Male Menopause, Low Libido and Testosterone Replacement - Transcript

Dr. George Papanicolaou (00:00): If you're just looking at testosterone alone, then you're going to potentially miss the root cause of the problem. So just replacing testosterone is never a good idea. Dr. Mark Hyman (00:16): Welcome to Doctor's Farmacy. I'm Dr. Mark Hyman and that's Farmacy with an F. F-A-R-M-A-C-Y, a place for conversations that matter. If you have had issues with hormones, this conversation is going to matter to you because it's with my colleague and friend at the UltraWellness Center, Dr. George Papanicolaou. Here we are at the UltraWellness Center in Lenox, Massachusetts. We're appropriately socially distanced and we are going to talk about a number of cases today, and one of them is going to be about hormones. It's a big issue. Dr. Mark Hyman (00:45): George has joined our practice a number of years ago. He's an incredible physician, a big man with a big heart. He's been a functional medicine practitioner for years. He worked on the Navajo Reservation, and he's just an extraordinary dude who I love having in our practice. We are going to talk about hormones today and all things hormones. So George, welcome to The Doctor's Farmacy podcast. Dr. George Papanicolaou (01:06): Mark, it's always a pleasure. Dr. Mark Hyman (01:08): So hormones is a big topic. Dr. George Papanicolaou (01:10): Right. Dr. Mark Hyman (01:12): And we talk about hormones in men, hormones in women, and there's a lot of hormones, right? There's sex hormones like testosterone, estrogen, progesterone. There's thyroid hormones, insulin, stress hormones, and there's many, many other hormones, but we're going to focus today on guys who have a problem that's very common, sometimes referred to in the media as low T or low testosterone, which is a pandemic out there and it causes so many different issues. Other people call it andropause or male menopause, but if you're a guy listening to this, whether you're 30 or 40 or 50 or 60, this could be happening to you and you just don't know it- Dr. George Papanicolaou (01:53): Absolutely. Dr. Mark Hyman (01:53): ... and it makes you feel like crap. You are often misdiagnosed, misunderstood, and suffering with fatigue, muscle loss, low sex drive, and lots of other problems. So George, tell us a little bit about how we think about this in traditional medicine and how that contrasts with how we approach hormone imbalances in functional medicine. Dr. George Papanicolaou (02:17): Well you hit all the hot spots. Dr. Mark Hyman (02:21): Did I steal your thunder? Dr. George Papanicolaou (02:21): Yeah, yeah, yeah. Again, I mean it's ... Yeah, he stole my thunder. Yeah, you hit all the hot spots. Men, when we think about hormone replacement, we're always thinking about women, but believe it or not, I have more men asking me about hormones than I do women. I think there's some reasons behind that. I think women still have a great deal of fear about hormones because the media for so many years would publicize the relationship between hormones and cancer. So women are very reluctant. Men on the other hand are now starting to experience hormone issues and it's becoming more of a popular conversation. As you said, the media talks about it and men are living longer and they're starting to experience difficulties with all the things you just said: fatigue, mental disclarity, brain fog- Dr. Mark Hyman (03:19): Lack of motivation. Dr. George Papanicolaou (03:19): ... libido, lack of motivation- Dr. Mark Hyman (03:21): Energy. Dr. George Papanicolaou (03:21): ... erectile dysfunction. They want to get help with that. Why shouldn't they? We want to live vital lives. The difficulty is in the diagnosis. So that's where we run into our first difficulty. Dr. Mark Hyman (03:34): So how is this treated in traditional medicine or is it? Dr. George Papanicolaou (03:37): Well that's the point. The diagnosis piece, it's really ... The diagnosis requires you to have low testosterone of about 250 to 300. Dr. Mark Hyman (03:47): Which is about what you see in the average 97-year-old. Dr. George Papanicolaou (03:50): Exactly. Yeah, exactly. Exactly. So now, a gentleman shows up with a- Dr. Mark Hyman (03:56): What's a normal for a guy who is like 20, 30? What's that- Dr. George Papanicolaou (03:59): I mean he can be anywhere from 600 to 1000. Dr. Mark Hyman (04:01): Yeah. Dr. George Papanicolaou (04:02): So a guy shows up with a testosterone of 400, but he's not feeling good, he's tired, he has no sense of wellbeing, he doesn't have erections, he doesn't have motivation, he's apathetic, and his testosterone comes back at 400 and the doc says, "Hey, you know what? That's pretty good for a guy who's 52 or a guy who's 48." Dr. Mark Hyman (04:20): What do you expect for a guy your age? Dr. George Papanicolaou (04:21): Exactly. So that's the first problem. You don't treat the number. You treat the patient. That's where I think we really focus on in functional medicine. Then the second problem is that when you do address testosterone, that's all that gets addressed. Let's just replace your testosterone. That's not how you approach it in functional medicine, certainly not in my approach. For me, it's all about the first thing we do is we dig into lifestyle because if you change lifestyle, most of the time I can get that testosterone to get up to 600 just by changing lifestyle and addressing some comorbidities that might exist. Dr. Mark Hyman (05:04): So let's talk about that. What are the drivers of dropping testosterone in guys from a lifestyle