Soon I hope I will be able to write a detailed post trying to explain why I think I suffered a serious crash after I discontinued tissue application of DHT for 48 hours (but not systemic application). This is yet another extremely important piece of evidence that I wish I didn’t have. I will explain later why this is so important.
For now I will briefly attempt to explain the potential mechanism behind this crash, and more importantly, I believe, behind PFS in general. Keep in mind that this is an extremely schematic model which no doubt omits many intermediate steps and processes.
The most important factor to keep in mind is that DHT appears to positively upregulate 5ar expression - i.e. more DHT leads to higher expression of 5ar and even higher production of DHT, and vice versa. This is confirmed by the literature and I will cite references later.
Such a regulatory mechanism may appear paradoxical but it is not because there is another component in the regulatory system - namely the androgen receptor. The AR exhibits negative feedback - it gets downregulated when androgens are high and vice versa.
The two regulatory mechanisms, 5ar and AR, work in tandem to regulate the system. There is indeed evidence that DHT upregulates 5ar through the AR. When there are two components in the feedback system, only one of them needs to be capable of negative feedback, and this is the AR.
Here is how it might work. A reduction in, say, testosterone leads to lower production of DHT, which downregulates 5ar, which reduces DHT even further. DHT is halted from plummeting uncontrollably by upregulation of the AR, which increases androgen signal and upregulates 5ar back up until an equilibrium is reached.
However, if DHT falls too much and too suddenly, which is what I believe happens in PFS and also during a crash, the AR does not have enough time to upregulate itself in time to stop the rapid downregulation of 5ar. Once 5ar is silenced significantly, DHT is at a critically low concentration and even the subsequent up-regulation of the AR cannot shake the system out of the new bad equilibrium.
The reason I think I suffered a crash is because during the months of local DHT application to the tissues, the AR must have been downregulated relative to its preexisting state. When I withdrew the DHT, first there was a rapid drop in DHT, which is dangerous as described above, but also the resultant androgen signal in the tissues dropped below what it was before I started DHT administration (assuming there was no upregulation of 5ar by the DHT in the meantime, although this condition can be relaxed). Thus, 5ar was donwregulated even further (relative to PFS baseline) and I was left at a worst state than I had been before I began DHT administration. Now my regular DHT dose does not work any more.
Caveat: I have no illusions that this model is too simplistic. It absolutely is. The important thing is that it makes roughly the right predictions, which I think it does.
I believe this is the first time such a theory of PFS has been proposed. I am not particularly attached to the pieces attempting to make sense how PFS happens. Those may very well be wrong or be a lot more complex.
However, I feel fairly confident about the model’s predictions of when PFS happens (or at least what I refer to as PFS type 2) - i.e. in conditions of rapidly falling DHT or any conditions where the AR (and any intermediate processes) cannot keep up opposing downward pressure on DHT. I have written about this at length earlier in the thread and elsewhere.
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