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Steve: This is Steve Freed with Diabetes in Control and we are here in San Diego with American Diabetes Association 77 scientific sessions. We have some great interviews with some of the top endocrinologists all across the globe. Today we have with us a special guest, Dr. Ronald Swerdloff. Why don’t we start off by you telling us a little about yourself?
Dr. Swerdloff: My name is Ronald Swerdloff and I am a professor of medicine at the David Geffen School of Medicine at UCLA, the chief of division of endocrinology and metabolism at the Harbor UCLA Medical Center, and the senior investigator at the LA Biomedical Research Institute.
Steve: That’s great! I know you are here presenting, making you can tell us the title of your presentation!
Dr. Swerdloff: I am going to talk today about relationship between male hypogonadism, which is low testosterone, and diabetes mellitus.
Steve: Can you tell us about male hypogonadism?
Dr. Swerdloff: Male hypogonadism occurs in men when they have a decreased production and secretion of testosterone from the testes. Sometimes, it is referred to as the low Tsyndrome. With that they have certain symptoms as well as having low testosterone levels.
Steve: Does that have a lot to do with sexual dysfunction?
Dr. Swerdloff: Yes, individuals who have low testosterone levels may have decreased libido – decreased sexual function. They also have increase in osteoporosis, decrease in mood in many instances, and they have decrease in muscle mass and increase in obesity. So all these manifestations are important clinically.
Steve: Can adding testosterone replacement increase the risk of cancer, because I know personally that testosterone is the fuel for prostate cancer.
Dr. Swerdloff: This is an interesting issue that goes back to Dr. Huggins winning the Nobel Prize for showing that testosterone with metastatic prostate cancer resulted in worse symptoms, however, most of the evidence at the present time has failed to show the direct relationship between the testosterone levels and the development of prostate cancer. Furthermore, it has failed to show that testosterone will make subclinical prostate cancer worse. Nevertheless, there are warnings that say that in people with prostate cancer you should you either not treat, or be careful in management of those patients if you treat them with testosterone.
Steve: What are some of the things that can be used to lower the testosterone levels?
Dr. Swerdloff: There is a number of things that have been used to lower testosterone. There are substances which act on the pituitary gland and lower parts of the brain that turn off the productions of the signals to the testes. Those became very popular in treatment of patients with advanced prostate cancer. However, it resulted in a large number of complications and the patients haven’t done very well. So, its beginning to fall out of favor.
Steve: When you have low testosterone and adding testosterone replacement, does that possibly increase the risk for diabetes?
Dr. Swerdloff: Just the opposite, I think. The issue is that people with diabetes have low testosterone and people with low testosterone have a greater chance of having diabetes. Now, the association is clear, but causality is less so. It is not clear whether or not this worsening of the testosterone-lowering effect in diabetes is not just an effect from chronic illness, because many chronic illnesses lower testosterone levels. We don’t know about specificity of this, but we do know that in diabetes there is a significant percentage of the individuals who have low testosterone.
Steve: When do you add the testosterone replacement for patients with diabetes?
Dr. Swerdloff: This is a very interesting and controversial issue. Because there are people, based upon registry studies, that have been strong advocates for treatment with testosterone to improve blood sugar control. However, meta-analyses have failed to confirm that. So, we need to have more data with double-blinded, placebo-controlled studies to truly know the answer whether or not the treatment with testosterone will enhance blood sugar control.
Steve: Can the male person without diabetes with prostate cancer add testosterone to his treatment without the fear of causing the cancer to become more aggressive?
Dr. Swerdloff: We don’t know the answer to that. There will be long-term safety study that is going to look at the issue whether or not the treatment of patients will low testosterone, not necessarily diabetes, whether or not there will be an increased risk of that treatment on the cardiovascular system and on any types of cancer, like the prostate cancer. That long-term safety study will begin fairly soon, but we won’t know the answer to that for perhaps 5 to 7 years.
Steve: For a person with diabetes and prostate cancer, or for a person with a remission of prostate cancer, is it safe to add testosterone to his treatment?
Dr. Swerdloff: I would say that the recommendation and FDA’s position is that it is not safe to do that. However, some practitioners who are carefully monitoring patients have treated people with testosterone when they have been “cured” from their prostate cancer in order to treat their clinical manifestations of low testosterone. But let’s turn back to the diabetes issue, because that’s really what the conference here is about. We have the following questions: what is the relationship of low testosterone to diabetes? That is very complicated, because people with low testosterone tend to have increased obesity. And people with increased obesity tend to have low testosterone. And obesity and low testosterone add to what we call metabolic syndrome. When you have metabolic syndrome it causes a number of other complications. We have this complex interrelationship. If you lose weight, your testosterone level tends to go up. So, the recommendations are that we should treat people with diabetes and low testosterone first with what we call improvement in lifestyle. That means we are asking those people to lose weight and we ask them to exercise. If they fail to improve the testosterone levels, we recommend that they be treated with testosterone. Not specifically to treat the diabetes, but to treat the symptoms of low testosterone, or what we call hypogonadism. Maybe in the future we will be more aggressive. We may say in the future – if the data supports that – that we will treat people with diabetes even if they didn’t have the symptoms of hypogonadism to improve their blood sugar control but we don’t know that comfortably at the present time.
