• The Prostate and Testosterone: Lecture by Dr Joseph LaBoissiere

    Dr. LaBoissiere: Thank you. I have kind of a booming voice so if it gets too loud, let me know and I will adjust the mic. Itís certainly a pleasure to be here. I am fairly new in terms of being a physician. I am a fellow and thatís always confusing. When I walk in the room, I introduce myself as the fellow and they go, ďI know youíre a fellow.Ē Iím like, ďNo, Iím not referring to my sex, Iím actually a fellow.Ē What that means is that Iím a urologist. I finished my training. I did four years of undergrad at University of Alberta, four years of med school. I made seven years of residency.
    Then instead of going directly into practice, I made the decision that I wanted to get more advanced training. I am a subspecialist or thatís what Iím finishing up my training in. The way I word it is Iím a functional urologist. Itís a non-official term, but what that means is I donít treat cancer per se. I certainly deal with patients who have cancer. I certainly know the approaches, but Iím not an oncologist. Thatís not my subspecialty. What I do is I try to restore normal function of the urologic system.

    Incontinence is one of my specialties, erectile dysfunction. Iím trying to get you back to normal or as close to normal as you can. Really, Iím a reconstructive urologist. Thatís what it comes down to, thatís what Iím training in. Iíve had the pleasure to train with some of the worldís experts at Sunnybrook and just finishing off with Dr. Herschorn and Dr. Kodama there so itís been a privilege.

    Tonightís talk, I wasnít quite sure what they wanted me to focus on. This is the standard physician slide right at the beginning that says that Iím not being paid to be here. I donít have any stock in companies, et cetera. This second part here, I put on, itís important especially if I was talking in the States, but what it means is that Iím going to provide you with information. Certainly itís going to be accurate, but your treatment is an individualized approach so what I donít want is you to go from here and say, ďOkay. This is what I need to do now.Ē All of it should be discussed in context with your physician who understands the intimate details of your treatment, your diagnosis, et cetera. This is to provide information but at the end of the day, itís information to take back to your physician and to discuss.

    Now, getting to the talk, I do really appreciate the opportunity to come out and it is truly a privilege to be able to take care of others. I love what I do and I love this opportunity because I think the most important job as a physician is to provide information. Gone are the days where the doctor walked in the room and said, ďYou need surgery. Sign the form. Iíll see you later.Ē Thatís not the way it works now. Our job now is to provide you with information so that you can make informed decisions regarding your own health.

    Thatís why I really enjoy these talks because I look forward to the opportunity to provide information. I know thereís tons out there on the internet. Some accurate, some inaccurate. I take advantage of these opportunities when presented to hopefully increase your knowledge just a little bit around your own disease, but maybe things you havenít thought about as well.

    Menís health screenings. This is a cartoon and it paints a bleak picture. You see the physician and the nurse standing here and obviously they havenít had a patient in some time. This is relating, and I know the women in the room will be able to attest to this, but men donít talk about their problems and that's an issue. When we talk about erectile dysfunction, weíre talking about 50% of men over the age of 40 having issues. Itís a huge number.

    Most people donít know that number because we donít talk about it. Incontinence whether itís in the relationship to prostate cancer treatment or incontinence for other reasons, men donít talk about it. Itís a big problem. I see it all the time because I specialize in it, but men just donít talk. We really need to start focusing on menís health and as a urologist Ö And Iím going to go through some definitions just to clarify. As a urologist, I specialize in the genital-urinary systems so thatís looking at the reproductive and the urinary system. I treat men and women, and thatís a common misconception. Everyone thinks that a urologist only treats males. In fact, about 50% of my patient population is female.

    An andrologist, and Iím going to tie this at the end, is somebody who focuses more on menís health and that can be global. Itís not just the urologist. Endocrinologists do it, family doctors do menís health. Andrology is just the study of menís health. What I like to really harp on tonight and hopefully get the point across is that prostate cancer ties in to overall menís health and a lot of the issues that come out of treatment for prostate cancer, so complications of radiation or surgery, incontinence, erectile dysfunction, the effects of being on androgen deprivation therapy or hormone therapy, all of these can tie in to overall male health as well.

    A lot of these issues can occur outside of prostate cancer treatment. This gives me an opportunity not only to talk about prostate cancer which I know all these talks really focus on, but globally talk to you a man, about menís health because the reality is that the majority of men in this room even with prostate cancer are going to run into issues with their health not related to the prostate cancer. Number one cause of death in men is cardiovascular disease.

    Iím going to take this as an opportunity to broach the subject of overall menís health in the context of prostate cancer. Of course, weíre going to discuss the role. Now, when I was being asked to do this talk, I had questioned back to the organizers and said what do they want me to focus on? In my clinic Ö Is that better? In my clinic, I treat erectile dysfunction and low testosterone. I said, ďDo you want me to talk about that?Ē

    Then they sent me back a whole barrage of questions and they said, ďWell, most people get up here and they just focus on prostate cancer.Ē Weíve had lots of talks about treatment options. Weíve had lots of talks about counseling groups after for patients and their families, and treatment of erectile dysfunction, and incontinence. What does the prostate do?Ē I step back and said, ďYeah. I think a lot of people donít know what does the prostate do? Do they truly understand menís health?Ē

    Again, it comes down to that education. If you have prostate cancer, youíve been treated for it, a lot of you in the room or some of you in the room may not even have your prostate anymore, but understanding what the prostate does and how this treatment or this diagnosis has affected you, I think, is important. Iím going to go through normal anatomy and physiology or what the prostate actually does and youíre going to be disappointed.

