Philippe Isabelle is seen working in the lab on a confirmation of a testosterone test at the Richmond Olympic Oval in Richmond, British Columbia on October 21, 2009.

Philippe Isabelle is seen working in the lab on a confirmation of a testosterone test at the Richmond Olympic Oval in Richmond, British Columbia on October 21, 2009.

Men’s testosterone levels are believed to decline as a natural part of aging. Some prescription drugs as well as environmental and lifestyle factors might also play a role. But doctors are prescribing testosterone drugs at record levels. Between 2001 and 2011, hormone use by men over age 40 nearly quadrupled. There could be significant risks. Several recent studies show a higher rate of heart attack and stroke in older men taking testosterone. Many doctors say that for men with truly low testosterone, the benefits of hormone therapy outweigh the risks. A discussion on the safety of prescription testosterone.

Guests

  • Roni Caryn Rabin medical reporter who writes a regular medical consumer column that appears in The New York Times' science section.
  • Dr. Adriane Fugh-Berman director of PharmedOut, a research and education project at Georgetown University Medical Center; associate professor of pharmacology and physiology at Georgetown.
  • Dr. Harry Fisch clinical professor of urology and reproductive medicine, New York Hospital/ Weill Medical College of Cornell University.

Transcript

  • 10:06:53

    MS. DIANE REHMThanks for joining us. I'm Diane Rehm. Recent studies show a higher risk of heart attack and stroke in older men who use prescription testosterone. Last week, the FDA said it's reassessing the safety of the hormone. Joining me in the studio to talk about risks and benefits of using testosterone, Dr. Adriane Fugh-Berman of Georgetown University Medical Center.

  • 10:07:24

    MS. DIANE REHMJoining us from an NPR studio in New York, Dr. Harry Fisch of New York Hospital and Cornell University, and Roni Caryn Rabin, a journalist who covers medicine and health. I'm sure many of you will have your own thoughts, your questions. Join us on 800-433-8850. Send us your email to drshow@wamu.org. Follow us on Facebook or send us a tweet. And thank you all for being with us.

  • 10:08:00

    DR. ADRIANE FUGH-BERMANDelighted to be here.

  • 10:08:02

    REHMAnd, Roni Rabin, if I could start with you, tell us about these most recent studies regarding prescribing testosterone.

  • 10:08:16

    MS. RONI CARYN RABINThe study that came out last week that got everyone's attention said that heart attacks doubled in men who were 65 and over within 90 days of getting their first prescription of testosterone and nearly tripled in younger men who had had a history of heart disease also within that 90-day period. And it wasn't the first study. There have been other studies, observational studies, randomized controlled trials that were analyzed that have sent this signal as well. So this alarmed a lot of people.

  • 10:08:44

    REHMI would wonder why there are so many more people taking testosterone. What does the research tell us, Roni?

  • 10:08:59

    RABINWell, it's become a huge business. This has become a $2 billion business in the United States over the last decade or so. There's been an enormous amount of money pumped into advertising, not just advertising specific drugs, but these campaigns to raise awareness about a disease or a condition. And at this point, nearly one in 25 men in their 60s is taking testosterone. Use has nearly quadrupled among men 40 and over.

  • 10:09:32

    REHMAnd, Dr. Fugh-Berman, the question becomes what is the difference between the so-called Low T that we hear so much about on television and low testosterone?

  • 10:09:53

    FUGH-BERMANWell, Diane, the term low T was actually invented by pharmaceutical companies in order to broaden the market that was eligible to receive testosterone. So the condition is called Low T to consumers. Usually, with physicians, they call it late onset hypogonadism, but it's really different than true hypogonadism where somebody might have a pituitary tumor or was born without testes or with un-descended testicles, for example.

  • 10:10:27

    FUGH-BERMANSo there are instances in which somebody should have testosterone therapy. But normally, aging men should not be taking testosterone therapy. Not only are there the risks that Roni has discussed, but there's also no evidence of benefits, really. So it's really being over-promoted among normal men. The imputed benefits are not real, and the risks are very real.

  • 10:11:05

    REHMNow, turning to you, Dr. Fisch. I understand that Low T is talked about in terms of feelings of fatigue, loss of sexual drive, depressed moods. In a situation like that, how are you prescribing testosterone?

  • 10:11:33

    DR. HARRY FISCHWell, there's a couple of things I would -- Dr. Fugh-Berman was saying there are no studies that show a benefit. There are studies that show benefits of men who actually have low testosterone. And I agree with Dr. Fugh-Berman about, you know, people who have very low levels of testosterone, such as pituitary tumors or testicular problems, can benefit dramatically from medications.

  • 10:11:54

    DR. HARRY FISCHAnd there's no question about those people. The question occurs as men get older and if they have hypogonadism. Clearly, men who are getting older and are fatigued and have other issues, such as you just mentioned, may not need any medication. They may need other more natural approaches to treatment. But if they do have low testosterone, that's an indication, that's a red flag that something more serious is going on and needs to be addressed.

