Supplementing serum testosterone to higher levels may positively impact muscle growth but has limited effects on prostate growth and cancer initiation/propagation.

“so so Ted let me make sure I understood that I mean at the high level that made sense but some of those examples and numbers are are kind of mind-boggling to me so you're saying if I heard you correctly that that uh prostate tissue and hair follicles might reach saturation as low as 250 nanograms per deciliter of testosterone which as you point out is very low uh that's that's a level that is probably at about the tenth percentile of the population for men over 18 suggesting that 90% of men walking around even not taking testosterone replacement therapy are already at levels of saturation for hair follicles and for prostate you alluded to the fact that presumably for anabolic needs in the muscle the saturation level would be much higher so the so first of all let me pause before I go on am I getting those numbers about right yeah and the way to think about it is in the prostate and in heroles there's there's five Alpha reductase that as soon as the as soon as testosterone enters a prostate epithelial cell it is immediately converted to DHT which is about 10 times more potent than testosterone so if you really wanted to kind of you know fiddle with the math actually if you didn't have DHT around the saturation level that you would need for the within to for prostate maximal saturation You could argue would be 2500 y nanog per Mill right but the idea is that there's amplification of the effect of T by converting to DHT by about maybe 10x so does that imply that on average if a man is taking exogenous testosterone um so he start let's say he started out at 300 nanograms per deciliter which truthfully would still be considered hypogonadal — and he gets replaced to 800 nanog per deciliter would you not expect him to experience a a BPH trajectory growth or hair loss or any of the things that might be associated with the increase that he's going to experience in both testosterone and DHT yeah I mean most of this most of the data on on T supplementation within the prostate you're going to see more of a precipitation of BPH symptoms again we talked about the differential and so there may be a little bit of a bump in terms of lower urinary tract symptomatology but it's pretty subtle and in fact one of the biggest um genes that uses or is Androgen responsive is PSA and most people when you and you augment their their testosterone that's how they kind of measured or estimated the saturation to be between 200 and 250 Moira did a nice study he's a former uh Drive uh guest they estimated to be around there and and you can actually see that because most people that you supplement from let's say 3 to 800 you're not going to see a big bump in their PSA and so that would be the premise whereas if someone's at three they may have pretty limited you know muscle mass and and and yet you bump them to 800 and you see a real nice impact so let's now talk about bringing it back to prostate cancer a paper that you and I discussed probably on your first uh your your first uh appearance on the on the drive which was that paper that came out in the New England Journal of Medicine back when we were residents God so this is I I really think this was probably 02 or 03 and it was a it was at least for me not being a urologist but but still being someone that kind of at least read the New England Journal of Medicine pretty pretty remarkable in in what it suggested which was the lower a person's testosterone the greater the risk of highgrade uh prostate cancer um so so maybe for folks who don't remember that discussion can can you bring us back up to speed on that on that point and and the findings of that paper which I think are starting to make sense by the way in light of what we're talking about so the main driver that people have always focused on the um the dependent kind of fuel for prostate cancer has always been post postulated to be testosterone and in a normal prostate cell we talk about these different thresholds obviously when uh a um the gland undergoes mutations prostate cancers develop some of the wiring is is is skewed and you can develop a cancer now um the initial uh study basically showed a correlation between grade and aggressiveness of prostate cancer with um with testosterone and and and and PSA value showing a lower PSA was associated with a higher grade prostate tumor and that concept was something that always intrigued me and and I think during the time we did our first podcast which was in 2018 or or so I had been working on this on again study that exact same concept and understanding well if a higher grade prostate cancer is a cancer that is um less similar to a a benign prostatic gland it's more dissimilar it's more um altered what are the factors”

“and probably is again underscores the idea that supplementation of your serum testosterone levels to higher levels will have a end organ effect that's positive perhaps within muscle growth but has pretty limited results in terms of its impact on the prostate growth and initiation and and and propagation of prostate cancers”

“whereas in muscle um levels probably have to be much higher to get the anabolic effects from a steroid in muscle to promote muscle growth and muscle Mass”