foreign I'm talking about testosterone as a ubiquitous molecule that's undervalued and under appreciated my disclosures are I've been part of the AUA guidelines as a non-urologist helping develop the guidelines for ED testosterone deficiency Peyronie's and now for prostate cancer screening and I work I do some work for a few small testosterone companies one of the people that are most influential in my life was Andy gay and this is a photo of Dr Gay and Abe morgenthaler and mo Kira and abzul Trace back in 2015. and it's important to remember all the the people that really have an impact in your life so we're going to speak about why testosterone therapy is so underappreciated um it's important for male sexual desire muscle mass mood motivation but why is then testosterone deficiency and testosterone therapy undervalued is it because in a prior life it was the domain of bodybuilders at Super physiological levels and we know that Mark Maguire and Barry Bonds everyone's still waiting to get into the Hall of Fame if they ever do we know that the man who's hit more home runs than anyone has never Alex Rodriguez still hasn't been elected to the Hall of Fame so it's because of anabolic steroid use and is testosterone that anabolic steroid testosterone deficiency is associated with vital General medical conditions facing all societies type 2 diabetes obesity osteoporosis and coronary artery disease what I do day in and day out to see men for two issues erectile dysfunction and because I do testosterone levels on those men and because I'm evaluating the cardio metabolic risk of those men I under undercut I uncover a lot of testosterone deficiency and what happens or what's happened is it's no longer being done in primary care they're not repeating testosterone and they're not repleting testosterone because they're fearful after the FDA changes the labeling in 2015 to prevent the desire to prescribe testosterone for comorbid testosterone deficiency meaning testosterone deficiency that's associated with obesity and high blood pressure and dyslipidemia so testosterone therapy has shown compelling health benefits and most recently testosterone levels have been associated with most urgent medical issue that we've been facing in the last few years and that's covet 19. um it's been shown to reduce the rate of severe infection and it's been shown to be associated with the highest rates of mortality which is really interesting because the last thing that you're going to think about when a patient's in the ICU is checking a testosterone level for their covid and supporting them with testosterone therapy so the T trials came out in 2016 and it's the largest randomized trial to date you know testosterone doesn't have a lot of randomized Trials 790 men older than age 65 with unequivocally low levels of testosterone treated with one year one year a placebo or one percent gel the benefits were not simply sexual meaning erections in libido but in that one year that short time we saw an improvement of physical Mobility mood energy bone density and strength but most of these benefits were dismissed as minor and not clinically significant foreign testosterone is a metabolic sexual and Vascular hormone that serves an important metabolic function and plays a key role in human physiology and health it improves the signs and symptoms of testosterone deficiency without serious AES and the tea trials and the testosterone for diabetes mellitus provided evidence that testosterone therapy in older men improves sexual function mood ameliorates anemia of known and unknown causes and it improves bone mineral density and Bone strength and it may indeed reduce fracture risk and Fracture rate in men and it's associated with a reduced risk of vascular and overall mortality and Low T is associated with an increased incidence of dementia and Alzheimer's disease so what are the facts and what are the levels of evidence it improves sexual function modestly it may improve mild to moderate depression it improves bone mineral density muscle and reduces fat Mass it improves strength and exercise endurance it may reduce cardiovascular mortality and all-cause mortality within six months we're going to see the results of the Traverse study which is five years of testosterone gel versus placebo in 3 000 men with low levels and at least one symptom and with the Type 4 diabetes mellitus study we see the benefits of testosterone therapy in preventing type 2 diabetes equivalent to metformin so this is a randomized double bind placebo-controlled two-year phase 3B trial involving six Australian tertiary centers enrolling men with low levels these men had were not hypogonadal per U.S standards their levels were below 400. and they all had visceral adiposity and the aim was to determine whether testosterone therapy prevents progression to or reverses type 2 diabetes beyond the effects of standard lifestyle so you had abduct these men all had visceral adiposity they were aged between 50 and 74. their levels were below 400 and they were at risk or had type 2 diabetes they were