    Then Iím going to go through the impact of prostate disease. Not just prostate cancer, but prostate disease on overall health because this provides some context to raise some important points. Of course, weíre going to focus on prostate cancer. What I wanted to do though is take an opportunity to talk to you about testosterone. Again, itís not going to be the main focus of the talk, but again itís an opportunity because even though you have prostate cancer and some of you in the room donít, but even if you do, you can still be affected by other issues that affect menís health, low testosterone.

    Some of you after prostate cancer treatment maybe had normal erections and then you lost them five years down the road. That can be due to a variety of reasons. Itís not always related to your treatment. I wanted to take the opportunity to discuss what is testosterone and how does this factor into menís health? It ties in with prostate cancer treatment. It also tries in and hopefully getting you to a healthier well-being.

    Iím going to talk about ways to improve overall health in the context of prostate cancer. One of the questions that I got sent back was is there a way to prevent prostate cancer? Is there a way to improve the treatment or the course if I have prostate cancer? Then how can I improve my overall well-being after prostate cancer is treated. Iím going to touch on that. Then after blabbering on for about 40 minutes or so, hopefully at the end, you understand what an andrologist is. Iím going to touch on what the clinic offers at Sunnybrook. Again, I donít have any stock in there. They didnít send me here to try to drum up business. Iím just here for education, but what we actually offer, and thereís a lot of clinics that do what we do.

    What does the prostate do? If you were to talk to the average male or female and say, ďWhat does the prostate do? What do they tell you?Ē They tell you the problems that happen with the prostate gland where you get prostate cancer, or I hear men can get prostatitis and that sounds really painful and they run in the bathroom every 20 minutes, or their BPH or that enlarged prostate, and I know somebody who canít pee.

    If you actually say, ďOkay, but what does the prostate gland do?Ē A lot of people donít know where it is, what it is, where it is. This is important because when we talk about treatment, youíll understand after I tell you what it does and where it is, why treatment can affect so many different things in terms of normal function. Of course we worry about prostate cancer. A little bit of anatomy, med school 101. Surgeons keep it simple. This isnít going to be a talk using all the Latin terms and everything, this is just a straightforward talk.

    Looking at the man, standing at the side, cut him in half. Rectum is back here, intestines, bladder is here. This is obviously the penis. You pee out of this tube going to the bladder, testicles sit here. This little guy right here, thatís your prostate gland. Why is this important? Look where this is sitting. Iím going to tell you what it does. As I said youíre going to be a little disappointed when I tell you what it does. Look where it sits. It sits right in an important area. Youíve got bladder sitting here, youíve got the rectum back here. This is the external sphincter here. This is what controls continence or allows you to hold the urine in.

    You can imagine then the challenge as a surgeon going in to remove this. How do we avoid damaging nerves, blood vessels, bladder, rectum, all this in the area? Unfortunately thereís excellent surgeons out there. Weíve got the robot now and more advanced techniques that weíre able to do this surgery better and better and better. The robots still establishing itself, robot versus open. Weíre able to do this better but you can understand just by a location how difficult it is and why you can run into trouble because taking this out, we damage this or we damage the nerves here and you get incontinence.

    You radiate this area, you can damage the bladder, you can damage the rectum, the urethra here where you pee out of can fill up with scar tissue so you get the strictures. It is an important area. The prostate, if you just look at it, youíd say, "That just looks like a blob of tissue," but itís actually broken into four different zones and the transition zone is the zone that is intimately associated with the tube you pee out of. This is where you get enlargement of the prostate, benign disease.

    Then we add in the central zone, it doesnít do a whole lot in terms of disease but you can get cancer in any of these locations. The main area for cancer is actually more peripheral. One advantage of that in a sense is that when we go to biopsy, we can stay lateral or away from this drainage tube. 70% of cancers occur here. Then finally, you get this little fibromuscular, just strong connective tissue layer. This right here, these are your seminal vesicles. Theyíre intimately associated. Men sometimes ask, ďWell, why do you go remove that?Ē Thatís part of the process. It all ties in. You can see they drain directly in where the prostate sits so you have to remove these. This is why [inaudible 00:12:53] fertility, et cetera gets compromised with prostate cancer treatment.

    What does it do? I wanted so bad to tell you some profound information that this is a super important gland and thatís why itís causing so much trouble when you take it out and thereís a risk of complications. An actual fact, itís just an accessory organ. What itís involved in is fertility, essentially. Thatís as far as we know right now. What it does is it contributes about a sixth of the volume of the ejaculate. It secretes a bunch of different things. Some buffers, citrate, zinc, prostate proteins like PSA, and weíll talk a little bit about PSA because I know thatís a big thing for prostate cancer and a bunch of other proteins. What it does is it contributes to the ejaculate which contributes to fertility and thatís about it. It doesnít regulate any other hormones, if you lose it, itís not like other parts of the body are affected because of the loss of function and thatís a little bit of a letdown because it does cause a lot of issues.

