Treatment options for PADAM syndrome or late onset hypogonadism

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Svetlana Kalinchenko, PhD interviewed by Professor Bruno Lunenfeld, MD  

Prof. Bruno Lunenfeld, MD: My name is Bruno Lunenfeld. I’m an Endocrinologist and I am the President of the International Society for the Study of the Aging Male. It is my great pleasure today to interview one of our lecturers, a faculty member, who gave a very interesting lecture this afternoon, on the possible factors in the pathogenesis of the Partial Androgen Deficiency syndrome, (PADAM). Her name is Svetlana Kalinchenko and she is the Chief of the Department of Andrology at the Endocrinological Research Center, Moscow, Russia.

I have a number of questions for you. They are not directly related to your lecture of today. You did a very important job by demonstrating, for the very first time in 2001, that the combination of sildenafil, and testosterone, is very useful in non-responders to erectile dysfunction specific therapies. The presence of testosterone may be an important factor in eliciting response. So, could you please tell us how did you come to the idea to combine testosterone with, sildenafil and what made you do this?

Svetlana Kalinchenko, PhD: Thank you very much for such an important question! We are very proud of our study because it seems to me that this study opened a new era. It opens the era of combination treatment for erectile dysfunction. This idea came from our clinical practice. Because I work in the largest centre in Moscow, The Russian Centre for Endocrinology, and I have a lot of patients. Five years ago Pfizer came to us and asked us to try Viagra for the treatment of erectile dysfunction. When we noticed that some patients are non-responders to Viagra, we decided to find out why. Maybe there are some reasons for non-responders.

Because I am, like you, also an Endocrinologist, I decided maybe these patients have some hormonal factor which can explain the inefficacy of Viagra. We know very well for efficacy of Viagra, patients should present with sexual stimulation. As said, maybe it was some problem with sexual stimulation, because we know from our patients with hypogonadism, they have significantly decreased libido. That’s why we started to investigate the level of testosterone, and we found that the level of testosterone was lower in the non-responders. 

When we asked our patients how they used Viagra, they were very well instructed. They just swallowed the Viagra and awaited the results, without any sexual stimulation. All endocrinologists know that it is difficult to imagine the patients with a very low level of testosterone will be able to have a sexual stimulation.

After this we tried to combine androgen with sildenafil and had good results. We are very proud that a lot of researchers in different countries repeated our study and also have shown good results. 

Prof. Bruno Lunenfeld, MD: I was very impressed because already in 2001, at the first Asian meeting in Kuala Lumpur, you presented this data. It is now being confirmed by so many people, even during the lectures here. I think to combine androgen with sildenafil is essential when treating sexual dysfunction in men with.

Now tell me something of your ideas on your lecture this afternoon on the pathogenesis of PADAM. Can you just repeat, for the audience who were not here, just in a few words, how you came to this, and what do you really think, with our present knowledge, is the pathogenesis of PADAM, of Partial Androgen Deficiency syndrome, or late onset hypogonadism?

Svetlana Kalinchenko, PhD: I would prefer late onset hypogonadism because it is more correct. If we use PADAM syndrome, PADAM is Partial Androgen Deficiency in Aging Male, maybe it’s just physiological condition. If we use this term it doesn’t mean we should treat every patient with PADAM syndrome. But if we accept the definition hypogonadism, that means that we should treat every patient, because hypogonadism is a pathological condition, which needs therapy, like all pathological conditions, or like another endocrine deficiency.

Prof. Bruno Lunenfeld, MD: All endocrine deficiencies with clinical consequences should be treated. It really doesn’t matter if a diabetic comes with the age of 50, or the age of 80, you will treat them. The same is true for patients with hypothyroid. So you believe that when somebody comes with hypogonadism, whatever his age is, and there are symptoms, and they are confirmed by the laboratory results, you will treat them. 

Svetlana Kalinchenko, PhD: Yes, of course. We try to find the correct therapy. We try to find the pathogenesis of late onset hypogonadism, and now we know that up until 70 years of age, the testes can produce testosterone. That’s why we are now commencing a new approach to the treatment of patients with late onset hypogonadism; stimulation therapy, with help of hCG. It’s therapy that stimulates the testes to produce testosterone. This therapy has a lot of benefits since it maintains the volume of the testes as well as spermatogenesis. 

Prof. Bruno Lunenfeld, MD: It also, may I add, helps your diagnosis because it will estimate the functional capacity of the testes. If the testes still has functional capacity, it will respond with a significant increase of testosterone. In such cases, you will treat the patient with hCG. If the functional capacity, or the testes with hCG does not respond, you will treat with testosterone, is this correct?

Svetlana Kalinchenko, PhD: Yes, this is correct and it has opened an additional possibility for treatment.

Prof. Bruno Lunenfeld, MD: So the algorithm, you will agree, I think, is that if we suspect late onset hypogonadism by the symptoms, by questionnaires, and by clinical examination, and we confirm it by laboratory tests, then we probably have to do an hCG test. If the hCG test is positive, you may, for a certain amount of time, continue to treat this patient with hCG, maintaining as you said, very nicely, the testicular size as well as spermatogenesis. The moment that the testes will not respond anymore to hCG stimulation, you initiate testosterone therapy.

Svetlana Kalinchenko, PhD: Yes, you are right. 

Prof. Bruno Lunenfeld, MD: With this, I think we can conclude this interview. I think it was very nice and I congratulate you for your work, as young as you are, you have a very big future and we all wish you the very best.

Svetlana Kalinchenko, PhD: Thank you very much Bruno. All ideas come to younger researchers when we see such famous, so professional research. It is thanks to you. Thank you very much!