randomized to either a lifestyle plus testosterone and decino8 every 12 weeks the long-acting or Placebo and lifestyle and what you saw was that testosterone therapy plus lifestyle significantly reduced the prevalence of type 2 diabetes versus lifestyle intervention alone and it decreased the prevalence of type 2 diabetes by almost 41 versus placebo what we see is that among men with low levels and at high risk for type 2 diabetes these were men who had abnormal glucose tolerance tests testosterone therapy and lifestyle prevented progression to type 2 diabetes in twice as many cases versus lifestyle alone and these again were men with low levels you saw the that among men with low levels and type 2 diabetes that reversed type 2 diabetes and over 10 percent more cases than lifestyle alone and that testosterone perhaps restored insulin sensitivity we don't know exactly the mechanism for this what about testosterone and prostate cancer Stacy Loeb at NYU found in a national prostate cancer registry that patients who receive testosterone therapy had a lower risk of aggressive prostate cancer than those who did not and we've known for a long time that men who are hypogonadal have more aggressive prostate cancer than men who are you gonadal found in hypogomanal men following radical prostatectomy that cancer recurred in 7.2 percent of men receiving testosterone therapy versus 12.6 percent of men who did not the recurrence rate was 50 percent lower and in bipolar Androgen therapy which is done used to treat metastatic castrate resistant prostate cancer Sweitzer found in 14 men treated with high-dose testosterone injections every four weeks while on ADT resulted in superficial physiologic levels of testosterone followed by castrate levels and demonstrated a 50 reduction in PSA so patients receiving that reported significant Improvement in quality of life fatigue and sexual function and most recently Hudson in Lancet longevity reviewed 35 placebo-controlled Trials of trt 5600 male participants and had individual participant data there was no significant increased risk of cardiovascular events between testosterone therapy and Placebo and this is the largest individual analysis of tea trials to date the UK biobank 160 000 men median age of 61. 826 developed dementia and 288 developed Alzheimer's disease the lowest testosterone total testosterone levels were associated with the highest dementia quintile so a lower testosterone and a higher shbg are independently associated with incident dementia and Alzheimer's disease and is male hypogonalism a risk factor for hospitalization from covid Sandeep dehinsa at washu looked at 723 men and published in Jama um mean age 55 116 of these men had hypogonadism and 147 were you going out 180 received testosterone therapy men with hypogonadism were more likely than men with eugonadism to be hospitalized with covet 19. and you can see on this graph that those men with lower levels had a much higher rate of hospitalization and a much higher rate of being in the ICU and men who received inadequate testosterone therapy to find a subnormal concentrations had higher odds of hospitalization compared to men who had normal levels so Men's Health and what I do and when I try to have done that are centers and sexual medicine are correlated across all major chronic disease areas and they impact men across all racial and ethnic and social economic and geographical boundaries and that's what's part of the metabolic or cardiometabolic workup um Mark way had always said you have to have a puppy slide so this is my puppy's I wanted to talk briefly two minutes about erectile dysfunction because we're going to have a very important meeting in March um known as the Princeton four guidelines this was a lifestyle study published by Dean ornish and Robert ostfield and other cardiologists looking at erectile dysfunction and the iaf score increase on an average of four which is the same level as oral pd5 therapy in a very very intense exercise program and lifestyle mitigation the increase was likely mediated through weight loss and consuming a Mediterranean diet rich in plant-based Foods the Princeton 4 that I mentioned is being led by Ray Rosen and Robert cloner and it's going to look at potential benefits of pde5 Inhibitors and the algorithmic use of these potential Inhibitors are we going to have a poly pill of Statin and tidalophil for men to be taken on a daily basis with the addition potentially of losartan and ARB inhibitor so this was a study that came out this week by Bob cloner and Ray Rosen and they looked at the um were looking to determine the effect of pd5s on mace major adverse cardiovascular events they matched a multivariate analysis and they showed that mace was lower by 13 percent in 24 000 men exposed to pd5 therapy versus non-exposure and this was true for coronary revascularization with an overall lower incidence of 25 percent of mortality here you see over the past five years nine studies that also note a significant cardiovascular risk reduction in mace and mortality and it's up to 25 percent