Sponsored by an educational grant from Schering
Thank you very much, Mr. Chairman, thanks colleagues, ladies and gentlemen. We are going through the part of urology which is a little bit more interesting in showing data in terms of erectile dysfunction and we adjusted the presentation a little bit regardless the abstract because of time limitation. But I see we are good in time and I would like you to share me in a small experience I did in Germany as I moved by 1978 from Syria, Damascus, where I born, to Germany.
In the early ‘80s, I started my higher education in urology in Germany in (inaudible), which is a small city at the Dutch border and I took care of an old lady, mid-70s, at the department. I came in; I could not speak good German at that time. She looked at me and said, are you a stranger? I said, yes, ma’am. She said, but you look normal. I said, is that bad? But she looked very tenderly in my eyes and said, don’t worry, my son, the strangers are also humans. Okay, now I would like to share the experience with you with a long-acting testosterone undecanoate injections as a first-line therapy for patients with the two prevalent things: erectile dysfunction and hypogonadism.
We learned by 2003 from Dr. Morales that informational guidelines emphasised the need for screening for hypogonadism in patients with erectile dysfunction. It is essential.
And despite the fact that PDE-5 inhibitors delivered a revolutionary approach to therapy and diagnostics in terms of erectile dysfunction, but we still have a failure rate of 18% to 37% reported and that depends, obviously, on co-morbidities thereof, like hypogonadism in about 50% of the patients, diabetes mellitus, 35%, it depends on community and cohort you have and foods, nutrition habits, as well, it depends on LUTS of BPS in about one-fifth of the patients and hypertension in the small or in the same comportment.
If there are rationales for testosterone measurements or to screen hypogonadism and erectile dysfunction, the answer is yes. Fifty percent of non-diabetes patients are non-responders to PDE-5 inhibitors, they are hypogonadal; 42% of diabetes patients in our clientele are already hypogonadal upon diagnosing diabetes mellitus and 44%, according to Dhindsa in Buffalo of DM type II patients had hypogonadism.
And what does it mean for us? Typical urologists in the primary care setting that mean that both of ED and hypogonadism are prevalent and the population at risk includes those diagnosed with diabetes mellitus, metabolic syndrome, chronic renal failure or chronic diseases in general and aging, as well. In screening these populations we have men who can benefit enormously from testosterone therapy in this respect.
So started in the basic research in the nice, peaceful animal world. Shabsigh delivered the evidence that testosterone was so important for the penile tissues, not only for the brain, for libido, and published 1997 that in castrated rats, androgen deficiencies is going to cause apoptosis, that means fibrosis as well, affecting the fibro-elastic properties of the penis and the veno occlusion, as well. But the good news he delivered that if you give these rats testosterone or androgen again, you can reverse the changes you got in the penis. So it means they are going to get erections again.
Abdulmaged Traish, et al, they delivered also the evidence that castration and androgen substitution on trabecular tissues are a big deal and in castrated rabbits, Professor Traish gave the evidence that the compartment of collagen is going to be bigger in this ratio than smooth muscle and there is no erection because the fibrosis has lost its fibro-elastic properties of the penile tissue and rigidity in the lachrymal spaces, as well. But the good news here, also you can reverse this situation if you give substitution with testosterone.
And the hit is, what came up last year in the Journal of Andrology, and if I, Aksam Yassin, was or have been a member of the royal family of Sweden, I am going to give the gentleman the Nobel Prize for medicine and he delivered the evidence that testosterone modulates adipocyte accumulation in the penile corpus cavernosum. So it means there is some kind of accumulation in the sub-tunical area of fat cells which is in a small or minor imagination like small metabolic syndrome and that is going to affect enormously the veno occlusive function in the penis, leading to severe erectile dysfunctions because of venous leakage.
Now what does it mean if we summarise what we have seen in the animal models? There are a lot of studies; I picked only these three up. The animal models, androgen deficiency produces increased accumulation of the adipocytes in the sub-tunical region and in the corpus cavernosum in general. And the veno occlusive dysfunction here cannot be restored by PDE-5 inhibitor therapy alone and there is the non-responder to the therapy.
