Androgen Deprivation Therapy (ADT) is a hormone therapy used in cancer treatment. It aims to reduce the influence of male hormones, known as androgens, in the body. This approach helps to slow or stop the growth of certain cancers that rely on these hormones for their development.
Targeting Hormones in Cancer
Certain cancers, particularly those affecting male reproductive organs, can depend on male hormones for their growth. Androgens, such as testosterone, act as fuel for these hormone-sensitive cancer cells. These hormones bind to specific receptors on the cancer cells, signaling them to grow and divide.
ADT works by reducing the body’s production of androgens or by blocking their ability to interact with cancer cells. This deprivation starves cancer cells of the hormones needed. By disrupting this hormonal pathway, ADT can slow cancer progression or even cause cancer cells to shrink.
Conditions Treated with ADT
Androgen Deprivation Therapy is most commonly used for prostate cancer. Prostate cancer cells frequently possess androgen receptors, and their growth is stimulated by male hormones like testosterone. Reducing these hormone levels can effectively manage the disease.
ADT is employed at various stages of prostate cancer, including advanced or metastatic cases where the cancer has spread beyond the prostate. It can also be used in conjunction with other treatments for localized or locally advanced prostate cancer. While research explores its potential in other hormone-sensitive cancers, its primary application remains prostate cancer.
Approaches to Androgen Deprivation
ADT can be achieved through surgical or medical means. Surgical approaches involve orchiectomy, the removal of the testicles, which are the primary source of testosterone production. This procedure provides an immediate and sustained reduction in androgen levels.
Medical approaches use various drug classes. Gonadotropin-Releasing Hormone (GnRH) agonists, such as leuprolide, goserelin, and triptorelin, initially cause a temporary testosterone surge. They then lead to a sustained decrease by desensitizing the pituitary gland, preventing testosterone production in the testicles.
GnRH antagonists, including degarelix and relugolix, directly block GnRH receptors in the pituitary gland. This rapidly suppresses testosterone-stimulating hormones, avoiding the initial surge. Antiandrogens, like bicalutamide, enzalutamide, apalutamide, and darolutamide, block androgen receptors on cancer cells. This prevents androgens from binding and promoting cancer growth, even if some hormones are still present.
Navigating Treatment Side Effects
The reduction of male hormones during ADT can lead to various side effects. Physical effects commonly include hot flashes, fatigue, and changes in body composition. Patients may experience decreased muscle mass, increased body fat, and weight gain.
Bone health can also be affected, leading to bone thinning or osteoporosis, which increases fracture risk. Sexual dysfunction is frequently reported, manifesting as reduced interest in sex and erectile difficulties. Additionally, some individuals may experience anemia.
Beyond physical changes, ADT can influence emotional and cognitive well-being. Mood changes, including depression and anxiety, memory issues, and difficulty concentrating, may occur. Patients should discuss any side effects with their healthcare team, as many are manageable through supportive therapies and lifestyle adjustments.
When ADT Becomes Less Effective
While ADT is initially effective for many patients, prostate cancer cells can eventually adapt and continue to grow even in very low androgen environments. This phenomenon is known as ADT resistance, leading to a condition called castration-resistant prostate cancer (CRPC). Cancer cells find ways to bypass androgen deprivation, sometimes by producing their own androgens or by altering the androgen receptor to become more sensitive to existing low levels of hormones.
When this resistance develops, the cancer progresses despite ongoing ADT. This indicates the initial hormonal strategy is no longer sufficient. At this stage, other treatment options become necessary to address the evolving cancer.