Sponsored by an educational grant from Schering
Thank you very much for the invitation to share with you some experience concerning a long-acting testosterone preparation which is testosterone undecanoate now known as Nebido®.
To summarize and give you a short glimpse when testosterone should be used, I just repeat the indications for testosterone substitution. So there should be symptoms of hypogonadism and morning testosterone levels at least below 12 nmol/L at two measurements. There are also contraindications for testosterone substitution, not only for prostate carcinoma, but also desired paternity. You know that external testosterone acts as a contraceptive in males and also relative contraindications from testosterone substitution exist, for example, BPH, sleep apnea, polycythemia or criminal sexual behaviour. One should be careful in such a setting.
So you know that there have been formulations for testosterone treatment before. For example, testosterone in enanthate since the 1950s and they worked quite well but you see that there were markets and fluctuations of testosterone levels when patients were injected with TE and people and patients noticed when testosterone levels decreased, especially when they were receiving the medication at three-week intervals. So for a while, they were below the normal range.
So then testosterone undecanoate came to the market.
And we first tried it in a single dose and what you can see here is, in these hypogonadal men, that testosterone levels increased and then they remained stable after 6 to 8 weeks, so we thought maybe it was wise to inject it every 6 weeks.
And that was what first we done and you see that the trough levels are increasing over time and 6 weeks seemed to be too short as injection interval.
So that was prolonged and finally we found out that 12 weeks are appropriate as injection intervals for testosterone undecanoate 1,000 mg.
For treatment and initial treatment of hypogonadal patients, it is now recommended to give a loading dose. That means you give the second injection already after 6 weeks and then you prolong the injection intervals to 12 weeks.
You should check your patients after 30 weeks or shortly before that for their testosterone levels because they behave sometimes differently. If they have testosterone concentrations around 10 to 15 nmol/L, 12 weeks are fine as an injection interval. If you find testosterone levels to be low, you should go to an injection interval of 10, if they are higher than 15 nmol/L, you can prolong the injection interval up to 14 weeks. So that differs.
You should inject the preparation deeply into the muscle gluteus, you should inject slowly, take at least one minute and the patient should be resting, lying down.
There is no specific storage condition. The durability is 36 months, 24 maybe at 30 and 6 at 40 degrees, but that is rarely met.
So we have an 8-year experience with that preparation in our institution.
And there were patient treated with this testosterone undecanoate, it was not then called Nebido®, 22 of them the mean age around 44. Duration of the treatment differing from patient to patient, but one received the treatment since 8.5 years. Fifteen of these men had primary and 7 secondary hypogonadism.
And you see here the injection intervals which range basically from 10 to 14 and what you see is the number of patients we start with 22. Some people change but most of them received the injections, 11 or 13 injections, but there is one going up to 8 years.
And you see that testosterone levels increase in these patients then remains stable.
That holds how true for free testosterone.
PSA always remained within the normal range. You see that 1.6 ng/mL is still low, so there was safety in that regard.
Also concerning prostate volume which increased of course in these men but then remained stable.
Hemoglobin levels and hematocrit are a very important issue when you treat older men, especially older men with testosterone and what you see here, there are changes but they occur during the first year and that is the critical year when you start testosterone therapy and that is when you monitor your patient, after that, everything to be stable.
For body weight and body mass index, there were no real changes.
Bone density increased in these men but since reached a stable condition after 2 to 3 years. Of course, it takes some time for the bone to change.
Total cholesterol and triglycerides decreased.
As well did LDL and HDL cholesterol, but you always have to remember that this is only patient, so this is an observational study. This is long-term experience. Statistics are difficult in such a condition, but we have the impression that, indeed, these levels do not rise in these men and they have a favourable change of body composition and Dr. Schubert will talk about this further.
Blood pressure and pulse remained within a safe area.
So, in conclusion, the androgen substitution with intramuscularly injected testosterone undecanoate can maintain serum testosterone levels within the normal range and the injection intervals are appropriate when it is given from 10 to 14 weeks. That varies from individual to individual and therapy is well-tolerated. Of course, some patients may feel pain, not always but sometimes, for 2 to 4 days.
Major changes in erythropoesis and prostate size are seen during the first year of treatment and especially older men should be seen and controlled for these parameters at every injection; that means at every three months. Changes in bone density occur during the first 2 to 3 years of treatment.
And the treatment with testosterone undecanoate seems to have beneficial effects on body composition and lipids, maybe also diabetic patients would profit from that and investigational studies have been performed already. In this small cohort which I just showed, testosterone substitution was safe in long-term use. Thank you.
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