Cycling off Propecia to reverse tolerance

[Britannia]

I totally reject the idea of finasteride tolerance. If we became tolerant to finasteride then how can people successfully take Proscar to treat BPH, and remain on it for decades without a reoccurance of symtoms? Finasteride successfully maintains its ability to keep DHT levels lowered over long periods of time and this allows a reduction in prostate size. But long term reduction of DHT does not allow for the preservation of hair follicles over a similar time span to that of prostate size reduction. I suppose upregulation of DHT occuring in the hair follicles only would explain the phenomina I described. But there is no logical biological reason to explain why a hair follicle would want to upregulate DHT (or there is but it hasnt been discovered yet). Maybe the answer lies in the theory of an increased level of auto-immune activity against a hair follicle over time. Anyone got any thoughts here.

 

[Weepy]

Precisely. You couldn't have made my point better.

In the mechanism you use as an analogy, it makes sense your body would upregulate LDL receptors because your cells NEED LDL. Now if you are going to argue that your cells need DHT, and that your body upregulates all receptors, including those in your hair follicles (to our dismay), in order to get DHT where it is needed, then I'll buy that. But I don't think that's the case. While it is possible there may be some function for dht beyond puberty, i think your body gets all potential dht requirements even at finasteride reduced levels.

I understand people want an explanation for reported cases of "finasteride tolerance." I think a better explanation is that as people get older, their receptors get more sensitive to DHT simply because they are genetically predisposed to do so. At some point, that sensitivity reaches a level where even with reduced DHT from finasteride, you are going to start losing your hair again.

I think I see where our differences actually lie.

It's not a matter of "need." Our cells are simply responding to chemical cues. That's about as philosophically complex as it gets.

I can't speak to physiolgoically significant levels of DHT, i.e., "your body gets all potential dht requirements even at finasteride reduced levels."

 

[Weepy]

But there is no logical biological reason to explain why a hair follicle would want to upregulate DHT (or there is but it hasnt been discovered yet). Maybe the answer lies in the theory of an increased level of auto-immune activity against a hair follicle over time. Anyone got any thoughts here.

Don't confuse the issue... DHT is the signal, the hormone. The upregulation refers to upregulation of the actual gene for the Androgen Receptor. Upregulating essentially translates into more androgen receptor.

People who study this sort of thing are in a field called signal transduction. What's interesting is that the key genetic players involved are evolutionarily conserved across species. But I'm already venturing outside of my area.

 

[Private Ryan]

personally i do not think that you can develop tolerance to finasteride. it get into your blood stream and zap any DHT it encounter on it way. your body is unable to produce "super DHT" that is resistant to finasteride. of course, it is a know fact that finasteride decrease it efficiency as time goes by, more for those that do not response well to finasteride and less for those who response well to it. the reason could be other thing and less likely due to tolerance.

 

[Britannia]

personally i do not think that you can develop tolerance to finasteride. it get into your blood stream and zap any DHT it encounter on it way.

Wrong. Finasteride does not "zap" or "block" or "inhibit" or do anything else at all to DHT. Finasteride is completely incapable of interacting with DHT in anyway. Finasteride works by interfering with the synthesis of DHT from testosterone and it does this by inhibiting the enzyme type II 5 alpha reductase.

 

[Dinzy]

I totally reject the idea of finasteride tolerance. If we became tolerant to finasteride then how can people successfully take Proscar to treat BPH, and remain on it for decades without a reoccurance of symtoms? Finasteride successfully maintains its ability to keep DHT levels lowered over long periods of time and this allows a reduction in prostate size. But long term reduction of DHT does not allow for the preservation of hair follicles over a similar time span to that of prostate size reduction. I suppose upregulation of DHT occuring in the hair follicles only would explain the phenomina I described. But there is no logical biological reason to explain why a hair follicle would want to upregulate DHT (or there is but it hasnt been discovered yet). Maybe the answer lies in the theory of an increased level of auto-immune activity against a hair follicle over time. Anyone got any thoughts here.

Why not consider the simplest explaination? finasteride reduces DHT but it is still there in your bloodstream only in lower concentrations. Over time this DHT can still do it's dirty work, only more slowly. Or once balding starts it will continue regardless of DHT concentration, only the rate will increase proportional to the ammount of DHT present.

If this is what is going on then finasteride merely provides an offset and a slow down of male pattern baldness. The offset comes from the initial drastic reduction in DHT when starting treatment and the slowdown from its continually low level thereafter. I wish I had somwhere to upload a graph to better illustrate my point, but perhaps I can get through with just words. As far as the graph goes I was thinking that the Y-axis would be hair count/density whatever and the X would be time. And then for simplicity I would keep every dependance purely of the form H=a*t+b, though clearly this is an oversimplification the argument carries over to other functional forms. H is hair count, a is change in hair count in time, t is time and b is the offset. SO for the normal balding person his hair count, Y0 would have the functional form H= -B0*t + H0. Here -B0 = initial balding rate and is a negative number and H0 is how much hair he has at time = 0. Now the effect of finasteride can be modeled in the same way H=Bf*t + HF where BF is a positive number because finasteride helps with hair count and HF is also positive and is the offset provided by dropping finasteride. You could model minoxidil in the same way or perhaps just a H=HM=constant. The net graph for a person is Hair = (Bf-B0)*t + H0+HF. Here Bf-Bo is stll a negative number because we are all screwed in the long run but initially the person has more hair and over time he will lose it but at a reduced rate. Bf-B0 accounts for all other causes of male pattern baldness including immune system and remaining DHT.

This simple idea accounts for several observed phenomena. Since the offset and slow down rate clearly depend on the individual this can explain why some actually grow hair on finasteride while others merely maintain. If the offset effect is high in an individual then his follicles will be able to produce better hairs at first. If not then that probably means the offset is about equal in magnitude to the loss experienced while waiting for finasteride to kick in. It also can explain why some seem to slow down their loss but don't stop it completely. And it allows for finasteride to appear to loose it's effectiveness over time.

I know nothing about BPH but perhaps it has no external cause other than DHT or that the leading term modelling all those causes plus the postitive impact of finasteride is too small to notice in a lifetime or positve or zero.[/img]

 

[Britannia]

Over time this DHT can still do it's dirty work, only more slowly. Or once balding starts it will continue regardless of DHT concentration, only the rate will increase proportional to the ammount of DHT present.

That isnt true. Once balding starts, it does not necessarily continue regardless of DHT concentration. If this were the case then why do some people who take Propecua manage to not only stop male pattern baldness, but REVERSE it. I think the figures from the FDA were about 69% experienced some regrowth. So we can deduce from this that 69% of people acutally STOP the balding process completely because DHT concentration has been lowered to such a point that it is incapable of doing "its dirty work".