    Prostate specific antigen, you hear about it a lot. A misconception with PSA is that cancer produces PSA. Thatís actually wrong. PSA is normal. PSA is normally produced by the prostate gland. The reason why it goes up or can go up with prostate cancer is the cancer starts to invade those tissues and disrupt the architecture. It leaks out that PSA and it elevates. Itís not cancer actually making PSA. That gets a little bit complicated when you start to think about you remove the prostate and PSA comes back and thatís because you made some of those prostate cancer cells may have gone somewhere else and theyíre still making it.

    Itís a protease so that means itís an enzyme that affects proteins. It breaks down proteins. What does it do? We donít really know. Again, thatís a letdown. Itís a big thing with prostate cancer but we donít know what it does. One rule we think it does is that it liquefies the ejaculates. When it comes out, it makes it more fluid so it can get where it needs to go. Does this have an impact in fertility? Again we donít know.

    We donít know, but again what we do know is that PSA, at least right now is the best test we have for screening for prostate cancer or case detection. What I mean by that is screening is just taking the average man off the street and doing a blood test and seeing if itís elevated. Case detection is somebody coming in with symptoms saying that, ďSomething is not right. Iím not peeing well. Iíve got pain, et cetera.Ē Now we have a suspicion and weíre trying to detect if something is there so thatís the difference.

    I put this up here. This isnít actually my kid. Itís just somebody I found on the internet. This is usually the expression I get back when I tell somebody what a prostate does and they say, ďThatís it?Ē The problem is, is this. The prostate causes a lot of issues in men so if it doesnít do a whole lot, then what does it do? What causes problems? It causes prostatitis and if anyone in the room has ever had it, it feels like youíre peeing fire, it can. You can get pain. That be related to infection or just inflammation of the prostate.

    This is a benign enlargement. Most benign tumor in men. This is where the prostate enlarges obstructs the passage way and you canít pee. Then of course we have prostate cancer. It causes a lot of trouble. Again, going back to this, the reason it causes trouble is not because itís a change in function, itís because of its anatomical location in the body. Itís associated with the urinary system so bacteria can make its way into the prostate, you can get prostatitis or it can be irritated by prosthesis that causes inflammation or this can enlarge and obstruct the tube and you canít pee or you can get prostate cancer and you can treat that prostate cancer and because of its location, you can run into trouble with incontinence, with erectile dysfunction, with radiation cystitis or inflammation due to radiation damage here and here.

    This is just showing you what the BPH looks like or the enlarged prostate. You can see, it just obstructs this area. The impact of health, this is a distinction for prostate cancer versus other cancer is that unlike colon, unlike lung, pancreatic or liver where youíre removing an organ that plays an important role in the body in terms of function, the impact on health typically with prostate cancer is not related to the loss of the function of the gland but itís related to where it is.

    Itís the anatomy or itís the side effect of the medications. Weíre going to talk a little bit about that. For the men in the room whoís been on hormone therapy, the so-called androgen deprivation therapy, you understand the side effects of those medications. Youíre not running into trouble because youíve lost a prostate, itís the treatment itself. We canít avoid that unfortunately. When we talk about alterations of normal anatomy, these are the things that some in the room may have experienced.

    Erectile dysfunction very common, unfortunately after surgery or radiation. Urethral stricture disease. Fortunately less common but it does happen. You can get where they join the bladder back to the drainage tube, the urethra. You can get that area narrowing down or you can get it further up into the drainage tube and then you canít pee very well. You can get that leakage, the incontinence. Also very common. Fortunately, and Iím speaking as surgeon who specializes in continence, most men wonít need treatment for this.

    By about a year or so, most men will have recovered incontinence to the point where theyíre happy, they donít want to have a surgery. Some will be dry, others will just be content. Only about 5 to 8% of men ultimately will go on to have surgery but thatís 5 to 8% of all men treated with surgery or radiation for prostate cancer. Itís not low. The obvious one is infertility. As soon as you remove these organs, your fertility fortunately itís usually an age where it isnít an issue but this can be a problem especially for younger men and we do diagnose. The youngest men Iíve seen with prostate cancer is 32. Obviously, some genetic component.

    Then radiation damage to the bladder and the bowel. This is just again harping on the anatomy there. I want to take you in a little bit deeper to understand why the anatomy is a problem and why itís a challenge. Memorize this picture in your mind where weíre at. Now, Iím going to show you why incontinence and erectile dysfunction is so common. Now, granted a harder way to look at it but the bladder sitting here, weíre basically looking down into the pelvis, if I was to stand here and put a camera down this way. Weíre looking down. The rectum is sitting back here, prostate is sitting here. Penis is going to be out this way and this is your bladder.

    This yellow part right here so you can see the rectum coming down and intestine here, you can see this yellow. This is all the nerves feeding down. This is the nerves of the pelvis. You could see how intimately associated these nerves are with all the structures. These nerves are the nerves that eventually travel to the penis and cause erections. These nerves are the nerves that travel to the pelvic floor and help with continence. Weíve got to somehow get in here, remove this and if we can preserve this and we canít always.

