How Hormone Therapy Halts Cancer Growth
- Hormone therapy, also known as androgen deprivation therapy (ADT), is the foundation of treatment for advanced prostate cancer. The treatment approach works by reducing or blocking testosterone, which fuels cancer growth.
- “For advanced prostate cancer … the first thing we need to do is to eliminate the source of growth for the prostate cancer and the way we do that is by eliminating the testosterone from a man’s body,” Dr. Janaki Sharma, a medical oncologist at the University of Miami, explains.
- Medications include GnRH agonists and antagonists, androgen receptor antagonists, and CYP17 inhibitors. Each drug has specific mechanisms and uses.
- Over time, prostate cancer cells can adapt. They may acquire the ability to grow and divide even in a low-testosterone environment. This stage of the disease is known as castration-resistant prostate cancer (CRPC). Despite the name, hormone therapy remains relevant and effective in managing this phase, often in combination with additional agents that further target androgen signaling.
Medications include:
- GnRH agonists and antagonists
- Androgen receptor antagonists
- CYP17 inhibitors
Hormone Therapy: The Foundation Of Systemic Treatment For Advanced Prostate Cancer
Prostate cancer remains one of the most common cancers in men worldwide. For men diagnosed with advanced or metastatic prostate cancer, hormone therapy has long been a mainstay of treatment. For decades, it has been known that reducing testosterone levels in men with prostate cancer can slow progression. In the past, this was accomplished through surgical castration (removal of the testicles) or estrogen. Today, medical castration is the standard of care, and this is commonly referred to as Androgen Deprivation Therapy (ADT).
Testosterone is a male sex hormone that plays a critical role in the development and maintenance of male reproductive tissues, muscle mass, bone density, and red blood cell production. However, in the context of prostate cancer, it acts as a potent growth factor. Prostate cancer cells are typically dependent on androgens (male hormones like testosterone) for survival and proliferation. By reducing the amount of testosterone or by blocking its activity at the receptor level, we can starve the cancer cells and slow their growth or even cause them to shrink.
Hormone Therapy & Beyond
Today, most patients are treated with medical castration, achieved through medications that either suppress the production of testosterone or block its effects. These treatments are less invasive, reversible, and often more acceptable to patients. Androgen deprivation therapy (ADT) forms the backbone of systemic treatment for advanced prostate cancer.
However, it is important to note that over time, prostate cancer cells can adapt. They may acquire the ability to grow and divide even in a low-testosterone environment. This stage of the disease is known as castration-resistant prostate cancer (CRPC). Despite the name, hormone therapy remains relevant and effective in managing this phase, often in combination with additional agents that further target androgen signaling.
The main classes of hormone therapy, specific medications used, and the side effects associated with them are discussed below.
Gonadotropin-Releasing Hormone (GnRH) Agonists and Antagonists
These drugs target the hypothalamic-pituitary-gonadal axis, effectively reducing testosterone production by the testicles.
GnRH agonists initially stimulate a surge in luteinizing hormone (LH), which leads to a temporary spike in testosterone levels — a phenomenon known as a testosterone flare. With continued use, however, the receptors in the pituitary gland become desensitized, leading to decreased testosterone production.
GnRH agonists include:
- Leuprolide (Lupron) – Administered via injection (monthly or every few months)
- Goserelin (Zoladex) – Delivered as an implant under the skin
Testosterone flare can worsen symptoms temporarily, especially in patients with spinal metastases or urinary obstruction, so additional medications (anti-androgens) may be prescribed during the initial weeks of therapy.
GnRH antagonists block GnRH receptors directly, causing an immediate drop in testosterone without the flare.
Options include:
- Degarelix (Firmagon) – Given via monthly injection
- Relugolix (Orgovyx) – A newer oral GnRH antagonist, which offers the convenience of pills and reduces cardiovascular side effects compared to older agents
Androgen Receptor Antagonists (AR Antagonists)
Instead of lowering testosterone levels, this class of drugs blocks the action of androgens at the receptor level within prostate cancer cells. They are particularly useful in the castration-resistant setting, often used in combination with ADT.
Options include:
- Enzalutamide (Xtandi) – An oral medication shown to improve survival in both castration-sensitive and castration-resistant disease
- Apalutamide (Erleada) – Approved for non-metastatic CRPC and metastatic castration-sensitive prostate cancer
- Darolutamide (Nubeqa) – Similar to enzalutamide but with fewer central nervous system side effects like seizures and fatigue
- Bicalutamide (Casodex) – One of the earliest androgen receptor blockers, now largely replaced by the newer agents for advanced disease
CYP17 Inhibitors
These target the androgen biosynthesis pathway, specifically the enzyme CYP17A1, which is critical for testosterone production in the adrenal glands and the tumor itself (in some cases).
Abiraterone acetate (Zytiga) is often used in combination with low-dose prednisone (a steroid) to mitigate mineralocorticoid excess caused by CYP17 inhibition.
It has demonstrated significant survival benefits in both metastatic hormone-sensitive and castration-resistant prostate cancer.
Side Effects Of Hormone Therapy
For men with prostate cancer, hormone therapy can dramatically improve outcomes, but it is not without its challenges. The side effects are largely related to low testosterone levels and can significantly impact quality of life.
Potential side effects include:
- Hot Flashes
- Loss of Libido and Erectile Dysfunction
- Fatigue and Decreased Energy Levels
- Weight Gain and Loss of Muscle Mass
- Bone Thinning (Osteopenia/Osteoporosis)
- Mood Changes and Depression
- Cardiovascular Risks
While side effects can be difficult, it’s important for patients to know that there is a huge range of medications and interventions their medical team can provide to help address and alleviate some of these issues.
“Some of the techniques we use to help patients avoid fatigue are to encourage increased exercise, which stimulates positive endorphin release and can help with the fatigue,” Dr. Sharma shares as an example.
“However, it’s challenging to explain that even though you’re feeling incredibly tired from treatment, you need to be doing more exercise. So while I completely understand that urge, it is important to move — even 15 to 20 minutes — just to try and relieve some of the fatigue. This can also help with some of the joint pains or hot flashes that are associated with some of these treatments.”
Questions To Ask Your Doctor
- Will hormone therapy be part of my treatment plan?
- How long will I have to be on hormone therapy?
- What are my options if side effects are a challenge?
- What if my cancer stops responding?
- If hormone therapy is an option, how can I decide which one is best for me?
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