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Androgen Ablation

The first step in this procedure is the Total Androgen Ablation Phase. It is not only important for the systemic treatment of the cancer but for enhancement of the local eradication of disease.

The key to understanding how hormonal therapy works is the understanding of how the male hormonal feedback loop functions.

To understand this hormonal chain, let's start at the beginning - the brain, where the hypothalamus makes among other things, a substance called LHRH (luteinizing hormone releasing hormone), which acts as a chemical signal. It's dispatches are in pulses, like Morse code, or flashes of light, to the nearby pituitary gland. It's message is "Make LH and FSH" it tells the pituitary. LH (luteinizing hormone) and FSH (follicle-stimulating hormone) are other chemical signals, and they bring us to the testes, where LH motivates certain cells (called testicular Leydig cells) to make testosterone. The FSH component has a major effect on sperm production.

Testosterone then brings us to the prostate. Testosterone circulates in the blood and enters the prostate by diffusion. Soon it undergoes a metamorphosis, into a hormone called DHT (Dihydrotestosterone) - which is more than twice as powerful as testosterone. DHT is not believed to be as important in prostate cancer as it is in the normal prostate. Both testosterone and DHT can bind to the same receptor in the prostate cell - like two different keys fitting the same lock. When DHT binds itself it does so with great affinity; testosterone does not cling as strongly to the receptor. When DHT and testosterone hook up to the receptor, it attaches itself to DNA, which activates certain genes.

Testosterone in the blood circulates back to square one, the hypothalamus, which acts as a thermostat. It measures the level of testosterone and decides whether to boost or cut back on LHRH production and the cycle begins again.

So - the main components of the feedback loop are (1) the hypothalamus in the brain, (2) the pituitary gland, (3) the testes, (4) the prostate. In addition to these principal players, the adrenal glands sit on top of the kidneys and make weak male hormones called "adrenal androgens" including androstenedione,dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS), plus small amounts of testosterone. These are minor players and make up only 5% or less of the total hormonal stimulation of the prostate.

Since testosterone is the fuel for prostate cancer cells it is obvious that the ability to break this loop at any point will cut off the supply of testosterone and starve the cancer cells to death. There are several target points for attack by hormonal therapy.(1) the hypothalamus to pituitary connection by using estrogen . This cuts the flow of LHRH. Estrogen is the only true hormone of potential use in this therapy if this target point is chosen. It is also possible and preferred to use a chemical called Leuprolide Acetate (Lupron) at this point since it has less adverse side effects. As stated previously the hypothalamus works as a light house by sending out the equivalent of flashes of light which signal the pituitary gland to make LH and FSH which are part of the chain in the production of testosterone. The Lupron basically turns the light on all the time. This tricks the pituitary; because no flashes or pulses are received, it does not make LH and breaks the production chain for testosterone.

(2) The link between the testes and the prostate can be broken by the use of a drug called Ketoconzole for the short term. This breaks the flow of testosterone to the prostate. It is not as effective as other drugs in this therapy so is used only as short term solution when rapid results are needed.

(3) It is possible to block the receptors to the prostate so that none of the LHRH, LH, FSH, or testosterone (androgens) will bond to the receptors. This is done by using a drug called Casodex which is the compound "Bicalutamide". As stated previously the androgens (LHRH, LH, FSH, and Testosterone) fit into the prostate receptors like a key in a lock. The Casodex works by fitting into the same locks as a substitute key. These effectively keeps out the undesired androgens.

(4) In prostate cells testosterone is converted by an enzyme into the more potent DHT. This enzyme can be blocked by the use of a compound called 5-alpha Reductase inhibitors. (Proscar).

It is important to realize that hormone treatment by itself will NOT cure prostate cancer. It will buy time if used alone. The reason for this is that there are hormone sensitive cancer cells and hormone insensitive cells. The hormone treatment will kill (starve) the hormone sensitive cells but NOT the hormone insensitive cells so the cancer will grow. A recognized medical authority on prostate cancer from Johns Hopkins stated "To try to kill prostate cancer with hormone therapy alone is like trying to kill cockroaches with hair spray!!" .

Now, understanding some of the biochemistry in the biofeedback loop and the function of some of the chemicals involved, it is easy to understand the treatment protocol being prescribed by the Cancer Center for treatment of my cancer (PSA 10.4, Gleason Number 7, TNM System Classification T2b.




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