  • 10:12:21

    REHMHow rare, Dr. Fisch, are those individuals with a truly medical problem?

  • 10:12:31

    FISCHWell, there are quite a bit of people that have true medical problems that manifest with a low testosterone. For example, there was studies that show about 40 to 50 percent of diabetic men have low testosterone. Obesity is associated with low testosterone, as is chronic fatigue. Now, that doesn't mean -- I want to make a point here. That doesn't mean because they have diabetes, low testosterone, just treat the low testosterone, not the diabetes.

  • 10:12:55

    FISCHWe always tell people, you know, to change their lifestyles, diet, exercise, of course, in addition to sleeping more. For example, the number one cause of fatigue in young men and older men, ready for this, is lack of sleep. So the first thing we tell people is to sleep. Testosterone is made when men sleep. So in this country where we're sleeping five to six hours a night when we should be sleeping eight to 10 hours a night makes a big difference.

  • 10:13:20

    FISCHSo simple information like that, as well as dietary changes. But, unfortunately, a lot of men may not be able to make those changes and in many times, we do provide medication to help them along.

  • 10:13:33

    REHMDr. Fisch, going back to my original question, I'm wondering how frequently you prescribe testosterone.

  • 10:13:43

    FISCHWell, my practice is one where I do prescribe medications to increase a body's production of testosterone, and it -- is it rare? Well, it is not rare. As I said, 50 percent, about half of men who have diabetes have low testosterone. So but the importance is when you say prescribe testosterone, in my practice -- and I'm supposed to be the guru of testosterone therapy. That's what I'm known for in some respects.

  • 10:14:10

    FISCHAnd most of the patients that I treat I don't treat with testosterone and that's a very important distinction. Just like Dr. Fugh-Berman said, you know, some people who have very low testosterone and are clear indications for sure those people need testosterone shots or gels, but for the vast majority of the so-called late onset hypogonadism, I treat with lifestyle changes, basic information on diet, but also with a drug called clomiphene citrate. And probably 70 percent of my patients are on a medication that's a generic medication that allows the body to produce its own testosterone.

  • 10:14:47

    REHMAll right. Dr. Fisch, I want to ask Roni Rabin specifically about Viagra and Cialis. Were they somehow exonerated in these studies of testosterone?

  • 10:15:08

    RABINWell, the PLOS-1 study did compare the testosterone effects with Viagra effects, I mean, not directly. It was in a randomized clinical trial, and it did try to tease out whether this effect of the cardiovascular problems was due to a suddenly ramped up sex life perhaps, as opposed to the actual drug. And they did find that this was an effect of the testosterone, not the Viagra.

  • 10:15:36

    REHMAll right. And to you, Dr. Fugh-Berman, what about AndroGel?

  • 10:15:43

    FUGH-BERMANWell, I need to say that determining what low testosterone is, that's not actually established in medicine. That in studies that have looked at low testosterone, they've picked all kinds of different levels. Testosterone levels vary by lab. There's wide ranges of normal testosterone levels in every age group so while a group of 80 year olds will have lower testosterone that a group of 20 year olds, in every age group, there will be a very wide range. There's no connection between testosterone levels and symptoms, and all of these symptoms are quite nonspecific, of course, things like...

  • 10:16:20

    REHMSuch as?

  • 10:16:21

    FUGH-BERMANSuch as fatigue or diminished sports performance or diminished body hair. Some of the Low T tests asks, are you sad and/or grumpy? Everybody in my office failed the Low T quiz, including the 25-year-old women. But -- and that quiz was actually invented by a physician who was being paid by pharmaceutical companies and apparently wrote the quiz on toilet paper.

  • 10:16:53

    REHMBut what about the question of erectile dysfunction?

  • 10:16:58

    FUGH-BERMANOh, yeah, great question. So testosterone doesn't actually work for erectile dysfunction. So while there is evidence that testosterone increases libido, it does not increase sexual function, which just seems like a more frustrating situation to me.

  • 10:17:13

    REHMWhat does it do?

  • 10:17:15

    FUGH-BERMANWell, in very high doses, it has an effect on muscle. AndroGel and these other popular gels that are being used in people who aren't bodybuilders, it may not even do that. That's a little unclear, but in a study several years ago where testosterone gel was given to men over 65 because it was hoped that they could carry packages up steps faster and just walk around more easily, that study was actually stopped early because of increased cardiovascular events.

  • 10:17:49

    FUGH-BERMANSo it was stopped because the treatment was dangerous. As Roni has pointed out, there have been a number of studies now showing an increased risk of cardiovascular events with testosterone and those aren't the only risks. It also increases the risk of prostate enlargement, congestive heart failure, male breast cancer, possibly prostate cancer, and pulmonary embolism or blood clots.

  • 10:18:15

    REHMSo there are lots of issues associated with testosterone, the first being the question of how to determine low testosterone. Short break here and when we come back, we'll take your calls, your email. Stay with us.

