Testosterone, the male androgen, is mostly (though not exclusively) produced in the male testes when they receive a signal via another hormone called leuteinising hormone (LH), which is generated in the pituitary gland located in the brain.
LH production is controlled by yet another hormone, leuteinising hormone releasing
hormone (LHRH) (which is different than “plain” LH), which is produced in the hypothalamus, a gland located adjacent to the pituitary gland in the brain. This complex interaction of the pituitary, hypothalamus, and the testes regulates the production of testosterone. Whether via drugs or surgery, altering the interactions between these three glands can substantially decrease or even halt the production of testosterone in the testes.
Normal testosterone levels can range from around 250 to 800 nanograms per milliliter (ng/ml). ADT’s goal is to lower your testosterone levels to less than 20 ng/ml. Some doctors feel that a level less than 50 or 30 ng/ml is sufficient, but experience in our support groups suggests that bringing your testosterone level to below 20 ng/ml is a better goal for more effective ADT. (http://www.ncbi.nlm.nih.gov/pubmed/19680526?dopt=AbstractPlus)
There are different methods to obtaining a castrate level of testosterone. They are:
Surgically Controlling the Production of Testosterone
Testosterone production can be permanently reduced via a surgical procedure known as an orchiectomy. This is commonly known as surgical castration. Orchiectomy consists of the removal of the gonads and the spermatic cord through an incision in the abdomen. An orchiectomy is not reversible.
GnRH Agonists- Chemically Controlling the Production of Testosterone
Testosterone production can be controlled chemically by a class of drugs known as gonadatropin-releasing hormone (GnRH) agonists. These drugs are:
- Eligard
- Lupron (The most widely administered GnRH agonist)
- Trelstar
- Viadur
- Zoladex
All these drugs slow down testosterone production by interfering with the LHRH signaling process. They are the most common method of administering ADT in economically advantaged regions.
*CAUTION – Evidence has confirmed that these drugs, as well as surgical castration, increase your risk for developing metabolic syndrome, including diabetes, heart problems, and vascular complications. As of November 2010, the FDA has required a “Black Box” warning on these drugs because they have been linked to increased cardiovascular risk, i.e. myocardial infarctions (heart attacks) and death. If you are already taking, or are considering starting any of these drugs, consider making an appointment with a cardiologist for an initial exam, and make sure that your doctor regularly monitors your blood sugar and possible signs of any heart damage.
Side Effects Caused By Reduced Testosterone (ADT)
Many men mistakenly believe it is the orchiectomy or the LHRH drugs themselves that cause the negative side effects of ADT. This is not true. These negative effects are caused by the loss of testosterone in the body. The degree, incidence, and frequency of these side effects will vary greatly from man to man. Some men report that they “barely” experience any side effects, while others report that the side effects of being deprived of testosterone has a substantial negative impact on their quality of life. There is no way to predict how you might experience any of these side effects, which may include:
- Increased risk of developing cardiovascular complications
- Increased risk of developing metabolic syndrome and diabetes
- Increased risk of developing Colorectal Cancer (Journal of the National Cancer Institute, 2010)
- Hot flashes (sometimes called hot flushes) and night sweats
- Loss of muscle mass
- Loss of libido
- Shortness of breath
- Increase of blood pressure
- Feelings of confusion
- Disorientation
- Weight gain
- Neuropathy
- Breast growth
According to a 2010 report from the American Society of Clinical Oncology “endurance, upper extremity strength and the physical components of the QOL are affected within 3 months of starting GnRH agonists.” Ask your doctor if you should start an exercise program at the beginning of ADT in order to reduce the potential for physical deterioration associated with living without testosterone.
PSA FLARE
When you first start a GnRH agonist, your testes will attempt to compensate for loss of signaling created by the ADT drug and will over-produce testosterone. This testosterone “flood” will do exactly what you don’t want: cause the prostate cancer to grow. This is especially dangerous for men with very advanced disease, but never a good thing for any man with prostate cancer. This situation can result in significant disease progression and increased pain. When the testosterone flood happens, there will be a “PSA flare,” as the PSA increases due to progression of the disease.
Ask your doctor if you should take an anti-androgen medication such as Casodex, at least ten days prior to starting a GnRH agonist.