Steve: There are different forms treating with testosterone. There are creams, and even nutritional products…that haven’t gone through FDA approval. What are the different forms of testosterone that can be given to a patient?
Dr. Swerdloff: There is a number of different formulations and means of administering the medication. The most popular at the present time in the US is the transdermal testosterone. Gels, for the most part, are put on the skin, they are absorbed and they have affect on the whole body. There is also injectable that you inject either subcutaneously or into the muscle in order to get adequate blood levels of testosterone. There are oral testosterones, which are experimentally being developed and are available in other countries but not available in US at the present time. And, there are long-term injectable; things that last for a long period of time after injection. Or, even pellets that can be put under the skin. They all work, including the creams. They all increase testosterone and you aim to get testosterone into the normal range. There are some differences in side-effects because of different routes of administration. But for the most part you can think of the different formulations that the patient with advice from the doctor can decide which is the best for them. Some people like gels on the skin, some people like injections, and some people would prefer to have pills if they are available.
Steve: Can we say emphatically that testosterone does not cause cancer, or do we still have a big question mark there?
Dr. Swerdloff: Most of the feeling at the present time is favoring not causing cancer. However, as I said, the medical community and the group of investigators are going to do a long-term safety study to hope to answer that question.
Steve: As far as causing cancer, that is one question. The other question is for a person who already has prostate cancer, let’s say the prostate is removed, and they are trying to reduce the number of testosterone by giving hormones because they feel it could cause the cancer to come back, or if there is a little bit of cancer still left, does testosterone fuel the cancer. Where are we with that?
Dr. Swerdloff: The recommendation is not to treat people who have existing prostate cancer with testosterone. However, as I mentioned earlier that in some instances if the cancer has been removed and the markers of cancer are absent, then some doctors – urologists and andrologists – have been more aggressive and willing to treat those patients with testosterone if there are symptoms of low testosterone is causing them more problems or serious problems.
Steve: So, you do a blood test, and they find out your level of testosterone. There is a big range of what normal is. What is normal? What is considered normal? And as we get older that number obviously changes.
Dr. Swerdloff: The question you’re really asking is what is your target? You start with low level of testosterone, everybody agrees it’s low, it’s been replicated, you see a low level and then you treat. So what do you aim for? What blood level do you aim for? We do not know for certain of that answer. We aim for levels in the reference range, in the population range, we sort of aim for the middle of that. Maybe for the older people we might aim for a little bit lower level. But, we don’t know for certain exactly what levels we would like to retain.
Steve: What are some specific numbers of that area?
Dr. Swerdloff: In the United States we’ve heard of things in nanograms per deciliter. The reference range, the population range, is somewhere about 280 to about 1000. And that is a big range. What that means is that different people respond to the testosterone, to the hormone in the blood, differently in order to keep the level that their system thinks is the ideal level. That’s the concept that we have. You can’t really tell by looking at somebody who has the value of 400 and compare them to a person with a value of 800 – they look more or less the same. That means that there must be a difference in sensitivity at the end organ that responds to the hormone, that it greater or lesser but both of them one way or another get the same net effect when you look at their clinical manifestations. That is sort of the idea that we have at present time.
Steve: So if a person with diabetes, blood sugars elevated, we start to see sexual dysfunction. Would that person be a candidate for testosterone therapy?
Dr. Swerdloff: Yes I think so. I think that we would then say that this person would be treated for their symptoms of low testosterone. And that those symptoms should improve on treatment. There may be a benefit to blood sugar control, but we don’t know for sure. And there may be risks and today one of our speakers is going to talk about the issues of possible risks to cardiovascular disease, and you already talked to me about possible risk to prostate. Those things are still, as I said, under study. We hope that the risks will be small or nonexistent, but of course we always balance. Any time we treat somebody, we try to balance the benefits and the risks and look for the proper proportion of the two.
Steve: Let’s say someone with testosterone level of 450 has sexual dysfunction due to their diabetes, would there be a benefit of treating him with testosterone?
Dr. Swerdloff: I don’t think so. I think if the testosterone level is within the reference range, value of 450 is pretty good value, I don’t think you would treat that person nor do any of the guidelines recommend to treat that person with testosterone. They may have erectile dysfunction, which is common in diabetes, but that may be entirely independent of the testosterone levels, and have to do with diabetes effect on vasculature, or nerve supply of the penis.