perspective and what do you do to address those? Dr. George Papanicolaou (05:12): Stress, nutrition, lack of exercise, poor sleep, too much alcohol, too much pot, bad relationships. Dr. Mark Hyman (05:23): The usual suspects? Dr. George Papanicolaou (05:24): Yeah, yeah. Dr. Mark Hyman (05:26): So you said stress lowers testosterone? Dr. George Papanicolaou (05:28): Yeah, it does. Dr. Mark Hyman (05:30): My favorite study was this study where they looked at guys who went to football games and they measured their testosterone before and after the game. Dr. George Papanicolaou (05:39): I know this study. Dr. Mark Hyman (05:40): And the guys whose team won, their testosterone levels went up. The guys whose team lost, their testosterone levels went down. Dr. George Papanicolaou (05:48): Particularly the ones that had been gambling. Dr. Mark Hyman (05:49): Oh, the ones that had been gambling, I didn't catch that part. That was in the fine print in the methods of the study. I didn't get that. Dr. George Papanicolaou (05:56): Right. Dr. Mark Hyman (05:56): That is striking when you think about that. Dr. George Papanicolaou (05:58): Yeah. Dr. Mark Hyman (05:58): So your mental state has a huge effect on your hormones. Dr. George Papanicolaou (06:02): Yeah. Dr. Mark Hyman (06:03): So you mentioned also nutrition. Talk about that because I think that's something people understand. How does food affect your hormone levels, particularly testosterone? Dr. George Papanicolaou (06:11): Well food is fundamental to ... It's the building blocks for everything that we need. So hormones require certain food macronutrients. You need really good healthy fats so that you can have cholesterol in your system so you can make ... Because cholesterol is the building block for testosterone. So diet provides us the macronutrients we need to be the building blocks for creating hormones. Cholesterol is a building block. Dr. Mark Hyman (06:37): So cholesterol is what actually testosterone is made from? Dr. George Papanicolaou (06:39): Yes. Right. Dr. Mark Hyman (06:40): So what about people taking statins? Dr. George Papanicolaou (06:42): They could potentially ... Statins can lead to low testosterone because you're going to drop your cholesterol levels and if you get them too low, you're not going to have that building block. If you're under lots of stress and if you're not sleeping well, both of those are going to drive down your, are really going to create, we'll get to this later, an imbalance where you're going to actually produce too much cortisol which is going to demand the use of cholesterol because cortisol is also made from cholesterol. So you have this sink of cholesterol and it needs to be used to make your hormones, and if you're using it primarily to make cortisol- Dr. Mark Hyman (07:23): Like the cortisol steals it away. Dr. George Papanicolaou (07:25): Cortisol steal, it steals it away from being able to make testosterone. So getting back to the nutrition piece, we do need those building blocks that come from eating fatty fish, taking a fish oil capsule if you don't, and then making sure you have all the other nutrients that are required to make testosterone. It's very important. Dr. Mark Hyman (07:43): What about what causes it to go down? Because that's what causes it to go up. In fact, saturated fats can help it go up. Dr. George Papanicolaou (07:50): Right. Exactly. So what causes it to go down? Dr. Mark Hyman (07:55): Yeah. Dr. George Papanicolaou (07:55): Sugar plays a big role in creating inflammation. Sugar also will drive insulin up and that can have an impact on your testosterone levels as well. So having a diet that's going to be rich in whole foods, low in sugars, processed foods will definitely be beneficial. Dr. Mark Hyman (08:15): So essentially what you're saying is that our diet plays a huge role in regulating our hormones. Dr. George Papanicolaou (08:20): Oh, yeah. Dr. Mark Hyman (08:21): So good fats are good for you- Dr. George Papanicolaou (08:23): Yeah. Dr. Mark Hyman (08:23): ... and even a little saturated fat is necessary to- Dr. George Papanicolaou (08:25): Absolutely. Dr. Mark Hyman (08:25): ... to produce cholesterol. Our starchy, sugary diet which is about a pound a day per person in America of starch and sugar which basically are the same interchangeable- Dr. George Papanicolaou (08:34): Yeah. Dr. Mark Hyman (08:35): ... flour and sugar, drives your testosterone down. Dr. George Papanicolaou (08:38): Absolutely. Dr. Mark Hyman (08:39): When you get high insulin levels from eating too much starch and sugar, that causes the deposition of belly fat. So what you see is this amazing phenomenon where these guys, they get these big bellies- Dr. George Papanicolaou (08:52): Yeah. Dr. Mark Hyman (08:52): ... their testosterone goes down, they lose hair on their body, and they actually get man boobs. Why does that happen? Dr. George Papanicolaou (09:02): Yeah, because what's happening is that when you have that excess belly fat, it's basically too much estrogen. Estrogen ... When I talk about my case, we're going to talk about this. When you have too much estrogen, then estrogen drives something called sex hormone binding globulin. So this is a protein that carries your testosterone throughout your body, but the active testosterone is free. It's not bound. So when you drive your estrogen levels up, then you're going ... By being overweight, you're going to store excess estrogen in that belly fat. Then what's going to happen is that you're going to then drive up your sex hormone binding