Testosterone supplementation therapy...understanding the complexity involved.

The cause of prostate cancer has never been determined. In simpler words, no one knows what starts the cancer process in the prostate gland. There are hypothesis. On one side, some say that in aggressive cancer when a diagnosis is made, a number of men have LOWER levels of testosterone. On another side, some point out that men with high testosterone are at increased risk to develop prostate cancer. So, who is right? The answer is no one knows with a high degree of certainty.

What it is known is that in the presence of prostate cancer, androgens (testosterone and its metabolites) drive the growth of cancer cells. How do they know this? They know it by the response that cancer patients demonstrate when treated with androgen deprivation therapies. This response it directly proportional to the state of the patient’s tumor load at the time of the diagnosis. In general the response is poor in widely disseminated disease and better in earlier stages of the disease. As a matter of fact, in extremely disseminated PCa, there is short or no response to androgen deprivation.

Prostate cells are predominantly androgen dependent, but in the prostate gland there is a number of androgen independent cells that we are born with. This is one reason why androgen deprivation as a therapy is never “curative”. Prostate cancer is therefore highly androgen dependent in its initial stages and typically responds well when androgen deprivation is initiated at that stage. In time and through a variable progression rate, cancer cells learn how to survive by using different mechanisms. There is a natural process to insure their survival by which androgen dependent cancer cells become androgen independent.

Prostate cells have in their surface chemical entities that behave as doors to other chemical entities. These are known as androgen receptors (AR) and like a lock and key only accept other chemical entities that “fit”. These receptors are the way that these cells multiply, grow and die.
There tends to be an equilibrium as new cells are born an others die in a process to maintain a balance of the physical conditions of the prostate gland.

In normal conditions, these androgen receptors(AR) are charged with the way the prostate gland maintains itself. They(the ARs) preferentially link to a very potent metabolite of testosterone known as dihydrotestosterone (DHT). When these two chemical entities link (the AR and DHT) they form a complex that then is able to move to the cell’s nucleus and start a process known as cell cycle or cell division (by which the cell splits into two “daughter” cells). This is a normal process (homeostasis) triggered to maintain a balance within (in this case) the prostate gland.

In the carcinogenic process of the prostate, the normal proliferation rate of the cells tends to be slow or close to that of normal cells. This can change as mutations accumulate and the normal character of the cells change. In time and through a process of dedifferentiation cancer cells try to survive by acquiring a very different character. The cancer cells can learn how to survive by using other chemical entities than androgens. It is known that the AR can link to growth factors such as epidermal growth factor (EGF), vascular endothelial growth factor (VEGF) and many others to regulate cell-cycle, cell death and differentiation outcomes. In short, these growth factors are one way for cancer cells to acquire androgen-independence.

This is a complex process. Difficult to define precisely because of number of the different possible pathways and receptors involved. Normal prostate cells and prostate cancer cells also exhibits estrogen receptors. The mostly express is estrogen receptor Beta (ERb)and some do express estrogen receptor Alpha (ERa). These can drive prostate cancer growth in the presence of estradiol (estradiol is derived from testosterone by an aromatization conversion). This is why testosterone replacement therapy (TRT) in patients who have been treated for PCa needs to be instituted with caution to monitor metabolic products and avoid any of them to drive cancer progression.

Many men, otherwise healthy, with low testosterone resort to supplementation with testosterone without understanding that the addition of this external source of testosterone will eventually reduce his normal source of internal testosterone production. This is a “for life commitment”, as with time it will cause testicular atrophy and no endogenous testosterone production.

In men who have been treated for prostate cancer it is important to control the metabolic products of testosterone. It is also of extreme importance to differentiate patients that have no prostate (surgically removed) from those that have been treated with radiation. Given the complexity of possible receptors involved, men need to be treated by physicians that closely monitor the metabolic products of testosterone. Mainly dihydrotestosterone (DHT and estradiol (E2). To add testosterone without monitoring these is risky. PSA by necessity needs to be monitored closely to prevent unrecognized progression.

In summary, TRT might be an important addition to improve QOL in PCa patients. It is important to understand the details and the necessary commitment to undergo this therapy. Physicians that understand the process are a requirement. Finding one might not be easy. As one who did it, proceed with caution.

RalphV

Hello Arnie,
Glad to see you are doing it in the proper way. Glad that you also included the list of tests needed to be on the safe side. I did basically the same as you when on TRT some years ago. I am physically castrated and had no need for the LH test, but had control of the others. I also used Arimidex when the estradiol started to become elevated. A dose three times a week did the job.