  • 10:20:00

    REHMAnd welcome back as we talk about benefits and risks of testosterone use which prescription testosterone has gone up dramatically in the last ten years or so between 2001 and 2011. Hormone use by men over 40 nearly quadrupled. Here's an email. "My husband," she says, "of 20 years was removed from a restaurant after jumping up, drawing back his fist and shouting that he was going to hit me. He had been taking testosterone for a few months and had just had his dose increased. He had never done anything like this before."

  • 10:20:58

    REHMShe goes on to say, "I believe this therapy is dangerous. Our doctor admitted it can cause aggression, as did the domestic abuse hotline I called. What does the research say?" Dr. Fisch, can you talk about that?

  • 10:21:19

    FISCHWell, let's be honest, Diane. That's one case. I mean, I've treated thousands of men with this, and I have never seen that. The issue is -- that we brought up before -- how do you diagnose the low testosterone hypogonadism? And should men be treated who have normal testosterone levels? That's really the bottom line, because you don't know if that man that you were just describing was over treated, and it's very important.

  • 10:21:42

    FISCHAnd what Dr. Fugh-Berman said was absolutely correct. You know, there is no defining testosterone level by which we can say that somebody is hypogonadal. And there is no symptom per say that we could say, ah, that person has low testosterone. Hypogonadism is a clinical situation that requires both a low testosterone level and clinically relevant symptoms together, not one or the other.

  • 10:22:05

    FISCHSo people should not be screened for just testosterone levels because the truth is, it brings up issues that they're not aware of and they may be over treated in those patients. And what I mean by that is, in the article in the Plus One study that we're talking about today where there's an increase incidence of heart attacks and strokes, the bottom line of that study was that during that study they didn't even know which men -- or what the testosterone levels were in the men that were treated at the VA hospital.

  • 10:22:34

    FISCHAnd we know that men are being treated who have normal testosterone levels. Studies have come out that showed well over one-third of men who are receiving therapy -- testosterone therapy have normal testosterone levels. So back to your statement, if you're going to take a person who has normal testosterone levels and you're going to increase their testosterone levels above normal, well, you know, those have risks associated such as heart attack, stroke, aggression.

  • 10:22:59

    FISCHBut if we're trying as doctors -- and I -- as I said, I treat thousands of men. This is my specialty -- we want to maintain the testosterone levels in the normal range only. And when we do that...

  • 10:23:09

    REHMAll right. Dr. Fisch, I want to be clear about one thing. Are you paid by the company that produces AndroGel?

  • 10:23:21

    FISCHI am not paid by any company at this point. In the past, I was paid by AbbVie to actually bring product awareness -- disease awareness, I should say. But I've never ever talked about a specific drug per se.

  • 10:23:34

    REHMAre you on the website that is associated with...

  • 10:23:37

    FISCHYes, I am.

  • 10:23:40

    REHM...AndroGel or any of the other drugs?

  • 10:23:43

    FISCHI am on the AbbVie -- or it's called AbbVie website and is at lowT.com website where I discuss the disease itself, but not which drugs to take. And as I said...

  • 10:23:53

    REHMAll right. All right. And to you, Dr. Fugh-Berman.

  • 10:24:00

    FUGH-BERMANWell, we don't really know what normal testosterone levels are.

  • 10:24:04

    REHMHow is that? How come?

  • 10:24:06

    FUGH-BERMANWell, for one thing, well they vary widely in individual men but they also vary by the hour. They vary by the day. They're generally highest in the morning. They can actually increase with job status. They can increase with exercise. They can increase with whether your sports team won or lost that day. So there are many factors that increase or decrease testosterone levels. Caretaking apparently decreases testosterone levels.

  • 10:24:34

    FUGH-BERMANBut, you know, to return to your reader's comment, testosterone can increase aggression, and not just in people but also in pets. Since these gels are sometimes rubbed on the chest or other places where someone might come into contact with a child or a pet, this is actually caused...

  • 10:24:54

    REHMWell, that's a warning, isn't it?

  • 10:24:56

    FUGH-BERMANYeah, it...

  • 10:24:56

    REHMI mean, isn't there a warning on the ad that says, make sure that you as a woman, if you're pregnant, you do not touch that site?

  • 10:25:09

    FUGH-BERMANRight. Or -- and children as well. If a man is hugging his child, there might be gel that gets on the child. And even pets who've been handled by men who've been using testosterone sometimes become more aggressive.

  • 10:25:24

    REHMNow here's another email from James in Orange, Va. who's 60 years old. He says, "I watched one of those ads last night on TV. The side effects were laughable, swelling, bleeding, headaches. Don't let women and children touch that spot where testosterone was applied. I cannot," says James, "imagine that, given proper notification of the potential side effects, any sane person would choose to take this drug. What could be the benefits?" Roni, let me ask you that. Did researchers find benefits?

  • 10:26:16

    RABINThere's actually a big NIH trial going on right now at University of Pennsylvania to look at the benefits. And that's one of the questions in IOM report, an Institute of Medicine report about a decade ago said was still actually a question, what are the benefits? But, Dr. Fisch, do you want to add to that?