globulin, you're going to bind that free testosterone, and now you're going to start to experience the effects of low testosterone. Dr. Mark Hyman (09:55): Yeah, and also estrogen gets ... Testosterone gets converted to- Dr. George Papanicolaou (09:59): Converted to estrogen. Dr. Mark Hyman (09:59): ... estrogen. Dr. George Papanicolaou (10:00): Right. Dr. Mark Hyman (10:00): There's ways to block that conversion. Dr. George Papanicolaou (10:02): There are. Dr. Mark Hyman (10:03): But the key is it's so diet-related. Dr. George Papanicolaou (10:05): Yeah. Dr. Mark Hyman (10:05): So maybe getting your sexual function back has to do with getting your belly to go down- Dr. George Papanicolaou (10:11): Absolutely. Dr. Mark Hyman (10:12): ... if you want something else to go up. Dr. George Papanicolaou (10:13): Yeah. It's so true. What happens to men in our society is that they're working too hard, they're stressed out, they don't sleep well. Then they eat in such a way that they're going to gain weight. All of those things are impacting their testosterone levels, but there's this combination too where cortisol as we talked about is going to steal. You lose your testosterone there, but also you begin to have other hormones that are involved. So if you're again ... We're going to talk about this in the case. If your thyroid isn't functioning well, there are some studies that show, and it wasn't really clear to me as I looked at the studies and I don't think that they delineated it, but when you have hypothyroidism, you can also have low testosterone. So you have to look at all, you have to look at all the hormones. Dr. Mark Hyman (11:05): Low sexual desire is one of the symptoms of- Dr. George Papanicolaou (11:05): Yeah. Dr. Mark Hyman (11:05): ... low thyroid. Dr. George Papanicolaou (11:08): Yeah, so you have to look at ... When you think about testosterone in men when they come in saying, "Hey, I think my testosterone's low or I'm having erectile function issues or I just can't build muscle mass in the gym," I think about testosterone, but I think about balancing all the other hormones. I start to look at the entire lifestyle package. Dr. Mark Hyman (11:30): Well they're all connected, right? Dr. George Papanicolaou (11:31): Absolutely. Dr. Mark Hyman (11:31): It's like a big chicken wire. Insulin, sex hormones, cortisol, they're all interchangeable and they're all- Dr. George Papanicolaou (11:38): They're all interchangeable. Dr. Mark Hyman (11:39): ... separated by a few different molecules that are regulated by different enzymes. It's like a pinball machine and which ones are going to go down and you don't know. Dr. George Papanicolaou (11:48): If you're just looking at testosterone alone, then you're going to potentially miss the root cause of the problem. So just replacing testosterone is never a good idea. Dr. Mark Hyman (12:00): And alcohol is another huge factor. When you see guys who drink and have "beer bellies," what happens to their bodies? Dr. George Papanicolaou (12:06): Right. Dr. Mark Hyman (12:07): They get this big belly. They get breast enlargement. They lose all the hair on their bodies so they look more like women. It's because the alcohol increases estrogen production in the body. Dr. George Papanicolaou (12:18): Right. Dr. Mark Hyman (12:18): That's why alcohol increases the risk of breast cancer, but it has that effect in men as well and when you help them cut out the alcohol, cut out the starch and sugar- Dr. George Papanicolaou (12:26): Right. Dr. Mark Hyman (12:26): ... increase the good fats, increase fiber, increase plant-rich diet, these guys see dramatic improvements in their hormone levels without actually using medication. So that's always the first step, addressing these lifestyle factors, sleep, stress, exercise, diet, and sugar, alcohol. Dr. George Papanicolaou (12:44): Right. Dr. Mark Hyman (12:45): The other thing that is fascinating is muscle is playing a huge role. One of the ways to boost testosterone- Dr. George Papanicolaou (12:51): Is to exercise and build muscle. Dr. Mark Hyman (12:52): Yeah, strength training literally will build your muscle- Dr. George Papanicolaou (12:55): Absolutely. Dr. Mark Hyman (12:56): ... and will build your testosterone levels. Dr. George Papanicolaou (12:58): Yeah. So when we're talking about patients with low testosterone, it's always lifestyle first and managing all of that. So we're going to ... The first things I'm going to do with my patients are the things that we're already discussed and it's going to be get them exercising again, get them meditating to reduce their stress and the cortisol levels, get them to avoid alcohol as much. You know what? That's not what they come in. They don't come in for me to tell them to do that. Dr. Mark Hyman (13:25): No. Dr. George Papanicolaou (13:25): They want the magic. Dr. Mark Hyman (13:27): Yeah. Dr. George Papanicolaou (13:28): They want the testosterone injection or testosterone gel. That's not where I start. In the end for a majority of the men that I work with, they're much happier because my changing all their lifestyle factors, they're much more satisfied and they're much healthier- Dr. Mark Hyman (13:47): There's a lot of beneficial side effects. Dr. George Papanicolaou (13:49): Huge side effects to improving all of those things. Dr. Mark Hyman (13:52): Like weight loss, increased energy, better sleep, happier, all of that stuff. Dr. George Papanicolaou (13:57): Oh, just by getting them to meditate, I very much believe in the benefits. The data on meditation and its impact on your