    The problem is from a cancer perspective, the number one goal is to get the cancer out. Its life over limb so to speak. If we have to sacrifice incontinence or if we have to sacrifice erectile dysfunction as a surgeon, as a physician, thatís what Iím going to recommend. I donít want to go in and do a surgery that is not going to cure you of your cancer. We want to get you to a cure and we do our best to preserve but we donít compromise cancer care and thatís where my job comes in after because once they get you through the cancer, then weíre looking at letís get you back to your life again.

    Iím going to go a little bit deeper. Now, weíre looking from behind. Hereís the rectum here, hereís your prostate. Now, weíre looking as if youíre laying down and we cut you in half. This is called the neurovascular bundle. This is the nerves and the blood vessels. Look how close they sit to the prostate? You can imagine trying to get a margin of tissue to make sure we get all the cancer and trying to preserve this. If we go even deeper, rectum, prostate, hereís where the nerves sit right here.

    Again, this is understanding hopefully for you to understand why itís difficult, why this is common. Itís not easy to avoid this with perfect surgery where we try to preserve this layer here even with perfect surgery, we still have a high incidences of erectile dysfunction and incontinence. Thatís because youíve got small nerves. We canít even see them running in this area. Very, very difficult to preserve.

    This is what makes it challenging. This is why you run into trouble. This is the challenge and the duty we have as surgeons that do research going forward to try to always advance how weíre treating these diseases. Weíre the one job thatís working towards getting rid of our career, our specialty if you think about it. Weíre striving towards the day that weíre not needed and thatís what we do with research. Weíre trying to improve health that way.

    Iím going to shift gears a little bit. Weíre going to talk about how the medications and the treatment can affect you not with the anatomy but with changes to the endocrine system now or the hormone system. This is going to lead into the overall menís health. When I talk about hypogonadism, Iím talking basically about low testosterone and Iím going to talk about why testotesrone is important in your body and I see lots of men in my clinic, in the andrology clinic whether itís been treatment for prostate cancer or as weíre going to talk about men, women have their menopause and so do we and weíre going to talk about how testosterone decreases with time.

    The hypogonadism or low testosterone can be related to a primary cause. We talk about primary, weíre talking about the testicles which make 90% of your testosterone arenít making it anymore. In men as we age, this phenomenon now, this late onset hypogonadism, this is the term as of today, it changes probably every week but you may know it as male menopause or andropause or androgen defiance in the aging male are all interchangeable terms.

    Itís known phenomenon now that as we age, testosterone can get lower and Iím going to talk about the types of things that happen when your testosterone is low. Thereís many other causes though as well. Thereís a reason why youíve actually get mumps, for instance. Young kids getting mumps, you can get permanent testicular damage. They donít have to testosterone. That can feed into fertility and other issues.

    Secondary is when we talk about the signals from the brain coming down and the brain has to signal the testicles to make the testosterone. Is there an issue and this maybe the biggest term of the night but the hypothalamic-pituitary-gonadal axis. Doctors use big terms not because it try to make them sound smart, it just makes it more black and white versus saying, I think itís somewhere here. We give it very specific terms. This is just your hypothalamus part of the brain, pituitary part of the brain and the gonad. When you break it down, smoke and mirrors. Weíre not so smart. Weíre just using big words.

    The impact. Iím not going to ask people in the room but I know thereís men in the room who are on hormone therapy. You may be able to relate to this. What happens when we take testosterone away? You can get bone issues, osteoporosis. You can get hot flashes, not just women, men can get it, erectile dysfunction. That can be related to hormone therapy or the actual surgery or radiation. Cognitive decline. Some of you might feel a little foggy in the brain. You might be getting more forgetful. Not necessarily age. Itís not necessarily other causes.

    Sometimes if the testosterone is low, youíre on androgen deprivation therapy. It can affect the mind. Think about what the body builders are trying to do, pump up the muscles. It doesnít work by the way. It doesnít work well. If you want breasts, you can do that. Iíll talk about that in a second. It is important for the male physique, for lack of a better term. The muscle mass, keeping the pounds off, the obesity. When you take testosterone off, there is documented loss of muscle and an increase in fat.

    Attachment 3615

    It does feed into diabetes, low testosterone. This is going to factor into overall menís health. Metabolic syndrome. Metabolic syndrome referring to diabetes, elevated cholesterol, triglycerides, abdominal, waist circumference, obesity, gynecomastia. Fancy term for men grow breast. It can happen on hormone therapy. This is a big one, cardiovascular morbidity/mortality. We didnít know this before and we know this has been very strongly established that low testosterone can increase your risk of cardiac morbidity so heart attacks and death related to cardiovascular disease. Probably due to direct effects but also a combination off this. Anemia, low blood counts so a lot of effects.

    You can hear me okay in the back? I want to show you this access. This is the brain sitting up here. Hypothalamus, part of the brain, pituitary part of the brain. The brain sends signals down telling the pituitary to send signals, FSH and LH down to the tentacles. FSH says make more sperm. LH says make more testosterone. Then of course the body being brilliantly designed or evolved depending on your beliefs comes back and says, ďStop making it. We have enough.Ē Then when it runs low, the feedback goes away and starts making it again. Very simple system, on/off switch.