Thanks for the added information and wish you the very best in your TRT process.
BTW, for what is worth, my PSA never became detectable during TRT. I had to stop treatment because of an increase in liver enzymes which was resolved after stopping the testosterone injections. I had a T4 diagnosis with GG 4 and in spite of that TRT did not "fuel the flames".

RalphV

Fairwind,
Not sure if you are asking me. I cannot say it did. Ten years after the orchiectomy I decided to try TRT. Maybe I was expecting too much and maybe that is what makes me say that it did not make feel so much better. I probably was too far gone physically to benefit. That said, I think if tried sooner it would have probably resulted in a benefit. Because the T4 diagnosis, I did not have the courage to try it sooner.

RalphV

JohnT,
You must have noticed that I wrote “curative” (in quotation marks). Dr. Leibowitz considers PCa a systemic disease from the get go. For him surgery or radiation for localized disease are a waste because they are not “curative” given that the disease is always systemic. I have in our support group two men who did the 13 months of Proscar, Casodex and Lupron with Dr. Bob and both had PSA recurrence. Like I said, androgen deprivation is in general not considered a “curative” therapy and that includes Dr. Bob.

RalphV

"curative"
Cure can have several meanings depending on the emphasis of the speaker. The broadest definition is when a person dies of some other cause than the original condition. In that case the condition was cured by death from alternate cause. There are other more proximate definitions which include relief from symptoms, no evidence of disease, recurrence at levels below that necessary for further treatment, etc.
No one can say that his cancer, of any type, has been eradicated from the body to the last, final rogue cell. Science is incapable of determination at such a microscopic level. Thus all definitions of "cured" have ambiguity.

mspt98,
First, you seem to be on safe ground for TRT. That said the key is to improve your QOL without increasing the risk of recurrence. As your T increases with the supplemented testosterone shots, your body can metabolize testosterone to estradiol(E2) and dihydrotestosterone(DHT).Excess E2 can promote breast enlargement and drive cancer growth if estrogen receptor-alpha happens to be present (not very probable).

Because of this, it is reasonable to ask your doc if it is possible to avoid the excess breast enlargement by inhibiting E2 with an inhibitor (Arimidex or Femara). To do that test your blood estradiol.

Tell him that you know of someone who experienced breast enlargement while on TRT and they helped him with those meds. He should not be PO by this and go along and help. Keep a close eye on PSA. Wish you the very best results.

RalphV

mspt98........I agree with Ralph, that based on your stats and timeline, you seem to be a good candiate for TRT therapy. Most uros don't get beyond the administering and Rx of testosterone, in any form. It's really outside their realm, and should be an endo's area. But most endos, at least the ones I've seen, don't want to take the time to get into the weeds of male hormone issues. if you have a thyroid or diabetes issue, they're all too willing to tackle it. But present with hypogonadal issues, especially with the PCa survivor factor thrown in, and they run the other way. I went to one local endo, and another U of Penn where I had my surgery. His specialty was male hypogonadism, and both still dismissed me as perhaps having a psychological problem. So if you can find an endo, or even a uro who is willing to listen to you, and include you as a partner in your own rehab, that would be great. I've found that if you do your research and due diligence, and present to a doctor (your uro) that you're not just following junk science, they will listen. ---------in addition to the breast enlargement issues tied to high levels of estradiol, the estrogen dominance that a lot of us experience in middle age presents symptoms such as muddled thinking, inability to lose weight, belly fat despite working out, continued low sex drive, even hot flashes and night sweats. You might google testosterone to estrogen/estradiol ratio. That's the key...back in our 20's and 30's it was in the 40 or 50:1 ratio.......now mine is 20:1 or less. The way we knew I was converting via aromatse enzyme was that no matter what dose or method of "T" supplementaion, the estradiol levels would follow the "T"  like a shadow. Be sure to do the labwork, and see if after administration of "T", your estradiol levels stay static, or whether they move, like mine, with the levels of "T".......good luck as you proceed and keep us posted

Arnie in DE

Hello mspt98,
Hey, I am a LSU graduate (eons ago), but unfortunately do not know any experts in BR. Although you might never need him you have a PCa expert medical oncologist in Oliver Sartor at Tulane in NO. He really knows his stuff!

Again, wish you the best possible outcome.

RalphV