body, your overall health is huge. So I've probably, every male patient that comes into my practice has that conversation with me and they're just shocked that we're talking about meditation. When they come in for all the issues they come in with and I identify stress is a major issue and I tell them about meditation, that will drive their cortisol down and that will help them improve their testosterone levels in and of itself. Dr. Mark Hyman (14:31): Hey, everybody. It's Dr. Hyman. Thanks for tuning into The Doctor's Farmacy. I hope you're loving this podcast. It's one of my favorite things to do and introducing to you all the experts that I know and I love and that I've learned so much from. I want to tell you about something else I'm doing which is called Mark's Picks. It's my weekly newsletter and in it, I share my favorite stuff from foods to supplements to gadgets to tools to enhance your health. It's all the cool stuff that I use and that my team uses to optimize and enhance our health. I'd love you to sign up for the weekly newsletter. I'll only send it to you once a week on Fridays. Nothing else, I promise. All you have to do is go to to sign up. That's, P-I-C-K-S, and sign up for the newsletter and I'll share with you my favorite stuff that I use to enhance my health and get healthier and better and live younger longer. Now, back to this week's episode. Dr. Mark Hyman (15:27): So tell us about this patient you had who came in with fatigue and he was overweight. What was the story with this patient and how did you approach him? Because functional medicine is a very different approach. Like you said, it's not just, "Here, take the testosterone." It's looking at all the variables that could be impacting a patient and affecting their hormones, whether it's toxins, whether it's their gut, whether it's nutritional deficiencies, whether it's their diet, stress, all these factors that we look at comprehensively in functional medicine. That's what we do at the UltraWellness Center. That's why we have so much success because we're not just, "Oh, you have low testosterone? Give testosterone." It's a comprehensive approach- Dr. George Papanicolaou (16:04): Right. Dr. Mark Hyman (16:04): ... because of all these variables. Dr. George Papanicolaou (16:05): Right. So this gentleman came in. He was experiencing fatigue. As you described already, he was having adiposity around his waist and also in his breast tissue and he had been working out. He'd already been to a physician who had given him testosterone and he was not getting the clinical benefit that he wanted. So when a patient like that comes in, we begin to go through everything. We go through the lifestyle, we go through previous treatments, and we go around our matrix which is that tool that we use that identifies the way we think about overall health in a patient. We don't treat the symptoms. We treat the systems. Dr. George Papanicolaou (16:48): So in this particular patient, I immediately identified that he was a busy executive, 52 years old. He was under stress. He was a little bit overweight. He had been on testosterone and he brought me some lab values, and his testosterone had gone up, but his free testosterone was really low. Dr. Mark Hyman (17:09): That's the active testosterone. Dr. George Papanicolaou (17:11): That's the active testosterone. So I started to think- Dr. Mark Hyman (17:14): So in other words, you're saying that a guy could have a normal level. If the doctor ... Let's say you check the normals. Let's say 300 to 1000. Dr. George Papanicolaou (17:20): He was about 550. Dr. Mark Hyman (17:21): So he's 550 which seems pretty good, but if you don't check the level of active free hormone, you're not really knowing what's going on. Dr. George Papanicolaou (17:29): Right. Dr. Mark Hyman (17:29): If you don't check these other tests you're going to talk about- Dr. George Papanicolaou (17:31): Right. Dr. Mark Hyman (17:32): ... you don't really know what's going on. So tell us about how that works. Dr. George Papanicolaou (17:35): Yeah, so when you see that, you're like, "Well that's interesting." So the tests that I do included something called a Dutch profile. A Dutch profile, that just doesn't tell me about the total amount of testosterone. It also tells us how you metabolize your testosterone. As you mentioned earlier, Mark, that you convert your testosterone to estrogen and there are some men that naturally convert their testosterone very efficiently, too efficiently into estrogen so they're over-aromatizing. You can see that on the Dutch profile. You can see the results show you that pattern. He was an over-aromatizer. So when he was being given testosterone, he was converting a lot of it into estrogen. Dr. Mark Hyman (18:26): So he was actually taking testosterone? Dr. George Papanicolaou (18:28): Yeah, at the time. Dr. Mark Hyman (18:29): He came in with testosterone? Dr. George Papanicolaou (18:30): He was taking testosterone when he came in and he'd actually gained more visceral fat while he was taking it. Dr. Mark Hyman (18:37): So it sort of backfired. Dr. George Papanicolaou (18:38): Yeah, it backfired. Dr. Mark Hyman (18:38): Testosterone is supposed to build muscle. Dr. George Papanicolaou (18:40): This is very interesting. That's why I brought up this case. [crosstalk 00:18:43]. Dr. Mark Hyman (18:44): If you just go to regular, traditional doctor- Dr. George Papanicolaou (18:45): Exactly. Dr. Mark Hyman (18:46): ... meaning to get testosterone, they'll just give you testosterone. They won't look at all these- Dr. George