    Secondary hypogonadism is a problem up here. This is where the shots come in if youíre getting hormone therapy. Whatís happening is depending on the type of shot, theyíre either giving you a shot that stimulates this which is counterintuitive, if you stimulate that, why does it cause low testosterone? The reason why is the body needs to secrete these in pulsatile fashion. It doesnít secrete all the time. It comes and goes, comes and goes. When you over stimulate, it burns out. Thatís why for some shots, you need to go on the other medication that blocks the receptors, the Casodex if anyone has ever been on that or Bicalutamide because initially the shot will actually increase testosterone levels before it decreases it.

    Thereís another form of a shot that directly inhibits there and then you donít get the so-called testosterone flare. When we do hormone therapy, weíre essentially inducing a secondary hypogonadism or low testosterone state. Primary of course relates to a problem here. The testicles just arenít making it. One of the issues that I saw more and more coming out to Toronto here and just because the clinic that I was working focuses more on low testosterone is that men that are on hormone therapy, when the hormone therapy stops, generally this recovers, but not always and thatís what Iím seeing more of that sometimes with the hormone therapy, for whatever reason this doesnít completely recover and you can have persistently low testosterone after treatment.

    Iím older than I look so I know these movies. Testosterone has many great effects on the body. Thatís obviously the good. It plays a role in some benign disease so some bad disease and then of course it does play a role in prostate cancer as well. Just touching on that. The good, numerous. If you didnít have testosterone when you were developing in your motherís womb, you would be born looking like a female.

    Your sexual organs wouldnít develop and in fact, itís a little bit more complicated, youíd have some abnormal anatomy likely coming out. You need it. This is part of the process that makes you male. I mean, I remember back to junior, et cetera. We talked about when does the voice start to drop, when do you start to get hair on the chest, et cetera? Thatís related to testosterone surges again. You need it for the development of the sperm development and development of secondary sexual characteristics. It gives them the low voice, the beards et cetera.

    Now, what happens when youíre an adult? This is now starting to focus now on overall menís health. Testosterone has a lot of effects in the body as I alluded to if you take it away. Sex drive, libido is largely dependent on testosterone. Overall general well-being, vitality. Just feeling good about yourself, not being depressed can be related to testosterone. Aids cognition in memory. It does factor into the brain. If you want to grow a beard, you need testosterone. Endurance, energy, muscle mass, trying to get rid of the extra pounds there. Fertility, red blood cells, carrying oxygen to all the parts of the body. Bone density here.

    Then whatís not shown here though is that cardiovascular health, very important. A lot of important roles in the body. Of course, it can feed into bad situations though. We talk about an enlarge prostate now. Testosterone, and this is the talk that I go through in my clinic, I say, testosterone actually isnít that powerful in the body. Testosterone actually has to be converted generally especially in the prostate into a more potent form of testosterone called DHT.

    Itís done by an enzyme and in that DHT, affects the prostate. Now, when we have a normal prostate, we know that the prostate cells are growing and dying in a balance and thereís numerous things that factor in there. Androgens, testosterone, DHT, being one of them but thereís numerous other signaling mechanisms and in fact these ones maybe more important when it comes to enlargement than the actual testosterone but when you do get an enlarged prostate, itís because thereís an imbalance now. Too much growth and not enough cell death.

    We take advantage of this. Iím bringing up these two medications because Iím going back to these when I talk about ways of preventing prostate cancer potentially or preventing progression of prostate cancer. Weíre going to talk about a few studies. I know those are boring but Iím just going to highlight the points. We take advantage of this mechanism and say, ďIf we block this enzyme, then maybe the prostate wonít grow,Ē and in fact, it doesnít. It stops it from growing and it actually can shrink up to 25%.

    It can decrease your risk of acquiring surgery if you have a prostate, enlarged prostate by up to 50%. What do you think the side effect of these medications are? A lot of sexual dysfunction. Loss of libido, erectile dysfunction and again all those other testosterone things we talked about. Then of course the androgens testosterone are implicated in prostate cancer. We know that because we treat with hormone therapy occasionally. This could be a talk that could last months if we talk about testosterone, prostate cancer, mechanisms of prostate cancer. I just wanted to raise a few points. Some of them which you probably already know.

    Androgens influence the development, the maturation of the prostate gland. We know that. Exposure of the prostate to testosterone or androgens at key times. We donít really know when those key times are. It plays a role in the development of prostate cancer. It definitely does. Itís not the only one. Cancer is multi-factorial but it does play a role, we know that and weíre learning more about it. They also play a role in the maintenance of established prostate cancers.

    We know that they do play some role in prostate cancer staying there and perhaps even progressing. The other thing I wanted to point though is that testosterone replacement, if you come see me in the office, no history of prostate cancer and your testosterone is low, just say from aging and we talked about putting you on testosterone replacement. It doesnít appear to increase your risk of prostate cancer. We can get the testosterone to the normal level. Now that seems a little counterintuitive. If I say prostate cancer can cause it and maintain it, then maybe having a low testosterone prevents it. Again, that speaks to the complexity of the issue. Itís not necessarily testosterone all the time, itís testosterone at key points and whether it surges, whether it changes, whether the receptors for the testosterone change in some dramatic way. These are things that are being explored but still being researched.