Steve: At what level of A1c do we usually see sexual dysfunction, and can it be reversed? If the person has an A1c of 8, 9, 10, or 11 and reduces it closer to normal ranges, have we seen the nerves in the sexual dysfunction dissipate?
Dr. Swerdloff: We wish that were true. Unfortunately, in many instances, once the problem occurs it may be more difficult to reverse. Although like the peripheral neuropathy that people have in diabetes, and some of the other complications, our thesis is that regulation of blood sugar should have a positive metabolic effect and should be beneficial to the patient. It is a lot easier to understand prevention of these problems than it is correction when they are well established. But, we hope that it would be true.
Steve: I just read an article and they were talking about what makes a good presenter. The findings are that the good presenter is someone that presents their material and the audience takes it home and uses that information, and that medical medical community uses it with their patients. There there are people who have 150 beautiful slides, but you walk out of the door, and you can’t remember a darn thing. It’s a waste of everybody’s time. If you had your druthers what points would you like your audience to take away, so that you don’t waste your time or the audience, and that they are going to put it in their practice?
Dr. Swerdloff: So the first thing that I would want people to recognize is that people with diabetes have a high chance of having low testosterone. And that low testosterone is for the most part driven by failure to be able to produce the normal amount of signals from the pituitary gland – it’s called secondary hypogonadism. That if those symptoms are such that they are clinically important to the patient then they should be treated with testosterone if the value of testosterone is repeatedly low and if the patient has the symptoms that you talk about. Then, I would like people to know that we don’t know for certain whether testosterone treatment will improve glycemic control but there is some evidence to suggest that and we need more data in order to resolve the issue.
Steve: Right now, are there any studies going on to resolve that issue?
Dr. Swerdloff: Yes, there are studies going on to resolve the issue, they are what is called long-term safety studies. They don’t specifically at this time deal with whether or not that improves the blood sugar in diabetics. That study has been done, but it has not been done in the placebo-controlled, evidence-based type of fashion that would convince everybody. That study needs to be done, but it’s a little bit difficult to do because these are people that are on a number of medications and you have to be able to sort out the medication effects in addition to the treatment with testosterone. These are really important issues that need to be resolved and they will be resolved as we go forward.
Steve: What are some of the things we can do to increase our testosterone? You mentioned losing weight and exercise, but is there anything else that can help?
Dr. Swerdloff: Obviously being in good health has a big impact. It’s very easy to tell people to be in good health. But, we do know that lifestyle changes will have positive effects on general health, on cardiovascular well-being; it has an effect upon risk of other types of diseases. It certainly has an impact on your chances of having type 2 diabetes. So, lifestyle changes, which are not so easy to do but very very important, will have impact on both type 2 diabetes and on low testosterone levels. That is the first order. If we can do that, and if it were easy we wouldn’t have conferences about all these things. Everybody would be in great shape and we would have a very small number of people who have these problems. But Type 2 diabetes is increasing and also we are getting heavier, we are eating more, exercising less because we sit at our computers all the time, we don’t go out and work in the field like people did several hundred years ago. So, our life is changing and we have to then adapt to ways to try to improve our general well-being. Those will have impacts both on type 2 diabetes and on low testosterone. But, if we can’t do that, then we have to use medications to try to treat these things. And we have to try to balance the benefits of the medications, both testosterone for low testosterone symptoms and other medications for diabetes to try to control the blood sugar in those instances were we haven’t been able to solve the problem otherwise.
Steve: You mentioned exercise. There are different forms of exercise: there is aerobic and anaerobic. I would think that in order to increase your testosterone that you are looking more towards anaerobic type of exercise and building muscle mass. Is that right?
Dr. Swerdloff: Actually, our goal would be to decrease fat mass. With testosterone when you decrease fat mass, you increase muscle mass with it. But, the real goal is to decrease fat mass, particularly the fat that we have in our abdomen – what is called the visceral fat. We think that visceral fat produces substances, which might influence the testosterone level by acting on the lower part of the brain, in the pituitary, but it also has effects on developing that in the liver and it has an effect on the cardiovascular system – it increases the chance of having a heart attack. So, we would like to reduce this fat. We would of course like to improve muscle mass as we get older, in order to improve our strength and decrease frailty. As you get older what you really want to do is to stay independent. You don’t want to be in a nursing home because you are too frail. So, you want to improve your strength and you want to decrease your fat mass so you don’t have these complications of disease that occur in people that are overweight.
Steve: I want to thank you for your time. I found it very interesting. Enjoy the rest of your stay here.
Dr. Swerdloff: Thank you so much.