Papanicolaou (18:49): Right. Dr. Mark Hyman (18:49): ... other variables and like, "Well I don't know why you're losing muscle and gaining fat and growing boobs and losing hair on your body." Dr. George Papanicolaou (18:55): Right. So it was an interesting case because what hadn't been tested was his sex hormone binding globulin hadn't been tested and his estrogen had not been tested, and he'd been on the testosterone for almost nine months and he saw these differences. So on the basic labs that anybody can get, I checked his estradiol level, I checked his sex hormone binding globulin, and his estradiol level relative to testosterone was elevated, his sex hormone binding globulin was also elevated, and that's what was binding the free testosterone. Then when I looked at his Dutch profile, it all made sense. He was an over-aromatizer. Dr. Mark Hyman (19:34): So this Dutch profile is a test we do at the UltraWellness Center- Dr. George Papanicolaou (19:36): Yeah. Dr. Mark Hyman (19:36): ... that's quite different. It looks at how all these hormones interact- Dr. George Papanicolaou (19:39): Correct. Dr. Mark Hyman (19:39): ... how they're metabolized, what's getting converted to what, where the imbalances are. This is not something you get with traditional hormone tests that you go to the lab and get. Dr. George Papanicolaou (19:47): Right. Dr. Mark Hyman (19:48): It's a saliva test. Dr. George Papanicolaou (19:49): Exactly. It's a saliva test and it's a very effective test and it made sense when I saw that picture. So that's the difference. Now, he had some other things going on that included his sleep apnea, but the main thing was that all we needed to do was address this hormone imbalance. To do that, we needed to account for the fact that he didn't aromatize really well. So you add in something, an aromatase inhibitor called anastrozole. So I added anastrozole to his treatment plan and that was going to make a difference. Now, that was going to block his body's natural ability to so readily turn testosterone into estrogen. Dr. George Papanicolaou (20:36): Because of his age and the urgency because he was getting a lot of emotional stress over this, I added in a peptide. So I added in something called CJC1297 and that actually helps you along with [ipamorelin 00:20:56], that combination will help you lose fat and gain muscle. So we added that in for three-month cycle. He did extraordinarily well. He lost all that visceral adiposity around his waist, also the man boobs went away, and he was feeling great, gaining muscle mass, and was extraordinarily pleased with the outcome. Dr. Mark Hyman (21:18): Amazing. So you talk about this anastrozole which is a medication. It's used often in cancer treatment- Dr. George Papanicolaou (21:25): Right. Dr. Mark Hyman (21:26): ... for women for breast cancer- Dr. George Papanicolaou (21:27): Right. Dr. Mark Hyman (21:27): ... because it blocks estrogen production by the body. There are also natural ways to inhibit aromatase and to help with the excess estrogen. One of the ways that we deal with hormone imbalance is using foods- Dr. George Papanicolaou (21:41): Right. Dr. Mark Hyman (21:41): ... and using even ingredients that are in foods that are powerful regulators of hormones. One of the most important things is a compound found in the broccoli family, the brassica family. Dr. George Papanicolaou (21:52): Right. Dr. Mark Hyman (21:52): It's called [diendomethane 00:21:54] or DEM. Dr. George Papanicolaou (21:55): Right. Dr. Mark Hyman (21:55): That can be used in patients who are taking testosterone to help effect the hormone metabolism into estrogen and limit that. Dr. George Papanicolaou (22:03): Absolutely. Dr. Mark Hyman (22:04): You can also use biotin. Dr. George Papanicolaou (22:05): Right. Dr. Mark Hyman (22:06): So there's a lot of other things that can be taken- Dr. George Papanicolaou (22:08): Yeah. Dr. Mark Hyman (22:09): ... along with the hormone replacement to help mitigate- Dr. George Papanicolaou (22:12): And I will commonly use DEM and calcium [glucarate 00:22:15] because they both increase the metabolism of estrogen. I use them in women, but I also use them in men, particularly gentlemen like this. That would have been an option. I chose to do something that would be a more aggressive- Dr. Mark Hyman (22:28): Yeah, this is- Dr. George Papanicolaou (22:28): ... approach. Dr. Mark Hyman (22:29): ... definitely going to work faster. Then what about the method of testosterone replacement? Can you talk about the options for men about what kinds of available testosterone replacements there are and what is the point at which you would initiate that? What's your decision on these patients of, "Okay. This is now the time to start?" Dr. George Papanicolaou (22:47): Right. So the first thing I do is I as I said before, we balance out everything else. We do lifestyle factors and we make sure that that's all in place. If after six months or so of lifestyle factor intervention they're not improving, that's when we'll start talking about testosterone replacement. Testosterone replacement, you can do topicals, you can do injectables, and I tend to use the injectables because they're very effective and very efficient. Dr. Mark Hyman (23:18): So how did that work? How do you do an injection? Dr. George Papanicolaou (23:20): So injectables can be given IM, but recently- Dr. Mark Hyman (23:23): In the muscle. Dr. George Papanicolaou (23:24): Which is in the muscle and recent research has shown that [subQ 00:23:27] injection, meaning you just pinch the