Androgen Deprivation Therapy (ADT) is a hormonal treatment that reduces the levels of male hormones, known as androgens, in the body. This approach is primarily used in the management of certain hormone-sensitive cancers. By decreasing the availability of these hormones, ADT slows or stops the growth of cancer cells that rely on androgens for their proliferation.
The Role of Androgens in the Body
Androgens are a group of sex hormones that play a role in developing male physical characteristics and maintaining overall health. Testosterone is the primary androgen, produced mainly in the testicles, with smaller amounts from the adrenal glands. These hormones contribute to a deep voice, hair growth, sperm development, bone density, muscle development, and sexual desire.
However, in certain cancers, particularly prostate cancer, androgens can fuel tumor growth. Prostate cancer cells often possess androgen receptors. When androgens bind to these receptors, they stimulate cancer cells to grow and multiply. This dependency makes targeting androgens an effective strategy to control prostate cancer progression.
How Androgen Deprivation Therapy Works
ADT works by reducing androgen levels in the body or by blocking their ability to stimulate cancer cells. There are two main approaches: surgical castration and medical castration. Surgical castration, known as bilateral orchiectomy, involves removing the testicles, the primary source of testosterone production. This procedure results in a rapid drop in androgen levels.
Medical castration uses various drugs to achieve a similar effect without surgery. These include:
LHRH (GnRH) agonists: Such as leuprolide, goserelin, and triptorelin. These initially cause a temporary testosterone surge before a sustained decrease. They work by overstimulating and then desensitizing the pituitary gland’s GnRH receptors, which ultimately suppresses the release of hormones that signal the testicles to produce testosterone.
GnRH antagonists: Such as degarelix. These directly block GnRH receptors in the pituitary gland, leading to a rapid reduction in testosterone levels without the initial “flare” effect seen with GnRH agonists.
Anti-androgens: Like bicalutamide. These work by blocking androgen receptors on prostate cancer cells, preventing androgens from binding and stimulating tumor growth.
Androgen synthesis inhibitors: Such as abiraterone. These block the CYP17A1 enzyme involved in androgen production in the adrenal glands and tumor tissue.
Androgen receptor inhibitors: Such as enzalutamide. These go beyond simply blocking receptor binding; they also inhibit the movement of androgen receptors into the cell nucleus and their interaction with DNA, further disrupting cancer cell growth.
When Androgen Deprivation Therapy Is Used
ADT is a widely used treatment for prostate cancer across various stages. For men with advanced or metastatic prostate cancer, ADT is often a primary treatment to slow progression and alleviate symptoms. It can reduce tumor size and lower prostate-specific antigen (PSA) levels, which are markers for prostate cancer activity.
The therapy is also employed with radiation therapy for individuals with high-risk localized or locally advanced prostate cancer. In these cases, ADT can be given before, during, and after radiation to enhance its effectiveness by shrinking the tumor and improving cure rates. For patients experiencing a recurrence after initial treatments like surgery or radiation, ADT can help manage the disease by controlling remaining cancer cells.
Managing Side Effects of ADT
Androgen deprivation therapy can lead to various side effects due to the reduction in male hormone levels. These include:
Hot flashes are a common occurrence, often described as sudden sensations of warmth and flushing.
Fatigue is another frequent complaint, impacting daily activities and overall energy levels.
Sexual side effects are also prevalent, including decreased libido and erectile dysfunction.
Long-term use of ADT can contribute to bone thinning, known as osteoporosis, which increases the risk of fractures.
Patients may also experience muscle loss and weight gain, often in the form of increased fat mass.
Metabolic changes, such as an increased risk of developing diabetes or cardiovascular issues, can also occur.
Management strategies for these side effects often involve lifestyle adjustments, such as regular exercise to combat muscle loss and weight gain, and maintaining a balanced diet. Medications or other interventions may be recommended to address specific symptoms like hot flashes or bone density loss.