Excerpt From Varility Paradox Cause of PFS

Great insight from the new book…Androgen receptor Genes cause of pfs and sensitivity varies side effects he explains how this works below…

The official name for the group of symptoms Kevin and Lars experienced is post-finasteride syndrome (PFS), and perhaps one of the most troubling aspects was that it seemed so permanent, with the effect often persisting years after discontinuation of the drug. One clue to why that might be comes from animal studies, which in this case also tell us more about the feed-forward relationship between testosterone and the androgen receptor. A group of Italian researchers gave finasteride to rats and noticed that the number of androgen receptors in their brains went up.75 Moreover, the effects persisted long after the drug had been discontinued. To follow up on this finding, they then called in men with PFS, took skin from the penis, and found that the density of androgen receptors in men with PFS was about twice that of those without.76 Now, remember the idea of the testosterone bell curve and damping effects (little testosterone, little growth, more testosterone, more growth, even more testosterone, reduced growth)? I think this is what we are seeing here. With a greater concentration of receptors, the organ becomes more sensitive to testosterone and at a certain point, paradoxically, that sensitivity may shut down.† The Italian researchers have subsequently demonstrated that patients with either very short or very long CAG repeats in the androgen receptor suffer these effects,77 reflecting the complexity of this chemistry as well as the plausibility of this mechanism. Did Lars’s brain adapt to the blockade of 5AR by amplifying androgen receptor levels and, in turn, its sensitivity to testosterone? It’s possible. It does look as if, in response to the 5AR blockade of finasteride, the brain produces more receptors in order to become sensitive to lower levels of the hormones. This is a familiar concept to those of us who treat prostate cancer, for this is the same adaptation that cancer makes to survive after testosterone is wiped away. As we’ve mentioned in previous chapters, it is possible that having greater androgen-receptor activity could make you not only more sensitive to testosterone—for instance, causing levels to skyrocket, as they did with Lars—but also more sensitive to its absence. All this said, there are plenty of men out there who swear by the drug. Why does it work fine for some and not others? It seems possible that something about the subtypes of 5AR in the brains of these men is responsible for the variability in their sensitivity to inhibition with finasteride. I am also struck by the fact that this syndrome tends to manifest itself in young men who are taking low-dose finasteride (1 mg) and not older men who take the higher dose of 5 mg to combat prostate enlargement. Perhaps the changes that occur with age, as discussed in the previous chapter, have something to do with this, or perhaps it is another bell curve. We’ve seen throughout the book that anytime you manipulate a piece of the testosterone system, you risk unexpected changes. The important difference, to me, is that in the case of using finasteride for baldness, this risk is not a necessary trade-off to treating a deadly disease like prostate cancer; it’s the cost of treating a receding hairline.


Great post my friend, im curious has the androgen receptor density been tested anywhere else besides penile tissue? I think my skin body wide has been effected the same way penile tissue has in these studies, I’d love to test that and see if im correct or completely wrong, how did the scientists in the study’s check for this? I’d love to be the guinea pig on this one, it’d definitely help strengthen the theory accutane works on the same mechanism if i did have a lot more receptors i think? As i said im no scientist and I’m sure someone has thought of this already but if they haven’t, let me know :blush:

I’ve long thought it significant this is extremely rarely happening to older men, even within how astonishingly rare PFS is at all. The recent FAERS data review showed that there were far less adverse reactions happening to older men taking fin, and when they did occur they were not associated with disability in the same way. Furthermore, doctors were over doubly more likely to be the ones reporting the adverse event reported by an older man, whereas the younger men’s cases - more disabling - were left to be self reported in the main. I could speculate this is probably because when an older man gets a side or two it’s within what the doctor considers a logical reaction to a drug, and because PFS is sometimes so completely physiologically devastating, sometimes degenerative, and in the most susceptible takes a very brief use of a 5ari to onset, they often don’t seem to believe it possible.

There’s a rat study I can dig out if anyone wants it that shows there is a vast change in the expression of 5ar throughout tissues as they age. Imo this could have some significant contribution.


Maybe younger men, whose bodies are still growing and adapting to hormones, have a greater reaction to the sudden dip in DHT? Their bodies are still ‘plastic’ (to use a term from neuroscience) in that they are still highly malleable and when an androgen plummets, they have a massive over-expression of the AR. Whereas older men have a more stable hormonal system that is, if anything, waning in potency and not as reactive.

The question remains, how can one reduce the over-expression of the AR?

where is this excerpt from?

It is from Charles Ryan’s new book as stated the “Varility paradox”…I also believe and some studies have hinted at this that mg dosage varies the effects for some reason…Most older men have more androgen receptors and lower hormones naturally and are on 5mg or cut dosages…I myself had a completely different experience on the generic proscar than the 1mg propecia both while on the drug and after stopping…

the bell curve theory is nuts. i seriously believe in it to be what is causing our issues

Do we have any possible thoughts on the best way to combat this? Hypothetically at this point obviously

well, not increasing androgens for you guys would be a good start to “combat” this.

in terms of a cure, i don’t know. it’d be something to lower receptor expression. we don’t know what’s causing overexpression yet

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