Lecture on penile changes caused by androgen deficiency

agingmale2006.com/transcript … ecular.asp

Describes mechanisms in detail by which androgen maintains penile tissues. Of particular interest:

So our framework works as follows – testosterone can be metabolised into 5- a DHT by the 5- a reductase, and either 5- a they had with testosterone or testosterone would bind to the androgen receptor. And binding to the androgen receptor in the corpus cavernosa will illicit metabolic function including activation of the neural nitric oxide synthase (nNos), endothelial nitric oxide synthase (eNos), expression of PDE-5 and many others. Also, the androgen receptor will regulate changes in the nerve fibres, smooth muscle content, connective tissue deposition, and, an interesting observation we made recently, is the regulation of the adipogenesis, or the pathway of the lineage of the fibrostroma progenitor cells going either into smooth muscle cells or into adipocytes. When you have healthy erectile tissue you have a functional veno-occlusion. So therefore our endpoint, or our outcome measure as you will put it in your clinical setting, is the veno-occlusion dysfunction. So, if everything is going smoothly, veno-occlusive function is working. If any alteration in the metabolic or structural component of the tissue is altered due to androgen deficiency or androgen insufficiency or androgen deprivation, the veno-occlusive function will malfunction, and if that is the case, there will be no erection.

All the studies I am going to show you are animal model studies. That is why I am taking you from your clinic into the laboratory. Let’s look at the veno-occlusive function. Here is a group of male rabbits, which are intact, and if we look at the intracavernosal pressure in response to electric field stimulation of the cavernosal nerve you can see that there is a nice increase in the intracavernosal pressure. If you castrate these animals two weeks later, if you repeat the experiment, if you stimulate the pelvic nerve you can see that there is no trapping of blood because due to androgen deficiency, due to castration, something happened, both metabolically and structurally. Therefore the veno-occlusive function malfunctions or failed, and therefore no trapping and no erection. If you take a group of animals, which were castrated and now you treat them back with androgen, you actually recover. So this is a reversal process within that frame of time. If you give them oestrodial instead of testosterone, you do not recover the veno-occlusive function. Therefore androgen is absolutely critical, at least from this point of view, for maintaining the veno-occlusive function. Why? Because we believe that it maintains many aspects of the metabolic and structural components, as I will show you in a few minutes.

If you look at the red or pink stain it represents the trabecular smooth muscle, and that is the control. Look what happens when you deprive the animal from androgen, there is considerable reduction in the trabecular smooth muscle, and there is increased in the blue stain, which represents the connective tissue. What does that mean? It means you are losing tissue compliance. The fewer smooth muscles the fewer smooth muscle that can expand, relax and expand, therefore, you actually are altering tissue compliance. If you are altering tissue compliance you are not going to impede blood outflow and if you cannot impede blood outflow you are going to have what we call venogenic leak or vasculogenic impotence as shown by Dr. Tom Lue and Dr. Rogers. I think that is what we believe is happening here. There is a reduction in trabecular smooth muscle and there is an increase in conductive tissue deposition. What happens when you give back testosterone? So you give this group testosterone and you go back here and now you can see that almost they are similar. So this is a reversible process. I think that is good news in a sense that maybe within this frame of time, that this loss of smooth muscle can be recovered by giving back androgen, but not by giving back oestrogen.

So, as we’ve heard before, this is a reversible process. The fact that the author here warns repeatedly that testosterone replacement is effective “within a frame of time” means that it is probably wise to seek treatment ASAP in order to return testosterone, and penile structure, to normal.