little fat around your waist, you inject right into that little piece of tissue that you have there. That's called a subQ injection. You can get absorption and elevation of testosterone just as effectively as IM. So it's a very, very simple- Dr. Mark Hyman (23:44): And that's an easier procedure. Dr. George Papanicolaou (23:45): Oh, it's very simple. Dr. Mark Hyman (23:46): And you use compounded hormones? You just get them at the regular pharmacy? Where do you get them? Dr. George Papanicolaou (23:50): So you can get them at a regular pharmacy and you can get them compounded. Most of the time, the raw ingredient of testosterone is going to be very similar. It's the carrier molecule that might be different. So some pharmacies use grape seed oil. I mean some compounding pharmacies use grape seed oil because there's some theoretic advantage of absorption. So when they compound it, it's going to be the same raw material. It's going to be the carrier that might be different. So I use compounded when that's appropriate. Sometimes patients don't want compounded. It's a little bit more expensive. So we'll go with a pharmaceutical grade from the local pharmacy. Then we'll do subQ injections. Dr. Mark Hyman (24:34): What about the topicals? Can you talk about when you would decide to use topicals or why or not? Dr. George Papanicolaou (24:40): I don't use topicals that often. The reason being is that they're just sloppy. I'll just say you need to use large quantities of them to get the concentration that you need. You need to be sure to wash your hands after you've used it because you can actually, by touching your child or touching your wife, they can actually absorb some of that testosterone. I've had situations where women are beginning to have the effects of elevated testosterone because they're coming in contact with their husband's testosterone on their shoulder or what other location you may have placed it or if he didn't wash his hands appropriately and they're in intimate contact. So I don't use gels that often. Because you can do subQ injections, I primarily use the subQ injectable form of testosterone. Dr. Mark Hyman (25:31): And there's other forms, right? Pellets. Can you talk about that? Dr. George Papanicolaou (25:34): You can do pellets. So again, pellets- Dr. Mark Hyman (25:37): What is that? How do you do it? Dr. George Papanicolaou (25:38): So they have to be placed under your skin and they're usually placed for up to six months. They get replaced. The issue ... Well there's no issue with pellets. They work fine, but you don't have the ability to make any alterations in the testosterone concentrations. So if it's not enough, they're not experiencing it, you have to remove them, you have to put new pellets in. I find that using testosterone injectable is just very flexible and it's very, very simple and easy and it doesn't involve the placing of pellets in the skin. Dr. Mark Hyman (26:14): Yeah. In terms of the side effects of testosterone replacement because it is a hormone and it can have adverse effects and there's concern about risk of prostate cancer, high cholesterol, heart disease, how do you address that? Dr. George Papanicolaou (26:32): Well I think the data on all of those are mixed. When you look at heart disease particularly in relationship to metabolic syndrome and even diabetes, actually taking ... If you have low testosterone which you probably will have in those cases, actually there are studies that show replacing testosterone will improve your metabolic syndrome, will actually improve your glycemic control. Dr. Mark Hyman (26:58): Because it improves muscle mass and blood sugar, yeah. Dr. George Papanicolaou (27:00): Exactly. So in that regard- Dr. Mark Hyman (27:03): But it can spike people's cholesterol. Dr. George Papanicolaou (27:05): You can. You can spike people's cholesterol. Dr. Mark Hyman (27:08): Does that mean they need a statin? Dr. George Papanicolaou (27:09): No, it does not mean they need a statin. It's not something ... You can also ... I've seen some studies where it also lowers cholesterol. So it's something I watch closely. It's not something I see that often. The other concern about prostate cancer is it's pretty clear in the data that testosterone does not cause prostate cancer. If you have prostate cancer, it can ... It's not something you want to be taking because it can accelerate the growth of the cancer. The issue that may ... Go ahead. Dr. Mark Hyman (27:42): No, I've talked to some urologists at Harvard and specialists in prostate cancer and a lot of times after prostate cancer treatment, men have low sexual function. They're actually using- Dr. George Papanicolaou (27:55): Absolutely. Dr. Mark Hyman (27:56): ... testosterone replacement in some of these men when they're carefully monitoring them. Dr. George Papanicolaou (27:58): Yes, absolutely. I've read that in the literature as well. So there's a lot of safety behind testosterone. That's why I think men are beginning to understand it's safer and they know it's an option and they want it. Particularly when you start to combine it with the lifestyle changes and you combine it with the use of peptides which I mentioned, men can regain a huge amount of vitality and really improve their overall experience of life in a very, fairly safe way. There's no reason ... I believe that as we age, things happen to our bodies that we should and can account for. I think it's a pretty low-hanging fruit for men to address these hormone issues and use things like peptides that are [secretagogues 00:28:49] for