    The reason I bring this up, testosterone as I talk about if we can inhibit this enzyme, maybe we can prevent prostate cancer then. Should we be putting all men on these medications? This leads me into talking about chemo prevention. This is the description of using natural, green teas, blueberries, antioxidants, whatever you pick, synthetic, biological agents to reverse, suppress or event prevent the development of prostate cancer. Weíre starting to learn more about this.

    Does inhibiting these enzyme with this medication, medication that is approved for benign prostate disease, can that prevent prostate cancer? We have extremely good trials done and what I mean by that is they were large, randomized controlled. What that means is, is we had 18,000 men that came in and they said, ďWeíre going to put you in one group or the other. Youíre not going to know. Weíre not going to know. Youíre not going to know whether youíre getting placebo or the actual drug.Ē Thatís the most accurate way to determine whether thereís a cause-effect or difference because it gets rid of confounding variables that way.

    The bottom line from this trial is that, ďYeah. It did reduce the risk of prostate cancer.Ē 30% relative risk reduction. Relative means that it was about 24% of men in the placebo group overtime were found to have prostate cancer and around 18, 17% had prostate cancer in the treatment group. That translates into a 7% overall reduction. Hereís the kicker. There is about 14% increase in the risk of high grade cancer in the treatment group. We donít know. It doesnít make sense.

    We canít think of a physiologic or a mechanistic reason why Finasteride, this drug would increase your risk of high grade cancers. An actual fact, thereís been a lot of debate. A lot of this most urologist donít believe this. Thereís been a lot of explanations for it however the FDA that approves medications has Ö And Iíll show you their statement, because of these findings has basically said, ďWeíre not going to approve this for prevention.Ē The other reason why is there was no difference in survival.

    When we looked long-term, maybe there wasnít as many prostate cancers but it didnít really affect the long-term outcome. We put all men on a medication thatís going to take away their sex drive, their libido, maybe increase their cardiovascular risk, et cetera to decrease the risk but maybe not affect survival and maybe increase the risk of high grade disease.

    Continue with Part 2 below.

    This article was originally published in forum thread: The Prostate and Testosterone: Lecture by Dr Joseph LaBoissiere
    Comments 1 Comment
    1. Nelson Vergel's Avatar
      Nelson Vergel -
      Part 2:

      There was another study, another big one looking at the different drug, Dutasteride, same sort of mechanism. 8,000 men again randomized, bottom lined, showed almost the same number. 23% relative risk reduction but again in years 3 and 4 of the trial, they did see a higher incidence of high grade disease. What does that lead us to? It basically leads us to this statement that for every 150, 200 men, this is the FDA looking at all the research, out of 150, 200 men, thinking of that number, treated with that medication, one man will be diagnosed with a high grade disease just to prevent three to four low risk cancers.

      Now, we know that the natural course of low risk disease is quite favorable. We know that with high grade disease, it’s more difficult to achieve cure. There’s a high risk of developing problems related to spread of the disease et cetera. Lower survivor rates, with higher grade disease. In my practice, I actually spoke to some of the … Dr. Klotz who’s at Sunnybrook, who’s one of the world’s experts in prostate cancer treatment. The bottom line is we’re not using this simply for prostate cancer prevention.

      That being said, we do use it for men with enlarged prostates. For men that have indications for benign disease, we certainly will use this medication. In that scenario, the benefit outweighs the risk but with this, with all this information, it’s probably safer not to be using it. Now, I go through a few others but I didn’t put a slide up there but I want to touch on one other study. I don’t want to give you all the details, I’ll give you the bottom line is that because I’m speaking to an audience, I know where men already have prostate cancer.

      If you’re on act of surveillance and there’s some men in the room and so what we mean by that for those that don’t understand is for most low risk cancers now, we’re advocating that you go on after surveillance which means that we’re recognizing that most of these low grade cancers are going to be a fairly benign course. That means that it’s probably not going to become a problem for you in your lifetime.

      We just watch you to make sure that your disease isn’t progressing and that we don't have institute treatment. If we do, we do it at a time where it’s absolutely needed. Then hopefully we prevent over-treatment which has been one of the big things that’s come up with screening and all of the complications, erectile dysfunction, incontinence, et cetera. Then they ask the question if it doesn’t prevent or if we can use it to prevent prostate cancer, can we use it in men on after surveillance to prevent progression of the disease?

      That was called the redeem trial. The way I think about it is trying to redeem this drug in the use for prostate cancer. That was actually done in Toronto. The bottom line is it doesn’t appear to prevent progression. Again, talking to some of my colleagues that are experts in this field, we don’t generally recommend this. We don’t put it forward as an option. That’s just speaking to the group that has prostate cancer obviously.

      Now, we talked about chemo prevention, selenium and vitamin E and I’m going to talk about this in the context of do we prevent prostate cancer? A lot of these things also come up for men with prostate cancer. They ask about all these nutrients and things like that can be helpful. Selenium and vitamin E very large study, you don’t usually see this for herbs or over the counter stuff or these are the macronutrients, et cetera, but this was a very large study, 35,000 men. What they looked at is if you gave a group selenium, vitamin E, combination or placebo was there any difference in the instance of prostate cancer and there wasn’t.