  • 10:26:35

    FISCHOh, I'd love to add to that. You know, my patients who have low testosterone, primary testicular failure that cannot make testosterone, this is a life-saving medication for them. And, I mean, that because literally these people who have no -- are unable to make their own testosterone benefit dramatically: their increased energy level, muscle mass, less of a chance to get diabetes, more exercise tolerance.

  • 10:27:02

    FISCHAnd, you know, I've been -- my patients have been written up in magazines about this. So while you're presenting patients that have dramatic side effects, I could present tons of patients, and I mean tons -- tons was by weight -- maybe thousands of patients that actually have benefitted by the testosterone levels.

  • 10:27:16

    REHMAll right. Dr. Fugh...

  • 10:27:17

    FUGH-BERMANBut, Dr. Fisch, you also mentioned that people who don't have low testosterone who are given exogenous testosterone as a drug, what happens to them?

  • 10:27:26

    FISCHWell, first of all, I consider that malpractice. If some doctor is treating patients who have normal testosterone levels and not -- or not even checking their testosterone levels, well that is not the approach that I take. It's not the approach that the Endocrine Society recommends or anybody recommends...

  • 10:27:42

    REHMAll right. Dr. Fugh-Berman.

  • 10:27:43

    FISCH...because that's just treating them and getting complications.

  • 10:27:46

    FUGH-BERMANYeah, a couple of things that need to be said. One is that testosterone may improve mood, which of course will make people feel better about a lot of things. And there's a very strong placebo effect. Things like libido and fatigue and mood are very amenable to the placebo effect. And this is a very dangerous placebo. But the other thing about health benefits, I'd really disagree with you there, Harry. In fact, we know from studies of eunuchs who have had their testicles removed that they actually live longer than people with normal testicles.

  • 10:28:25

    FISCHWell, I don't treat eunuchs but I can tell you that patients that I see that develop testicular failure are in a terrible situation in terms of depression, low muscle mass. As I said, a lot of them are overweight. I've had tremendous success in men. We talk about, you know, mood, sex drive and everything.

  • 10:28:41

    FISCHBut it turns out that, in order to lose weight, I see tremendous weight loss and consistent weight loss in men who have normal testosterone levels. And in the general medical community, we know that anybody can lose weight, but it's maintaining the weight loss over time. We don't want those yo-yo diets. We want to build muscle mass and maintain people's ability to maintain that weight loss. And I've had -- I treat patients like this. And I've had tremendous success with it.

  • 10:29:04

    REHMAll right. Are there any -- are there side effects, Dr. Fisch, that you can talk about?

  • 10:29:11

    FISCHYes. Yes. There's very important side effects, and some of the studies including the Plus One study and the past studies are very important to discuss. Every testosterone therapy is not the same. Everyone is different. For example, the gels are different than injections. And in this study that just came out, we don't know how many men were on injection therapy as opposed to just gel therapy. Now why is that important?

  • 10:29:35

    FUGH-BERMANThe most common treatment was gel in the (unintelligible)...

  • 10:29:38

    FISCHI didn't see that in the -- yeah, but I...

  • 10:29:40

    FUGH-BERMANIt states in the paper.

  • 10:29:42

    FISCH...but you don't know how many men had injections. And the injections are the ones that are at the highest risk of having heart attacks and strokes. For example, when we give an injection, we get a super normal testosterone bump. And those are the men that I worry about in my practice. And I constantly get red blood cell counts, hematocrits, because that's where you see an increase in red cell count and a higher chance of having heart attacks and strokes. I'm very worried about those people.

  • 10:30:05

    REHMAll right. I want to open the phones now, 800-433-8850. Let's go first to Dan in Asheville, N.C. Hi, you're on the air.

  • 10:30:22

    DANHi, Diane.

  • 10:30:23

    REHMHi there.

  • 10:30:25

    DANI have a brother who has -- OK, he's 35 years old, and he's been taking testosterone for the past two years. And it just seems like -- I'd like the panelists to discuss maybe the personality changes that a person goes through. Because he just keeps -- he's having problems with his family. He's having problems with his coworkers.

  • 10:30:49

    DAN CALLER)And it just seems like the doctor who's prescribing it, the testosterone, just keeps upping and upping his dosage as he goes along. He started off with the cream, and now he's gone to shots. And it just seems like all the problems that he's has in the past two years with taking the testosterone has correlated it with when he started.

  • 10:31:11

    REHMDan, do you have any idea why he went to the doctor in the first place? Why this was prescribed at all?

  • 10:31:23

    DANFrom what I understand, Diane, he was just like your panelists were discussing before. He was just chronically fatigued. He was, you know, he was just kind of "depressed" a little bit.

  • 10:31:34

    REHMThat's interesting. All right. Dr. Fugh-Berman.

