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Androgen Deprivation Therapy (ADT)

Key Points

  • Androgens are hormones that promote male characteristics such as facial hair, sexual function and muscle mass. Testosterone is the main androgen.
  • Prostate cancer cells need androgens to grow.
  • Androgen deprivation therapy (ADT), a type of treatment for prostate cancer, blocks the production or effects of testosterone and other male hormones.
  • ADT is most often used to treat:
    • Cancer that has spread outside the prostate
    • Recurrence of prostate cancer after another therapy has been used
    • Men who are at high risk of experiencing cancer recurrence after surgery or radiation therapy
  • “Hormone therapy” is another name for ADT. Although these terms can be used interchangeably, Prostate Cancer Canada uses ADT (it is more specific to prostate cancer treatment).
  • This therapy affects the whole body rather than a particular area

What are androgens?

Androgens are male sex hormones.  The two most common are testosterone and dihydrotestosterone (DHT).  Women have small amounts of androgens too.  Like all hormones, androgens affect the actions of cells and tissues in the body.  Most testosterone is produced in the testicles, but a small amount is made by the adrenal glands (just above the kidneys).  Prostate cancer cells can also produce testosterone.

What do androgens and prostate cancer have to do with each other?

Androgens are needed to ensure that the prostate grows and functions normally.  Androgens can lead to prostate cancer, because they bind to and activate (turn on) the ‘androgen receptor’, a protein that is produced by the cells in the prostate gland.   Once these androgen receptors have been bound to androgen, they then stimulate certain genes that cause prostate cells to grow. 
At early stages of prostate cancer, prostate cancers “feed off” androgens, depending on them to grow.  These types of prostate cancers are known as “androgen-dependent” or “androgen-sensitive”.  Androgen Deprivation Therapy (ADT) works to ‘deprive’ these prostate cells of androgen, thus inhibiting their development.
Unfortunately in men with more advanced cancer, most prostate cancers will eventually continue to grow even when there is a low level of androgens in the body – a phenomenon known as “castration resistant prostate cancer”.


How does ADT work?

There are two methods of ADT:

  1. Surgical removal of one or both of the testicles (orchiectomy) to prevent testosterone production.  This type of treatment is radical in that is can reduce the level of testosterone by 90-95%.  Another name for this approach is “surgical castration”.  Due to its permanent and irreversible nature, it is rarely used.
  2. Medication. The main categories include:
    • Luteinizing hormone-releasing hormone (LHRH) agonists and LHRH antagonists, both of which interfere with androgen production but with somewhat different mechanisms. They are given as injections.
    • Treatment with an LHRH agonist is sometimes called “medical castration” or “chemical castration” because it lowers androgen levels in the body as much as an orchiectomy. If you are given an LHRH agonist for the first time, you may experience something known as “testosterone flare”.  This refers to a spike in the amount of testosterone in your body, caused by the LHRH agonists prompting the pituitary gland to secrete extra luteinizing hormone into the body before it blocks it from doing so.  This flare can make clinical symptoms worse, especially if you have advanced prostate cancer.  To offset this increase in testosterone, you may be given another type of hormone therapy called anti-androgen therapy, along with the LHRH agonist, during the first few weeks of treatment.
    • Treatment with an LHRH antagonist (also known as “medical castration”) works by: Stops LHRH from binding to receptors in the pituitary gland→Stops secretion of LHRH →levels of androgen fall.  Unlike the LHRH agonist, LHRH antagonist doesn’t cause a testosterone flare.
    • Anti-androgens, which block the effects of male hormones on prostate cancer and prostate-related cells by blocking the androgen receptor. These are oral pills.
    • Estrogens or female hormones. When the brain detects an abnormally high level of female hormones (usually administered as pills), it stops producing its own hormones, both male (androgens) and female (estrogens). (Estrogens are rarely used nowadays for prostate cancer due to potentially serious side effects such as strokes, blood clots, high blood pressure and fluid retention).

Other very promising new agents include Abiraterone (a drug which counter-acts the enzyme responsible for androgen production, thus stopping androgen production); and Enzalutamide (a very potent anti-androgen)  
What can I expect?
ADT is used in various ways to treat prostate cancer.
  • Combination ADT: Anti-androgens are combined with either a LHRH agonist   or surgical removal of the testicles.
  • Intermittent ADT: ADT is stopped once the PSA number is lowered and stabilized. ADT is restarted when the PSA number increases again (sometimes months, maybe years later).
ADT is used in different circumstances to treat prostate cancer:
1. “Primary treatment”: ADT is used as the single first-line treatment.  If you have early-stage prostate cancer which has an intermediate to high risk of recurrence (cancer returning), you may be offered adjuvant hormone therapy after radiation therapy or prostatectomy.  Your doctor will tell you, based on a combination of grading and staging, whether your tumour has spread into surrounding tissue, and whether or not tumour cells are found in nearby lymph nodes.  Men who have adjuvant hormone therapy after external beam radiation therapy for prostate cancer live longer, both overall and without having a recurrence, than men who are treated with radiation therapy alone (NCI, 2014).
2. Neo-adjuvant ADT: ADT is given before local treatment (either surgical prostate removal or radiotherapy).  ADT reduces the size of the tumour to make the main treatment potentially more effective.  If you have early-stage prostate cancer which has an intermediate to high risk of recurrence, you will probably receive hormone therapy before or during radiation therapy, as well as receiving hormone therapy after radiation therapy. 
3. Adjuvant ADT: Used directly after surgery or radiation “just to be safe”, in case there is a chance that cancerous cells may have remained somewhere in the body.
What are the possible side-effects and risks?
As with all treatments, ADT carries possible side-effects and risks. The following is a comprehensive list of what these might be.  Don’t be alarmed: talk to your doctor and health care team to find out how your treatment might affect you and what you can do to manage any side-effects.
  • Possible side-effects include:
    • Hot flashes
    • Decreased libido and erectile dysfunction (not being able to have an erection)
    • Loss of energy, general weakness
    • Breast enlargement and tenderness
    • Irritability
    • Emotional disturbance including depression
    • Headache
    • Itching, dry skin, rash
    • Gastrointestinal issues: diarrhea, nausea, vomiting
    • Loss of muscle mass
    • Weight gain (mainly due to increased body fat)
    • Shrinkage of testicles
    • ‘Metabolic syndrome’ (increased risk of diabetes, heart disease, and cholesterol)
  • Long-term use (over a year) may lead to:
    • Osteoporosis
    • Lower blood counts or anemia
This list may appear daunting.  However, remember that there are a number of things that you and your doctor can do to reduce the side effects of ADT.
The following approaches can be used to address side effects:
  • You may be prescribed drugs to slow or reverse the loss of bone mass and you should discuss with your doctor whether or not you should have a bone density study
  • Exercise can help to reduce some of the side effects, including bone loss, muscle loss, weight gain, fatigue and insulin resistance
  • Loss of libido can be more challenging to address, but please take a look at our webinar “What’s love got to do with it? Sexuality and the Man with Prostate Cancer” by Dr. Anne Katz.

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