      In fact, there was a trend towards an increase risk on selenium and there definitely was an increase risk with vitamin E. These actually might be harmful to take. I do see the occasional men coming in on them because just Google’ing tonight, reading online, I found a few websites looking at selenium for prostate cancer and vitamin E, et cetera. This is where I take this opportunities to try to bring out the information that we have.

      Vitamin D, there’s no evidence at present. They’re really looking at this. It's being studied but for this talk tonight, up to date information, not enough evidence at present to warrant its use. Soy, same thing. Lycopene same thing. Green tea, does anybody drink green tea? Yeah. I mean I like the taste of it. It’s not harmful. There actually is a very small study, very small study that said it may lower your risk of developing prostate cancer.

      More studies are certainly required, but I don’t have any problems when somebody comes in and says, “I want to drink a few glasses of green tea [inaudible 00:45:12] because so do I.” This is where it gets a little interesting. We talked about overall men’s health. We talked about diabetes. We talked about elevated cholesterol, et cetera. We say, “Well, does these sort of pathways, glucose pathways, cholesterol pathways, inflammation, et cetera, do those affect prostate cancer?”

      They’ve actually looked at Metformin, a drug that’s used to treat diabetes, type 2 diabetes. They wanted to see does this prevent development of prostate cancer or does it have any role in men with prostate cancer? In terms of preventing, there’s no evidence right now at present. There’s ongoing studies actually. Though there is some evidence that it may inhibit the development of castrate resistant prostate cancer as well as death from prostate cancer.

      These are new insights that are coming out. There’s ongoing trials looking at Metformin in the role and it’s exciting to see where they’re going because this is stepping way outside the blogs thinking about a diabetic drug that may have a role. Statins also the same thing. Statin has lower cholesterol levels, et cetera. It may affect late stage carcinogenesis. What I mean by that is it may affect progression of the disease.

      Again, these are drugs that are being studied in the context. This is stuff that may come out in the next few years either yes or no. When we talk about anti-inflammatories, so nonsteroidal anti-inflammatories, ibuprofen, et cetera, there’s conflicting evidence. Some studies show yes and we go, “Great, there’s a study.” Then somebody just published a study that says it doesn't and then back and forth, back and forth. That’s the challenge is trying to get really good studies done to do this and these studies are difficult to do. You can imagine a big study, 35,000 men. Especially if we were using a pharmaceutical drug, money, time et cetera, it’s very, very difficult to do these big studies. It’s quite impressive that groups were able to do this.

      Now, I’m going to start getting into, and this is going to tie it in … Are we doing okay for time by the way? Are we doing okay? There are other things that factor into cancer risk but also your overall health. Again, anytime I see a man coming in with prostate cancer, erectile dysfunction, low testosterone, I take it as an opportunity to sit down and say how are you doing otherwise? How’s your diet? How’s your exercise? Are you smoking? We take these opportunities when we get them because again with men we don’t get them that often. You see the doctors like they see again in 10 years.

      Smoking. Does it cause prostate cancer? We don’t have good evidence for that. Does it cause a lot of other cancers? It does. I was looking back through some of the other talks here so I don’t want to be that physician that’s like, “Quit smoking because everybody says it.” This does affect your body in numerous ways, cardiovascular disease and then multiple different cancers. Cancers that we deal with, kidney cancer, bladder cancer, et cetera. It doesn’t appear to increase your risk of getting prostate cancer but if you have prostate cancer, there is some evidence that it increases the risk of recurrence, biochemical so that’s when your PSA starts to go up.

      Metastasis or spread of the disease and perhaps even mortality are death related. Now, this is important, prostate cancer specific. I’m not talking about death because you had a heart attack or something else or death from another cancer, I’m talking about death-related to prostate cancer itself. Obesity. This is a little bit interesting. If you want to avoid lower risk prostate cancer, pack on the pounds for sure.

      You may be at a high risk of high grade prostate cancer. Again a little bit conflicting. What I say here is I say, number one, lower risk is better than higher risk. The other thing is obesity carrying too much extra weight, et cetera significantly impacts on your overall health. Again, remembering number one cause of death for us is cardiovascular disease. This is huge. They’re talking now about obesity being the number one preventable cause of death in the world surpassing smoking. It’s a big deal.

      Diet. This comes from studies. The biggest study looking at when we got the Asian cohort moving to the western society. Healthier vegetables rice et cetera to Alberta style diets, right? Red meat, high fat. It’s high fat, low vegetable diet. It may impact on prostate cancer risk. This is an extremely difficult thing to study though because it can be multi-factorial in terms of diet. It’s hard to just say, “Yes, diet was the cause because it’s hard to wipe out all the other confounding variables and just focus on diet.”

      Does diet impact? Maybe, but what does diet impact on? This. What does diet impact on? This. Again, even if this doesn’t prevent progression of your disease, development of the disease for men in the room who don’t have prostate cancer that is here tonight, it significantly impacts the rest of your health and as a functional neurologist, all this stuff, “Oh, this is big time for erectile dysfunction,” because erectile dysfunction, cardiac disease is strongly related. I’m going to talk about that a little bit after.