  • 10:31:37

    FUGH-BERMANTestosterone is not an appropriate treatment for depression or fatigues. We have better, safer treatments for that. And there's actually no evidence that testosterone actually helps either of these things. So that's a really concerning story. It'd be great if you could convince him to go off and maybe change doctors.

  • 10:31:56

    REHMWhat would...

  • 10:31:56

    DANI mean, the thing is, when we try to talk to him about it, he's almost as if he's become addicted to the testosterone. He doesn't want to talk about it. He doesn't -- he thinks the testosterone has helped him. And, you know, it feels like he's on steroids almost.

  • 10:32:13

    FUGH-BERMANHe -- well, he is on steroids. Testosterone is a steroid. And it would be maybe -- maybe pointing out some of the risks like a heart attack might be useful for him. But that's a very concerning story. And unfortunately there is all of this promotion that is going on in medicine, the physicians as well, to convince them that it's OK to give testosterone to men who don't need it. And there may be other undiagnosed medical problems like depression that really -- they're important. They need to be treated, but they do not need to be treated with testosterone.

  • 10:32:50

    REHMRoni, can you tell us about the studies of the older men and the kinds of symptoms they presented with?

  • 10:33:04

    RABINWell, there was a randomized control study quite a while back that was stopped by safety monitors. It was a small study. It was one of those with a control group that received a placebo. They -- and these were older frail men, frail elderly men. And they were giving them testosterone. And so that they -- the ones receiving the testosterone really did gain strength in their chests and their legs. They were able to walk upstairs faster. They were able to carry things. But they did start having heart attacks at high rates.

  • 10:33:34

    REHMWow.

  • 10:33:35

    RABINAnd the safety monitor saw this and put an end to the trial. That was quite some time ago. There were questions about how old and frail these men were, and whether the doses they received were correct. But that was done probably, you know, quite -- several years ago.

  • 10:33:54

    REHMAll right. And you're listening to "The Diane Rehm Show." Let's go to Gary in Arlington, Va. You're on the air.

  • 10:34:05

    GARYYes. Thanks so much for taking my call.

  • 10:34:07

    REHMSure.

  • 10:34:08

    GARYI am 63 years old and I've been on testosterone gels for four years. When I was 59 I was just feeling old and cranky and there was no joy in life. And I mentioned this to my doctor, you know, during my routine physical. And he took, you know, of course, the blood work, and, sure enough, I was very, very low in my testosterone count. And, you know, I just feel like a new person within two or three weeks of starting it.

  • 10:34:40

    REHMMm hmm. Now what about that Dr. Fugh-Berman? Can a doctor simply measure that testosterone level through the blood and assume that that's the problem?

  • 10:34:57

    FUGH-BERMANNot really. Not only do the levels vary by what lab you send it to, but it also varies by the hour and varies by the day. And we don't really know what a normal range is.

  • 10:35:09

    REHMOK. But Gary is 63. He says he's felling lots better. Dr. Fisch, I would assume that you would attribute that to the testosterone.

  • 10:35:24

    FISCHOf course. A lot of my patients are like that. And again, I treat these patients. And what I want to make a point about what Dr. Fugh-Berman said, if we have consistently abnormally low testosterone based on what the FDA has allowed under 300 anagrams per deciliter, now that is not the best level for sure, but it is what we have for now. In association with symptoms, treatment of those patients reveal what Gary just said, and that is tremendous increase in strength and libido sometimes and ability to lose weight.

  • 10:35:56

    FISCHBut the thing that I find most fascinating is cognitive function changes. I've had people that tell me -- geez I had one patient said to me, you know, when he came after I started treatment he said, you know Dr. Fisch, now I can read again. I said, what? I didn't even know -- what do you mean now you can read again? He said, I didn't have the concentration ability to read again. So now he's able to read. He's able to concentrate.

  • 10:36:15

    FISCHAnd when it comes to depression, let me make a point that the symptoms of depression and low testosterone overlap. They're very, very similar. And we now know that men who are depressed tend to have low testosterone levels. So the future...

  • 10:36:26

    REHMRoni, I wonder if you found that in any of the studies that you went back to look at.

  • 10:36:36

    RABINWell, I'm -- there are a couple things I just want to say. First of all, the caller -- it was a little bit déjà vu. You know, in medicine you're always trying to balance the benefits and the risks. And this idea that you take something that makes you feel great, we heard that for years about hormone replacement therapy for women during menopause. For years, we thought that was terrific.

  • 10:36:59

    RABINIt would prevent heart disease in women. It would keep them healthier for longer and keep them vital and having great sex lives and their skin and everything. It was supposed to be the magic pill. It turned out not to be the case. We actually found out once we did randomized controlled trials that there were a lot of risks to that. And I think we need to be careful.

  • 10:37:18

    REHMAll right. We've got to take a short break here. Roni Caryn Rabin is a medical reporter for the New York Times. When we come back, more of your questions, comments. Stay with us.

