Finasteride Losing Effect Over Time And Androgen Receptor Upregulation

[GoldenMane]

If anything, men with low testosterone are more likely to experience upregulation since both their Androgens, testosterone and DHT would be low. Probably also more likely to experience side effects from finasteride or dutasteride. Men with high testosterone will still have high androgens (even higher testosterone, lower DHT) on finasteride so are less likely to result in AR receptor upregulation. If this is true, then the best way to fight upregulation is to keep testosterone high and DHT low. If testosterone gets lower (happens naturally with age) then overall androgens will decrease not just DHT which may result in more sides and AR upregulation. Perhaps keeping testosterone in a normal healthy range while using strong DHT blockers to prevent DHT formation would be a good way to inhibit sides, prevent AR upregulation by keeping overall androgens high and maintain hair. Based on this theory, men should monitor their testosterone levels and if they get too lower, maybe try hormone replacement therapy.

 

[WangMQ]

If anything, men with low testosterone are more likely to experience upregulation since both their Androgens, testosterone and DHT would be low. Probably also more likely to experience side effects from finasteride or dutasteride. Men with high testosterone will still have high androgens (even higher testosterone, lower DHT) on finasteride so are less likely to result in AR receptor upregulation. If this is true, then the best way to fight upregulation is to keep testosterone high and DHT low. If testosterone gets lower (happens naturally with age) then overall androgens will decrease not just DHT which may result in more sides and AR upregulation. Perhaps keeping testosterone in a normal healthy range while using strong DHT blockers to prevent DHT formation would be a good way to inhibit sides, prevent AR upregulation by keeping overall androgens high and maintain hair. Based on this theory, men should monitor their testosterone levels and if they get too lower, maybe try hormone replacement therapy.

Mane, your hypothesis is interesting. I'm quickly skimming through my memory and it does seem that a lot of long term success stories on our forum mentioned that they had the same or even higher libido after taking finasteride, suggesting high T. Some of them have highly masculine features too. I, on the other hand, did experience slightly lowered libido, and I don't think I have high T level (I don't have a lot of body/facial hair)

It's still just a hypothesis though. And DHT is supposed to be way more potent at binding to ARs. But I guess maintaining a good T level can't be bad to your health. It also helps fighting sides. Maybe taking aromatase inhibitors would benefit.

 

[WangMQ]

I don't remember for sure, but I think people suggested topical setipiprant in the morning to reduce the sleep problem.

Kythera is trialling 1mg seti in the morning and at night, we'll have evidence they're an honest company if sleep problems are discussed in their phase II trial results.

By the way when I had my "trying finasteride thread", people were telling me the sleep problems were in my head.

Interesting that fish oil inhibits PGD2. I didn't know that, I take fish oil everyday as it's excellent for general health. I will start taking it in the morning instead of at night. Maybe that will benefit my sleep.

This PGD2 discussion is off topic but:

I read some posts about seti. It does seem to cause sleep problems. Maybe the PGD2/CRH2 angle is another death end: to suppress them to the level low enough to prevent hairloss would inevitably lead to sleep problems.

If so, that's one more big thing with high hope down in our future.

 

[WangMQ]

I really hope you're wrong about AR upregulation, but if that is the case, I'm sure a two pronged approach as suggested with an AE antagonist could help. I've read that Retin A and EGCG from green tea, selenium can downregulate androgen receptor activity.

Also found an article on androgen receptors being downregulated due to Androgen deprivation, though that was in prostate cancer cells. There are quite a few studies on androgen receptor downregulation as a means of treating prostate cancer, many of the treatments result in cell death in cancerous cells though I'm not sure what affect they may have on healthy prostate,or more importantly hair follicle cells.

Retin A does seem an option, but it's proven to have severe sides. No good playing with it unless we're desperate.

I read that about green tea too. I already drink a lot of green tea actually but I doubt if the benefits from diets/supplements can really do anything major. The pro-natural forums like Immortal Hair has a lot of guys going that angle. I'll keep drinking it though since it's good to your health anyway.

updates: I read the study again. It doesn't really down regulate ARs, just competitively binds to them.

 

[GoldenMane]

My hypothesis also explain why finasteride stops working with age and why eunuchs when given testosterone go bald at a faster rate. High androgens means no AR upregulation. Low androgens means upregulation happens. How do we prevent upregulation? Keep our androgens high. Then we use finasteride or dutasteride to ensure that the androgens stay as testosterone and not get converted. If upregulation has already occurred then I'm not sure if it's reversible so best to take a preventative approach and prevent testosterone levels from getting low and ensure that our androgen receptors don't increase. Honestly, this hypothesis explains everything...

 

[WangMQ]

Its funny on every debate about upregulation on ARs someone always cites studies from Marty E. Sawaya. She seems to be one of the only people that ever even looked into ARs which is odd given how critically important they are in male pattern baldness you would think researchers would look at that first.
Anyhow she was a fraud so I dont know how much of her work is true or not. She is being debarred by the FDA for getting a felony related to her field.

https://www.federalregister.gov/art...ary-e-sawaya-aka-marty-sawaya-debarment-order

"This offense was committed when Dr. Sawaya created a medical license by obtaining a copy of a colleague's Florida medical license, altered that license using a photocopy machine to reflect that the license was issued in her name, and submitted the false and fraudulent Florida medical license to the sponsor of a clinical trial, for which she was a clinical investigator. "

Ooops. Should've read that before posting the link. Thanks for the info.

Don't know for what reason she would've lied with that study though? Doesn't seem to matter her personal interest? Anyway it's good to take it with a grain of salt since you brought this up.