      Metabolic syndrome, diabetes, obesity, elevated blood pressure, this is a constellation of things. Elevated triglycerides, decreased HDL cholesterol. What do we know from a urologic perspective. As a urologist where do I see this impacting on my diseases? It increases your risk of benign enlargement of the prostate. It increases your risk definitely of a erectile dysfunction. In fact, when I see men with erectile dysfunction, again, I take it as an opportunity to screen for diabetes, to screen for high cholesterol, metabolic syndrome, because if they do have any of this, treatment of this may help to improve this.

      Risk of kidney stones. Anybody in the room ever have a kidney stone? You don’t have to put your hand up but if you have. Like I said I treat women and I’ve talked to them that had kids and kidney stones and they say, “Take a kid any day of the week over kidney stones.” These can be particularly nasty. This is the big one though. This is what I really, really, really want to point out. I know I’ve been going all along but in the end, you’re sitting in this room and you got prostate cancer or you’re thinking about prostate cancer and you’re worried about prostate cancer maybe but you’re here.

      I don’t want to push the prostate cancer side. It’s a big deal. I understand that as this physician that deals with that. I also want to encourage you that you’ve also got your health to worry about otherwise and you’ve got other issues and take it as an opportunity to get into the best shape you can and live the healthiest lifestyle you can because even if that does an impact on your prostate cancer, so preventing progression or for those in the room who don’t have prostate cancer, preventing the actual occurrence of prostate cancer, it will significantly affect your overall health.

      That’s not only important for the prostate cancer itself but also dealing with the treatment, recovery from surgery and radiation because your body needs to heal and the healthier the body is, the easier it is to heal. I mean I’m getting older. I recognize I’m saying that to a crowd that’s a little bit older than I am but I’m starting to feel the effects of aging as well playing with my kids. I mean it takes me two days to recover after running around for five minutes.

      The body is healthy as it can be is going to help you with your prostate cancer whether it infects prostate cancer directly or just affects your ability to get on with your life and to heal and to have that vitality again and feeling good about yourself. This is just hammering that point. What happened there? There we go. This is just hammering that. It just affects overall health in various urologic conditions.

      I’ve blabbed enough. You’re still wondering, “Well, what do I actually do?” What is andrology? I alluded to beginning. It’s medicine that just focuses on diseases and conditions specific to men. When we think about andrology though, most men think about it in terms of infertility so the young guys coming to the office and for some reason, they can’t have kids. The hypogonadism so that’s the men coming in the room and they say the couch calls me. That’s the men that can walk past the couch without laying down and having a nap or the sex drive is gone.

      Usually it’s the partners in the room saying there’s an issue or erectile dysfunction. That is where we tend to focus as urologists on andrology but recognizing that diseases for me are also cardiovascular, et cetera and there are family doctors, endocrinologists, internists, that specialize on conditions that affect men. What can I offer as an andrologyst or somebody who deals with complications of conditions specific to men? I can help to manage erectile dysfunction and that’s probably about 70% of what I do in the clinic.

      I can help you with hypogonadism and that’s with low testosterone and issues related to that. If you’ve got low testosterone and you have a history of prostate cancer, it doesn’t mean that you can’t have testosterone. There’s obviously a discussion but a history of prostate cancer does not mean you can never have testosterone replacement again. Obviously it can’t be active and we need to make sure that it’s cured et cetera. Don’t think just because you have prostate cancer and if your testosterone is low, down the road, that it’s game over. It’s not.

      Then of course management of infertility. Now, I don’t focus on this specifically. There are more subspecialize individuals that focus on infertility because this can be multifactorial, very, very complicated. I’m not going to go to the treatment but I’m very happy to answer any questions related more to this. What I want you to understand is that the etiology of low testosterone and erectile dysfunction even if you have prostate cancer can be multi-factorial.

      It doesn’t necessarily mean that it’s related to your treatment. It can be related to aging. You’re not immune to other conditions that can happen in men that haven’t been diagnoses or treated for prostate cancer. Hypothyroidism, obesity can affect testosterone levels, excess estrogens, kidney dysfunction, et cetera. It is multi-factorial and that’s why a specialized clinic is ideal because if I get you sent to my clinic and everyone says they have prostate cancer, that’s what’s causing the issue, I step back and go, “Maybe, but maybe it’s something else or maybe it’s a combination because we don’t want to miss that something else if it’s there because maybe we miss an opportunity to treat something. We don’t have the blinders on.

      I’m just a little bit just a stick out there too because as I alluded to with this, there are men that maybe even men in the room who are struggling with this and in incontinence and there are treatment options available, we can help. You just have to ask. I’m not embarrassed to talk about it. I’m not embarrassed to get up here. I mean my kids know me as the dinky doc and that’s how I’m introduced at parties for them and I’m not ashamed of that because it’s a big problem.

      I understand just like most of the physicians do, the impact that cancer can have on your overall well-being, that treatment for cancer can have on your overall well-being, but also complications of either cancer treatment or just getting older, or trauma, or something else running into these issues. Erectile dysfunction, as I said, not talked about, it’s a big deal. We recognize that in relationships. It can have a significant effect on men’s mental health as well as their physical health. I just want to encourage you that if you’re out there, there‘s individuals who understand and are willing to help and to sit down and talk with you about it. That’s all I have to discuss so thank you for your time.