  • 10:39:58

    REHMAnd in this hour we're talking about testosterone, the prescribed medication given to men, and indeed some women are using it. We invited the makers of several of the top-selling testosterone drugs to be on the program. Most were not able to get back to us before the program began. But Eli Lilly, maker of Axiron, sent a statement. It reads in part, "Axiron is a prescription medication approved by the FDA for men with certain conditions associated with a deficiency or absence of testosterone.

  • 10:40:49

    REHM"Lilly does not condone the use of our medication for off-label purposes. Patient safety is Lilly's top priority. They actively monitor all adverse events, including cardiovascular events reported in clinical studies and clinical use. Lilly continues to review available safety information, including cardiovascular safety information to determine if updates to the Axiron label are needed." Dr. Fugh-Berman, would you be in favor of a big or larger warning label on drugs containing testosterone?

  • 10:41:45

    FUGH-BERMANWell, there's certainly does need to be a change in the warning label. And in fact, the FDA has announced that it is going to look into these adverse events that have been really cropping up in a lot of studies lately. And by the way, the FDA does not make a mention of what testosterone level in the blood should be treated.

  • 10:42:05

    REHMSo give me a range in numerical terms of what one might see as a range of testosterone levels.

  • 10:42:19

    FUGH-BERMANSo it could be anywhere from zero in somebody who doesn't have testicles, up to over 1000. And various people have said low testosterone is under 150 or 200 or 250 or 300. It's not well established what low testosterone is.

  • 10:42:37

    REHMDr. Fisch, how do you determine what low testosterone is?

  • 10:42:44

    FISCHI follow the Endocrine Society guidelines.

  • 10:42:46

    REHMWhat are those?

  • 10:42:47

    FISCHAnd those are the guidelines that say if a testosterone is below 300, with symptoms -- I want to make an important point. It is not the level that's important. It's the level and the clinical symptoms combined. We are not sure…

  • 10:43:01

    REHMBut the clinical symptoms, Dr. Fisch…

  • 10:43:04

    FISCHYes.

  • 10:43:04

    REHM…I gather you would agree, are fairly vague.

  • 10:43:09

    FISCHThey are vague, but the number one, number two symptoms are fatigue and low libido. And those are things that we see marked increases in with the treatment -- with people who have low testosterone. That's what I see in my clinical practice. So the bottom line is there are guidelines by the Endocrine Society. And in terms of warning labels, yes, the FDA -- you always have to take a look at what happens in the clinical situation, what happens in the population. But important to remember, promotion to men who do not have low testosterone is wrong.

  • 10:43:40

    REHMAll right.

  • 10:43:40

    FISCHIt is only for men that have low testosterone and symptom for a condition called hypogonadism.

  • 10:43:45

    REHMOK. But…

  • 10:43:47

    RABINI think…

  • 10:43:48

    REHMGo ahead, Roni.

  • 10:43:49

    RABINI'm just wondering, though. Men's testosterone levels do seem to decline with age in a normal age-related decline. And the question is how do these guidelines fit into that? And should they be adjusted if this is a normal age-related decline?

  • 10:44:04

    REHMDr. Fugh-Berman?

  • 10:44:06

    FUGH-BERMANRight. And that's really unclear what are "normal" levels for different ages. So that's really an important question, but also the Endocrine Society takes quite a lot of money from drug companies. And you actually get different answers when you look at who's getting paid.

  • 10:44:27

    FUGH-BERMANSo, for example, there was a meta-analysis of adverse events in testosterone trials and when they divided out the trials into which ones had been funded by pharmaceutical companies that made testosterone and which ones had not, they found that the industry-funded trials found no increased cardiovascular risks, but that the non-industry-funded trials did find an increase in cardiovascular risk. So it's always important to follow the money.

  • 10:44:52

    REHMDid you see that -- hold on, Dr. Fisch. Did you see that, too, Roni, in terms of the kinds of studies being done?

  • 10:45:06

    RABINWell, the meta-analysis that Adriane talked about, definitely was able to separate it out and saw that the trials that were funded by industry did not see as big an increase as the ones that were independent. And I think we do see this fairly consistently. Even in talking to -- when I do my interviews, I'm always very careful to ask if people have industry ties. And the tone changes dramatically, and it's often consistent with that.

  • 10:45:36

    REHMAll right. I want to take another call. This from Louisville, Texas. Hi, Brett. You're on the air.

  • 10:45:44

    BRETTHi, Diane. My question is -- if you guys could talk about how doctors are actually compensated. My sister-in-law is actually a drug rep. And she says that oftentimes doctors get direct payments for prescribing certain drugs. And they also may get Super Bowl tickets or sports tickets. And if you guys could talk about how that may be influencing some doctors to make some of those decisions, I would appreciate it.

  • 10:46:07

    REHMAll right. Roni, I wonder if you've seen any of that.

  • 10:46:13

    RABINWell, I don't know about direct payments. I wouldn't know how that would happen. There's definitely been a big gift and dinner and lunch industry. And there have been efforts to crack down on that and have more transparent reporting. I think actually one of the most dangerous things is that so much information is coming directly from drug companies to physicians, and there isn't always moderation of that. So there's a lot of education that drug companies are doing of physicians.

