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Professor Schulman: Now we follow on some other body function. That’s Professor Köhn from the University of Munich, who will address several of these aspects.
Professor Kohn: The problem of an older-growing population is a worldwide phenomenon as we see here, which cannot only be observed in so-called industrialized countries; we have it also in so-called developing countries and WHO has estimated that, in just about 15 years, approximately 700 million people older than 60 years will live in so-called developing countries and just about one billion people over 60 years old will live worldwide.
The life expectancy of a man who is 80 years old today is 7 to 8 years now. For these men, quality of life is also dependent on the ability to be active and to participate actively in physical activities. For the health systems, it is important to save costs which may be associated with loss of physical activity and with age-related illness.
One example is the increase of bone fractures here, for example, in the male population with increasing age. Therefore, the WHO Aging and Health Program has focused special attention on the maintenance of physical activities in the older-growing population. For the health systems, it is important, as I mentioned before, that they keep their physical activity.
One clinically relevant aspect to maintain physical activity is the association between testosterone and body composition and functions. We have seen this picture before in another way and, of course, we have heard that one of the important target organs of testosterone is the brain but, in terms of body composition, we have to focus our attention, for example, on muscle mass, fat mass and even skin and of course, bone.
This picture summarises a different aspect of body composition of an elderly hypogonadal man with decrease of the muscle mass, increased fat mass, loss of secondary hair and gynaecomastia.
Men with low testosterone report about a decrease in strength and endurance and the ability to play sports. This graph here is from a study we have done in different centres all over Germany and in other European countries. These were men older than 50 years who had been screened for a multi-centre study to evaluate the effect of testosterone undecanoate in aging males. Just about 90% of the men with low testosterone reported about decreased ability to play sports
and the same was true, for example, here, for their strength and endurance. Again, just about 90% to 100% of the men we had screened reported about their deterioration in strength and endurance and we see lower percentages of the aging males reporting about the decrease in strength within total testosterone serum levels of above 5 ng/ml.
Of course, we see that, and we have heard about these studies before, testosterone has a positive effect on bone mineral density. It can improve body composition and some of the problems older men are complaining of. It can increase the bone mineral density and this is important, this is only a representative study for all the studies we have heard about before, that there is in fact no difference in the effects of testosterone treatment between younger and older age groups.
At the same time, the total body mass is decreased, the lean body mass is increased and, in this study and I will come back to this later, the leg strength shows an increase, but this is still up for discussion because not all studies have really shown that muscle strength can be induced or can be increased by testosterone treatment.
The effects on bone mineral density are not only due to quantitative changes but are also associated with qualitative changes, such as the trabecular architecture such as we have seen here. This is a very small study with hypogonadal men, but we see with this micro magnetic resonance microimaging that the trabecular architecture can be changed by testosterone treatment.
Several studies have also demonstrated that improvement of bone mineral density can be achieved with different application forms of testosterone. Here, for example, with the Testim® gel and you see the same trend with an increase of bone mineral density after 12 months of treatment in hypogonadal men.
We see the same effect, for example, here in the decrease of fat mass, the increase of body mass, these numbers here are within the range which has been reported in other studies, as well, and you see here the treatment for 12 months.
Again, if you compare the different treatment application forms of testosterone with a gel or with a transdermal application form with a patch, you see that both applications in terms of lean body mass and percentage of fat mass are comparable and even a little bit higher if you take the 100 mg application form.
The impact of testosterone on muscle mass is mediated by different changes of cell physiology. We have a stimulation of mitosis and myoblasts, a stimulation of ribosomal activity, stimulation of RNA polymerase synthesis and the increase of production of contractile and non-contractile muscle proteins.
But, again, as I have mentioned before, there is still a matter of discussion if muscle strength is really increased after treatment with testosterone. We have seen the study by Wang before. This is a study by Snyder who could not show that testosterone treatment of hypogonadal men caused an increase of muscle strength but, again, we saw a reduction of fat mass and an increase of body mass.
Since the improvement of body composition requires a multifactorial approach, associations between testosterone and diabetes mellitus are of clinical relevance. It is known that the frequency of hypogonadism in diabetic men is significantly higher than in the non-diabetic control groups.
Testosterone is positively correlated with the insulin sensitivity and we see a three-fold increase prevalence of metabolic syndrome in men with hypogonadism and a body mass index higher than 25. There are only a few studies, but there are more studies going on at the moment, dealing with the problem of treatment of diabetic men with testosterone if they are or when they are in a hypogonadal status.
We see here that the metabolic conditions of men with hypogonadism and diabetes can be increased by treatment with testosterone.
At the same time, the body mass index and the fat mass can be changed in these men. Here we see the decrease in the body mass index in hypogonadal men with diabetes mellitus after treatment with testosterone and the same was true here for the decrease in fat mass in these patients in the same way and this was after only three months of treatment.
Let me focus your attention to the skin at the end of my talk. This picture shows an elderly man with a tremendous gynaecomastia, a pruritic eczema and hypogonadism. By the way, this gynaecomastia was also attributed to the intake of spironolactone.
We know what age-related changes can be observed in the skin and some studies have already focused on the effects of testosterone substitution therapy on skin physiology during testosterone therapy. It could, for example, be shown that epidermal thickness is increased after therapy of hypogonadal with testosterone. However, we need more information about other effects of testosterone on the skin, such as immunological capacity, for example. The first reports about improvement of eczema in hypogonadal men after testosterone therapy and we did a study, for example, in endocrinological patients attending the endocrinological outpatient department to examine the association between so-called atopic (inaudible) and hypogonadism and we saw an increase of testosterone and an increase in atopic diseases like hay fever, atopic eczema, asthma, allergic asthma and hypogonadism. So we need to really focus on many other aspects of body composition.
In addition, some of the important clinical aspects of testosterone substitution therapy have to be clarified. Is the risk of fractures after therapy of hypogonadal men with testosterone really decreased and is the cardiovascular mortality of hypogonadal men after treatment with testosterone really decreased?
Let me conclude the messages of this talk. Testosterone treatment of hypogonadal men has positive effects on body functions and composition. These effects can be demonstrated in young and older hypogonadal men. There does not seem to be a difference. Results of different testosterone therapies are comparable. Transdermal systems with gels, with patches, intramuscular substitution of testosterone esters and testosterone treatment of hypogonadal men suffering from chronic diseases like for example, diabetes mellitus, but also renal failure, organ transplant receivers, can improve their general health.
Thank you very much.
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