hormones that can actually increase muscle mass and decrease body fat as they're aging. Dr. Mark Hyman (28:58): Yeah, I think it's a really important point, George. We are living longer although our life expectancy is going down as a country because of all the obesity and terrible disease, but we are seeing people living longer lives. Sometimes in order to live vital lives, there needs to be a little bit of extra support because we do decline as we age, but there are ways to mitigate that through the lifestyle interventions. Exercise is so important. Building muscle is so important. That's why testosterone is so critical. Even for women, testosterone is very important. I think that affects their sexual function, affects their muscle mass, energy, motivation- Dr. George Papanicolaou (29:34): Absolutely. Dr. Mark Hyman (29:35): ... mood, and it's really an ignored aspect of hormone therapy in women. They think it's just estrogen and progesterone, but women also need this. I have many patients who use topical testosterone for women on the clitoris here at the UltraWellness Center. I mean we don't apply it directly. They do it themselves, but it's a very powerful treatment and it works. I know it works because women are always calling back for refills. They're just happily referring all their friends for it. So I think that's a lot of ways to use hormones judiciously to do the right amount. It's different than when we think of the anabolic steroids like testosterone that bodybuilders use. They use super physiologic doses. They use doses far beyond what is ideal for a normal level. You don't want to get super levels. You want optimal levels. Dr. George Papanicolaou (30:19): Optimal levels. Right. You want to make sure you're checking everything. I always check the sex hormone binding globulin. I always check the estrogen levels just to find a gentleman like this that really needed an adjustment, needed to be on an aromatase inhibitor. There are some docs that just put you on an aromatase inhibitor right with the testosterone. Dr. Mark Hyman (30:42): Yeah, I usually do the natural versions. Dr. George Papanicolaou (30:45): Right. You use DEM. Dr. Mark Hyman (30:46): I use DEM which is a supplement. Dr. George Papanicolaou (30:48): Right. Dr. Mark Hyman (30:48): And I use biotin. Dr. George Papanicolaou (30:49): Yeah. Dr. Mark Hyman (30:50): The other thing that I think is worth mentioning is that for some people, there's an increased conversion to something called DHT which is a dihydrotestosterone that can happen when you use hormone replacement therapy. Dr. George Papanicolaou (31:02): Right. Dr. Mark Hyman (31:02): That increases the size of the prostate. So people are concerned about enlarged prostates with this or it can also increase cancer risk in some patients. Dr. George Papanicolaou (31:11): Yeah. Dr. Mark Hyman (31:12): So it's really about looking at everybody's individual hormones, and there are natural ways to affect the dihydrotestosterone too. Dr. George Papanicolaou (31:19): Right. So with DHT in particular, that also ... And this is one of the concerns for women, hair loss. You have increased DHT which can affect the hair follicles and that can lead to hair loss. Dr. Mark Hyman (31:36): That's why men get hair loss and that's some of the drugs like Propecia- Dr. George Papanicolaou (31:40): Right. Dr. Mark Hyman (31:41): ... are actually blocking DHT- Dr. George Papanicolaou (31:42): Right. The five alpha reductase inhibitors. Dr. Mark Hyman (31:44): Yeah, to prevent the hair loss. Dr. George Papanicolaou (31:46): Right. Right. So that's I'm generally, again, careful about that. On the Dutch profile, it measures DHT so we can actually see if a person is going to be making too much of that and we can make adjustments. As you've brought up before, there are things that we can use like Propecia. Now, Propecia has some concerns in regards to some side effects that can be permanent. So we're careful with using that. Dr. Mark Hyman (32:15): There's natural versions, right? Dr. George Papanicolaou (32:16): Yeah, there's natural- Dr. Mark Hyman (32:16): Saw palmetto. Dr. George Papanicolaou (32:17): ... ways like saw palmetto. Dr. Mark Hyman (32:18): Which is basically an herb that you can take that helps to mitigate that conversion. Dr. George Papanicolaou (32:22): Yeah, and you can use that topically as well as an oil. Dr. Mark Hyman (32:25): Yeah. Dr. George Papanicolaou (32:25): So I use testosterone in women both [clitorally 00:32:31] and as part of their overall gel or I'll create for them their cream, but I'm somewhat careful about it because of the hair loss. Dr. Mark Hyman (32:42): Yeah. Dr. George Papanicolaou (32:42): Because the women, the women that are coming in that need it are also going through menopause and they're naturally beginning to experience some of the natural aging that will thin out their hair and change their hair growth cycle. They're have shorter anogen phase. So you have to be careful with the addition of testosterone. Dr. Mark Hyman (33:01): Yeah, we've done a number of podcasts with Dr. [Bo 00:33:03] and others on hormone replacement and hormone issues in women- Dr. George Papanicolaou (33:06): Right. Dr. Mark Hyman (33:06): ... which are common, infertility, PCOS, PMS, menopausal symptoms, fibroids. All these are signs of hormone imbalance and they manifest differently obviously in women than in men, and we use a very similar approach of looking at sophisticated testing that helps us navigate what's going on, not just doing a simple regular blood test. Dr. George