  • 10:46:45

    REHMAll right.

  • 10:46:45

    RABINAnd that education may not be as complete or comprehensive or somewhat biased.

  • 10:46:49

    REHMDr. Fisch, do you want to comment on the question?

  • 10:46:53

    FISCHOf course, I'd like to comment on the question, Diane. It turns out that giving money or Super Bowl tickets to doctors is illegal. You can't do that. In fact, they don't even give pens out anymore. What they do do is they do sponsor doctors to educate other doctors. And that's where they have the dinner programs and things like that. And I'm all in favor of that. But I could tell you that I know for a fact it is illegal to really compensate doctors for writing prescriptions.

  • 10:47:19

    REHMDr. Fugh-Berman?

  • 10:47:21

    FUGH-BERMANIt's illegal to pay someone to write prescriptions, but it's not illegal to give gifts at all. And there's many ways in which pharmaceutical companies affect physicians. So not only do drug reps target physicians who control market share or might be writing a lot of branded prescriptions, but also pay physicians to be speakers, they pay them to be consultants, they pay to essentially do fake clinical trials where they're being paid to enroll patients in clinical trials that don't really exist. So there's different ways of paying somebody without it being a direct payment for a prescription.

  • 10:48:02

    REHMRoni, I'm wondering to what extent the studies looked at the number of advertisements on television, correlating them with the increase in use of these prescription drugs.

  • 10:48:23

    RABINI am not aware of studies that looked at that correlation. Dr. Fugh-Berman may know more about that. There certainly has been an enormous amount of money poured into advertising, about $100 million has been spent on advertising specific brands of drugs. And then there's additional money that's spent on raising awareness of the condition and the disease that's not even tracked the same way. And there's a correlation between that increase and the increase in sales and increase in prescriptions.

  • 10:48:57

    FUGH-BERMANYes, absolutely. And, of course, drug companies don't spend money on things that don't work. And direct-to-consumer advertising is important. Those ads are very creative. But in the industry they actually have -- industry says that it's more important to get to the doctors because they're the ones who really have the prescription pad.

  • 10:49:16

    FUGH-BERMANAnd certainly it increases the acceptability of therapies to have direct-to-consumer advertising. But as Roni mentioned, medical education or continuing medical education -- a lot of that is funded by pharmaceutical companies. And it always has subtle messages in it that do not necessarily even mention brand names.

  • 10:49:38

    FUGH-BERMANIt's all about what Dr. Fisch called disease awareness, convincing physicians that a particular disease state, as industry calls it, is underdiagnosed, it's affecting a lot more people than we think, that it's having a dramatic effect on people's lives. That's the job of these physicians who are key opinion leaders. It's their job to tell other physicians that a particular disease is underdiagnosed and needs to be treated more often. Low T is a perfect example of that.

  • 10:50:08

    REHMDr. Fisch, do you want to comment?

  • 10:50:10

    FISCHOf course. Hypogandism is a disease. It's something that has been underdiagnosed in the past.

  • 10:50:16

    REHMBut how rare is that, Dr. Fisch?

  • 10:50:20

    FISCHWell, it's not rare in my practice since that's all I do as a fertility doctor. I could tell you that many people who have hypogonadism have low sperm counts and are infertile. Men who have hypogonadism tend to have low libido, sexual dysfunction problems, in addition to a myriad of other problems associated with it. It is real. I'm the only person on this panel that actually treats patients.

  • 10:50:40

    FISCHAnd as a professor at an Ivy League university, I'm telling you that this is an actual disease and not to make fun of a disease because you're not aware of all of the symptoms or all the problems associated with it. I want to make a point about the studies that say there is a problem. In the Plus One study, I want to make a point that patients treated at the VA center did not have testosterone levels.

  • 10:51:01

    FISCHWe don't know if they were men who had normal testosterone levels or below testosterone levels. And only men who were hypogonadal with low testosterone levels should be treated. There are risks associated with these medications for people who should not be treated, who have normal levels and whose levels go into super normal, extra, above normal levels, and that's where you see the problems.

  • 10:51:21

    REHMAll right.

  • 10:51:22

    FISCHSo a doctor has to be educated and has to know how to treat patients. And patients need to be aware of all the risks and benefits associated with these medications.

  • 10:51:27

    REHMAll right. Let me take another call. Dana, in Ft. Worth, Texas, you're on the air.

  • 10:51:34

    DANAHi. Good morning.

  • 10:51:36

    REHMHi.

  • 10:51:38

    DANAMy sister is 46 and perimenopausal. And she went to a homeopathic doctor, if you will, and was prescribed testosterone injections that she does twice a month. And I'm wondering if any of these studies or side effects are relevant to women?

  • 10:51:57

    REHMDr. Fugh-Berman?