 

[WangMQ]

My hypothesis also explain why finasteride stops working with age and why eunuchs when given testosterone go bald at a faster rate. High androgens means no AR upregulation. Low androgens means upregulation happens. How do we prevent upregulation? Keep our androgens high. Then we use finasteride or dutasteride to ensure that the androgens stay as testosterone and not get converted. If upregulation has already occurred then I'm not sure if it's reversible so best to take a preventative approach and prevent testosterone levels from getting low and ensure that our androgen receptors don't increase. Honestly, this hypothesis explains everything...

I agree but again we need rigorous study before we can call it a theory. (Which is probably one century later when the bio-science community have finally come to their senses about what research topic to pick up)

 

[Afro_Vacancy]

I think it's interesting that setipiprant and finasteride share a side effect: reduced sleep.

I'd like to say that this is a good sign for the upstream recipe, but I'm hopelessly biased.

 

[GoldenMane]

I agree but again we need rigorous study before we can call it a theory. (Which is probably one century later when the bio-science community have finally come to their senses about what research topic to pick up)

It would be very easy to test, any of us could try, just monitor our testosterone, see if a drop in testosterone results in increases hair loss or see if testosterone replacement and dutasteride/finasteride can maintain hair indefinitely. No new drugs required. Just testosterone, dutasteride and blood tests.

 

[WangMQ]

It would be very easy to test, any of us could try, just monitor our testosterone, see if a drop in testosterone results in increases hair loss or see if testosterone replacement and dutasteride/finasteride can maintain hair indefinitely. No new drugs required. Just testosterone, dutasteride and blood tests.

With so many variables flying all over our current/past regimen and body predispositions...no, I don't think it's easy. We need large sample double blind trials with variable control

 

[GoldenMane]

With so many variables flying all over our current/past regimen and body predispositions...no, I don't think it's easy. We need large sample double blind trials with variable control

You're talking about a proper scientific study, nobody will fund that since there's no new drug to market, just finasteride, dutasteride and testosterone. A bigger problem is that it's a preventative idea, it's very hard to test a negative. The experiment would be trying to prove that high concentration of testosterone prevents androgen receptor upregulation... And that by adding an DHT inhibitor or antagonist, follicle miniturisation is inhibited indefinitely. Then again, The first part Im sure has already been tested in prostate research and the second part we already have a pretty good idea.

 

[Roberto_72]

My hypothesis also explain why finasteride stops working with age and why eunuchs when given testosterone go bald at a faster rate. High androgens means no AR upregulation. Low androgens means upregulation happens. How do we prevent upregulation? Keep our androgens high. Then we use finasteride or dutasteride to ensure that the androgens stay as testosterone and not get converted. If upregulation has already occurred then I'm not sure if it's reversible so best to take a preventative approach and prevent testosterone levels from getting low and ensure that our androgen receptors don't increase. Honestly, this hypothesis explains everything...

So the idea is that one should try to partake in all activities that increase testosterone so that up-regulation does not occur, provided that you use finasteride?
I can live with that.

 

[GoldenMane]

So the idea is that one should try to partake in all activities that increase testosterone so that up-regulation does not occur, provided that you use finasteride?
I can live with that.

That's my hypothesis, yes. HRT is also an option, we need androgens to remain high to prevent upregulation, namely testosterone, we don't need DHT. My one reservation may be that testosterone itself may also cause AA, not sure if it's true or not maybe it doesn't, maybe only DHT causes it. Assuming testosterone itself doesn't cause AA, this approach may actually work.

 

[GoldenMane]

That's my hypothesis, yes. HRT is also an option, we need androgens to remain high to prevent upregulation, namely testosterone, we don't need DHT.

Wang's idea about taking aromatase inhibitors is also a good one, prevent conversion of testosterone to oestrogen, maintaining high androgen levels and reducing the possibility of gynecomastia.

 

[Afro_Vacancy]

It's amazing we have no rigorous data on dutasteride+letrozole or whatever, it seems like an obvious thing to try.

 

[WangMQ]

I think the problem with T is that even supposed that T itself doesn't affect your hair, higher T + same 5AR level = higher DHT. There's no way you can bypass it.

 

[Dench57]

It's amazing we have no rigorous data on dutasteride+letrozole or whatever, it seems like an obvious thing to try.

Why would you want to take something as harsh as Letrozole long term unless absolutely necessary? It will f*** your hair in a way dutasteride can't protect (reducing aromatase/estrogen). It also comes with potentially nasty side effects with prolonged use.

 

[GoldenMane]

I think the problem with T is that even supposed that T itself doesn't affect your hair, higher T + same 5AR level = higher DHT. There's no way you can bypass it.

Umm... Finasteride/dutasteride? High T, very little is converted to DHT, AR upregulation doesn't happen because androgens remain high and testosterone competes with what little DHT is left for hair follicle androgen receptors. dutasteride is how you bypass 5A reductase activity, there's nothing missing, testosterone and dutasteride is all you need if my hypothesis is correct.

 

[Ventures]

I think it's not only upregulation of AR as we get old which makes Androgenetic Alopecia more severe, it's also cumulative exposure to even low levels of DHT (and both T and all other androgens ) over all that time. if upregulation of AR is huge problem, than, old people would have strong muscles, I suppose AR in all tissues would upregulate and they would have more juvenile body.

So, remember that finasteride block only 70-80% of DHT inside hair follicles, so the renaming part those 15 to 25% can also damage hair follicles, and that is what is happening for sure.

Another important thing is that as we get older, all cells in our tissues are older, they divide by much slower rate, there are less growth factors in our organism. We call that process senescence.

 

[Afro_Vacancy]

Why would you want to take something as harsh as Letrozole long term unless absolutely necessary? It will f*** your hair in a way dutasteride can't protect (reducing aromatase/estrogen). It also comes with potentially nasty side effects with prolonged use.

Any aromatase inhiitor, and you don't have to take the maximum dose.