Papanicolaou (33:25): Right. Dr. Mark Hyman (33:25): At the UltraWellness Center and in functional medicine, we know how to think through the complexity of human biology and we can map out what's happening in each individual and it's not a one-size-fits-all treatment. So it's the right medicine at the right dose for the right person for the right amount of time, and it's really that personalization that is so key. Dr. George Papanicolaou (33:43): Right. Dr. Mark Hyman (33:44): I think we have the ability to do testing to look at all these things, not just testosterone, but free testosterone, sex hormone binding globulin, DHT, estrogen levels, the pathways, aromatization, the saliva levels. It's a very sophisticated way- Dr. George Papanicolaou (33:59): Yeah. Dr. Mark Hyman (33:59): ... of looking at things that allows us to really personalize the treatment, minimize the dose and the risk, but maximize the benefit. Dr. George Papanicolaou (34:06): Yeah, and again with this patient looking at the Dutch profile that we use, that also tells us about the adrenal glands. Dr. Mark Hyman (34:13): Yeah. Dr. George Papanicolaou (34:13): Again, he was a man that was under a great deal of stress with his work at that particular time, and you could see that when you looked at the adrenal function on his Dutch profile. You could see that his total cortisol levels were low, his free cortisol levels were low which were evidence of chronic stress. Dr. Mark Hyman (34:33): Yeah. Dr. George Papanicolaou (34:34): So we had that conversation. So I can replace his testosterone and I can do all these manipulations to make sure that it works right, but if I don't reverse his stress, I am not doing that man a service. Dr. Mark Hyman (34:46): That's right. Dr. George Papanicolaou (34:48): He will not feel well. So with him, we talked about meditation and we also gave him an adrenal supplement. These are herbs that are adaptogens that help the adrenals function better- Dr. Mark Hyman (35:00): Yeah. Dr. George Papanicolaou (35:00): ... and between functioning adrenals that got his cortisol levels appropriately up but not too high, taught him how to meditate, he was a far ... This guy was not just happy about his testosterone. He was happy about the new lifestyle that he was adopting because then he got into yoga. Right? Then he had a different community. Dr. Mark Hyman (35:21): Yeah. Dr. George Papanicolaou (35:21): A different community of new blood and new stimulation in his life brought him greater life satisfaction. Dr. Mark Hyman (35:29): Yeah, I think that's true. So just to recap, many people suffer from hormonal imbalances and guys tend to have declining hormones as they age and even young guys. Dr. George Papanicolaou (35:41): Right. Dr. Mark Hyman (35:41): I've seen young guys as young as- Dr. George Papanicolaou (35:42): Absolutely. Dr. Mark Hyman (35:42): ... 20 who eat a crappy diet, are stressed, have low testosterone levels and poor sexual function. So it doesn't mean this just happens to 70-year-olds. It can happen to anybody along the spectrum. Dr. George Papanicolaou (35:52): Absolutely. Dr. Mark Hyman (35:53): So I think it's really important to understand we take a comprehensive approach. We look at lifestyle. We look at the role of nutrition in hormones, exercise, stress, sleep, environmental toxins, and we look at a complicated panel of hormones that help understand what's happening for that person. Then we apply the first things first which is food and lifestyle, and then we can modify using nutritional supplements, herbs, and if we need to, we'll use hormone replacement therapy, but use the minimum- Dr. George Papanicolaou (36:20): Absolutely. Dr. Mark Hyman (36:20): ... dose possible applied in the safest way possible in a way that we track and follow. That's what's so unique about functional medicine. It's not just a knee-jerk response to, "Oh, you have low testosterone. Take this. You have hormones. Take this." It's really understanding the whole picture. Dr. George Papanicolaou (36:33): Yeah. Dr. Mark Hyman (36:33): That's what we do at the UltraWellness Center. That's what's so special about our practice. We have a group of incredible physicians, nutritionists, physician assistants who've been working together for a long time. We have probably over 60 years of collective experience in functional medicine, and now we're doing all virtual visits. People want to come virtually. They can do it on Zoom. It's great. You can come here if you want in person, but we are also now adapted to the new environment of telemedicine so it doesn't create a barrier to entry. We'd love to see you here. Share these stories with your friends and family. It's been great talking to you, George. Dr. George Papanicolaou (37:06): It's always a pleasure, Mark. Dr. Mark Hyman (37:07): We're going to be back again. You have the number two podcast on The Doctor's Farmacy which is amazing. Of all of you we've had, you're number two right below [inaudible 00:37:17] on aging. So congratulations on that. Dr. George Papanicolaou (37:19): Thank you. I appreciate it. Dr. Mark Hyman (37:20): I think you're just fabulous guy and physician- Dr. George Papanicolaou (37:23): Well thank you. Dr. Mark Hyman (37:23): ... and privileged to work with you. For those listening if you enjoyed this podcast, please share it with your friends and family on social media. Leave a comment. We'd love to hear from you and hear your story about hormones. Please subscribe wherever you get your podcasts, and we'll see you next time on The Doctor's Farmacy.