  • 10:51:58

    FUGH-BERMANWell, there are these anti-aging clinics that unfortunately will mix together different hormones often in compounded preparations. They might mix estrogen and testosterone and other kinds of things together. So, yeah, this is both in conventional medicine and also in alternative medicine. But there's no such thing as a harmless hormone. Hormones affect the whole body. We know about the problems with menopausal hormone therapy. We're going to see an epidemic of adverse effects from testosterone.

  • 10:52:30

    FUGH-BERMANIn women, the FDA has actually turned down several -- well, they turned down testosterone treatment for libido in women because it didn't work very well and they were concerned about safety. Women with higher testosterone levels, naturally-occurring testosterone levels, for example, have higher breast cancer rates. And there was just a testosterone gel study in women that was stopped also for lack of efficacy.

  • 10:52:55

    REHMAnd you're listening to "The Diane Rehm Show." Let's go to Jim in Tallahassee, Fla. You're on the air.

  • 10:53:06

    JIMHi, Diane.

  • 10:53:07

    REHMHi.

  • 10:53:08

    JIMYou deserve a medal. I recall a parallel discussion on your show about women and calcium levels. And it seems as if the pharmaceutical companies were creating these classes of patients who were not quite ill or diseased, but feel that they need to be treated. My calcium's low. I should be taking some sort of supplement. And I'm wondering that this low T thing doesn't strike very similar chords of trying to get people who may not have disease wanting to treat their fatigue or their, you know…

  • 10:53:54

    REHMAll right. Thanks for your call. Dr. Fugh-Berman?

  • 10:53:57

    FUGH-BERMANSure. It's a really great point because there is a lot more well people than there are sick people. So well people are a much larger market. And if pharmaceutical companies can convince people who are perfectly healthy that they need a drug, they can sell a lot more of that drug.

  • 10:54:14

    REHMAll right. To David, in Lillian, Ala. You're on the air.

  • 10:54:21

    DAVIDGood morning.

  • 10:54:21

    REHMHi.

  • 10:54:22

    DAVIDI've been through the ringer on this. I'm 60 years old in two days, and in 1995, exactly to the day of my birthday, I went for an operation. I tore a solar plex muscle in the Marine Corps, and I put up with it since '74 until '95. The guy did the surgery. It went horribly wrong. They left a twist tie on the vas deferens. The gonad swelled up to giant, and it stayed like that for 20 months. Hard as stone and months later, I went and saw a urologist. She put me on testosterone.

  • 10:54:53

    DAVIDShe said, there's nothing we can do now. They should have opened you up and took the twist tie off of there. She goes, why was it on there in the first place? I didn't know. I've got a picture of it. And there was nothing I could do about it. But I've been taking the testosterone cypionate, and I got down to a half cc every 10 days.

  • 10:55:09

    DAVIDAnd I've been doing this for all these years. I can't find out what exactly it's made out of. Synthetics, they told me -- was best I could come up with for an answer. Does it cause tumors on organs? I've heard of heart disease three times greater. I was a distance runner. I've gone up and down with the mood swings and all the weight.

  • 10:55:27

    REHMAll right. David, it sounds as though you've got multiple problems going on. And I do hope you'll continue to check in with your own doctor. What would you say to him, Dr. Fisch?

  • 10:55:45

    FISCHWell, it sounds like David had a testicular problem and probably had low testosterone -- although I am not his doctor. But if you're losing a testicle, remember, that's the organ that makes testosterone. So you very likely had hypogonadism. And the medication for him may have helped some of his symptoms. But of course once you're on this medication you need to have follow-up with, again, testosterone levels and red blood cell counts and estrogen levels to see if they're increased in any way because those -- if it's increased you need other treatment to avoid those increases.

  • 10:56:16

    REHMAll right.

  • 10:56:16

    FISCHAnd, as said, the injections are the ones that cause more problems than if it's in the normal range.

  • 10:56:20

    REHMAll right. And finally, Dr. Fugh-Berman, do you believe that this is a drug looking for a disease?

  • 10:56:34

    FUGH-BERMANYes, absolutely. It used to be before we had these gels that were injections. And there certainly were companies trying to sell the concept of male menopause or andropause to men, but it's hard to get them to take injections. So since they've been available in gels it's really increased the market and increased the opportunities for creating a disease state in men.

  • 10:56:55

    REHMSo you believe there have got to be lots more studies?

  • 10:57:01

    FUGH-BERMANNo. I actually think we have enough studies to say healthy men shouldn't use this.

  • 10:57:04

    REHMAll right.

  • 10:57:04

    FISCHThat's true.

  • 10:57:06

    REHMDr. Adriane Fugh-Berman of Georgetown University, Dr. Harry Fisch -- he's professor of urology and reproductive medicine at New York Hospital and Cornell University -- and Roni Caryn Rabin, medical reporter in the New York Times, thank you all so much.

  • 10:57:30

    FUGH-BERMANThank you.

  • 10:57:31

    FISCHThank you.

  • 10:57:31

    RABINThank you.

  • 10:57:31

    REHMAnd thanks for listening. I'm Diane Rehm.

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