We got this idea after long discussion with Professor Traish and we wanted to look for proof of principle in the daily life in clinical experience, because I cannot cut penises of the gentlemen they come to therapy to us or take biopsies. I am in trouble with the medical council in this case. And so we took a cohort of 23 patients of ours with severe, a little bit moderate erectile dysfunction, T of 12 in some cases, and they, 12 IIEF I mean, and we, and there were non-responders to PDE-5 inhibitors and also non-responders to injections, the cavernosal injections of prostradiol. And we did the diagnostic info and the Cavernosography and this came up as a case report in the Andrologia in this issue in February was also published. And we see that opacification of that cavernosal tissue is different. There is something of irregularities here and we see, we suggest it could be that an accumulation of adipocyte affecting the veno occlusive function and consequently we have also deep venous leakage in this patient. It is one example. We found that in 12 patients from 23 and we give these patients testosterone therapy, in this case Nebido®, according to the protocol: day 1, week 6 and every 3 months adjust it a little bit and we found after 3 months, no venous leakage at all and better opacity of the cavernosal tissues here. We got this at 6, it is just an example, in 5 patients to now and other 7 are still under full ob.
I go back now to the primary care section. We are not going to deliver a Cavernosography to each patient who is coming to us with hypogonadism and erectile dysfunction. What we do here in the primary care section, we know that in urological office that erectile dysfunction is a key symptom to diagnosing hypogonadism. That’s an issue and we screen 771 patients at our clinic with ED under therapy within the last 2 years. And we found that 141 patients, it is a cohort or amount of almost 50, one-fifth of the patients, they are hypogonadal, 18.3%. We put 122 patients under injection with Nebido®, long-acting testosterone ester. Other 10 patients, they received Testogel because anti-coagulant therapy and 9 preferred, according to patient preference only, to take the injection, testosterone enanthate. And we assessed here the impact of long-acting testosterone injection alone to restore erectile function in these hypogonadal men.
And the methods after assessing, we found hypogonadism in average age, 56 years, testosterone level under 3.4 ng/mL and the follow-up time was 3 to 11 months, in average 8 months.
Lab included complete blood count, total testosterone DHT, lipid profile, blood sugar, as usual, and physical sonographic examination was important and prostate safety parameters also were included in that programme and follow-up protocol. Sexual function was assessed by initial tests in erectile function at baseline after 18 months and every 3 months in these patients and the time average of ED, 3.6 years, and main baseline testosterone level was 1.9 plus/minus 0.5, a different range, we have it here, in our lab, 3.4 to 8.6.
Now, if you look at results here, in this cohort of patients, we see that at the baseline the patients they had modest but small severe erectile dysfunction, but after 12 weeks, we have a response average of 54% of the patients, 66 patients from 122. But in the long control time, so we could jump from 54 to 58, which is not really big significance in the therapy see what it means, if you got the control here, you continue with testosterone therapy because of hypogonadism or erectile dysfunction, it is a lifetime therapy. By the way, you are going to get the improvement, actually, after 3 months, that is going to stop and it is fine. You had a cohort of patients, 42% they are non-responsive to this therapy.
What is happening to the parameter of erectile function domain? They jumped from 12 to 25 in average after 12 weeks and consistently in the following time and sexual desire domain was jumping from 4.5 to 8 and, remarkably here, after 6 weeks of the therapy.
Now look at me, if we are going to enlight the issue in non-responders, the IIEF score is very miserable. It jumped only 2, which is statistically not significant, even in descriptive way, but sexual desire domain was improved from 4.5 to 7.5.
I would like to show you only the co-morbidities, not in the whole group, only in hypogonadal patients in general, in our group and the people that didn’t respond to testosterone therapy in terms of erectile dysfunction. So we see the cohort with diabetes mellitus, we have totally 45% of that total subjects, hypogonadal subjects, and in non-responders, we have here 49%. Hypertension, we have here as a co-morbidity in this cohort, 42% of the patients but in non-responders, 64%, so it means that co-morbidities are so severe that speaks obviously for the multifactorial pathophysiology of erectile dysfunction and dyslipidemia jumped from 31 to 58, LUTS/BPH from 32% to 70%.
So, if we conclude, we can say that testosterone therapy alone can restore erectile function in the majority of the hypogonadal patients in this group. Testosterone could be considered as the first line therapy in patients with hypogonadism and erectile dysfunction. Further evaluation in comparison with control groups will enlighten the influence of testosterone therapy alone. In non-responders to testosterone alone, the combination therapy here with PDE-5 inhibitors is surely recommended.
I thank you very much for paying attention.
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