppresses the activity of these sex hormones.
The Mechanism of Hormone Deprivation
Prostate cancer cells rely heavily on androgens, primarily testosterone, to stimulate their growth and division. Testosterone binds to androgen receptors inside the cancer cells, activating genes that promote survival and proliferation. Most testosterone is produced in the testicles, with smaller amounts coming from the adrenal glands and the cancer cells themselves. Interrupting this supply chain or blocking the receptor is the fundamental goal of ADT.
ADT achieves “medical castration,” dramatically lowering circulating testosterone concentration to levels similar to those seen after surgical removal of the testicles. This deprivation starves the cancer cells of the growth signal, causing them to die or stop dividing. Although the cancer may eventually evolve to grow despite low androgen levels, this initial suppression remains a powerful therapeutic tool.
Different Forms of ADT Treatment
The clinical goal of androgen deprivation is achieved through several distinct medical and surgical methods. Medical castration uses injectable drugs that interfere with hormonal signals originating in the brain. Luteinizing Hormone-Releasing Hormone (LHRH) agonists initially cause a temporary surge in testosterone before permanently desensitizing the pituitary gland’s receptors, leading to a sustained drop in hormone production. This initial surge is sometimes managed with a short course of oral anti-androgens.
LHRH antagonists, a newer class of injectable medications, immediately block LHRH receptors in the pituitary gland. This direct blockade causes a rapid and sustained reduction in testosterone without the initial hormone surge seen with agonists, which is an advantage for men with severe disease. Both agonists and antagonists are administered as injections or implants every few weeks or months, stopping the testicles from producing the majority of testosterone.
Oral medications, known as anti-androgens, block the androgen receptor on the surface of cancer cells, preventing residual androgens from binding and delivering growth signals. Newer generation oral medications can also inhibit androgen production outside the testicles, such as in the adrenal glands, providing deeper suppression. Surgical castration, or bilateral orchiectomy, involves the permanent removal of both testicles to eliminate the primary source of testosterone production.
Clinical Roles in Prostate Cancer Care
ADT is used in a variety of clinical scenarios, ranging from treating advanced disease to supporting localized treatments. The most common application is as a primary systemic therapy for men with advanced or metastatic prostate cancer. In this setting, ADT is used to control the cancer’s growth, manage symptoms, and extend survival.
ADT is frequently prescribed as an adjuvant therapy alongside radiation therapy for men with localized but high-risk disease. Hormone suppression enhances the effectiveness of the radiation by making cancer cells more susceptible to damage. In this combined approach, ADT is typically given for a defined period, ranging from a few months to a few years, depending on the cancer’s risk level.
A third use is neoadjuvant therapy, where ADT is administered for a short time before a planned definitive treatment like prostatectomy surgery or radiation. The goal is to shrink the prostate tumor and potentially treat microscopic spread outside the gland before the main procedure. This can improve the chance of achieving clear surgical margins or enhance the effectiveness of subsequent radiation.
ADT is also considered for men who experience a biochemical recurrence, indicated by a rise in Prostate-Specific Antigen (PSA) levels after initial treatment.
Living with ADT and Managing Side Effects
The suppression of androgens, while effective against cancer, results in a range of side effects. Common physical effects include hot flashes (sudden feelings of warmth and sweating) and profound fatigue that limits daily activities. The reduction in testosterone also leads to a loss of libido and contributes to erectile dysfunction.
Metabolic changes are a concern with long-term ADT, as the loss of androgens alters body composition. Men often experience an increase in body fat and a decrease in muscle mass and strength. This shift can lead to or worsen insulin resistance, raising the risk for developing diabetes and cardiovascular events. Furthermore, testosterone suppression accelerates the loss of bone mineral density, increasing the risk of osteoporosis and bone fractures.
Many of these side effects can be mitigated through proactive management strategies:
- Regular physical activity, including aerobic exercise and resistance training, is recommended to combat fatigue, preserve muscle mass, and protect bone density.
- Physicians often recommend monitoring bone health with a DEXA scan.
- Calcium and vitamin D supplements, or sometimes bone-strengthening medications, may be prescribed.
- Lifestyle adjustments, including a balanced diet and close monitoring of cardiovascular risk factors like blood pressure and cholesterol, are important.