Finasteride can upregulate Androgen Receptors

[Mens Rea]

Finasteride upregulates expression of androgen receptor in hyperplastic prostate and LNCaP cells: Implications for chemoprevention of prostate cancer

1. Ju-Ton Hsieh,
2. Shyh-Chyan Chen,
3. Hong-Jeng Yu,
4. Hong-Chiang Chang

Article first published online: 12 JAN 2011

Abstract
BACKGROUND

Although finasteride is recognized for its role as a chemopreventive agent for prostate cancer, higher grades of malignancy have been reported. It is questioned whether blocking of testosterone conversion to dihydrotestosterone (DHT) by finasteride in prostate tissue will change expression of androgen receptor (AR). Therefore, this study evaluated the effects of finasteride on AR expression in prostate tissue and in the LNCaP cell line.

METHODS

Between January and December 2006, we retrospectively selected and evaluated 47 cases of benign prostatic hyperplasia treated with variable duration of finasteride (5?mg QD) before transurethral resection of the prostate. AR expression in prostate tissue was semiquantified by immunostaining and compared with duration of finasteride treatment. An androgen-dependent prostate cancer cell line (LNCaP) was cultured in charcoal/dextran-treated FBS with DHT or testosterone, and treated with finasteride for 1–3 weeks. Samples of total RNA were collected to analyze expression of AR by real-time quantitative reverse transcription polymerase chain reaction.
RESULTS

Immunohistochemical study revealed significant upregulation of ARs by finasteride treatment for 30–180 days. In cell line study, quantitative real-time reverse transcription polymerase chain reaction revealed significant upregulation of ARs treated by finasteride.

CONCLUSIONS

In our study, finasteride influenced AR expression in benign prostate tissue and prostate cancer cell. Before we can use finasteride in chemoprevention with confidence, we still need to clarify the influence of finasteride in ARs and its regulation pathway. Prostate © 2011 Wiley-Liss, Inc.

http://onlinelibrary.wiley.com/doi/10.1 ... 5/abstract



This is why a few guys on propeciahelp are CONVINCED they've suffered from changes in gene expression whereby their androgen receptors in prostrate/penis have been completely mashed. Awor and Mew believe that with some PFS victims, their androgen receptors have become more sensitive due to the DHT defeciency that their recptors have experienced from finasteride, when these guys stop finasteride the new rush of DHT to the newly upregulated androgen receptors overwhelms the receptors. This, in their view explains why the "crash" is so common (usually a matter of days or weeks from cessation) as the receptors become damaged now they are upregulated. Essentially, in their newly refined state, they can't handle the DHT levels, anymore....certainly now a random burst of DHT after a sustained period of potential deficiency.

This would explain why some guys have perfect hormone levels but yet have all the sides of PFS. It's complex but studies like this support why some guys appear androgen resistent. Some guys can take TRT without noticing anything, for instance.


Have a read.

 

[Wuffer]

This is interesting for sure. I hope it paves way for some more studies that can more conclusively prove that this is the case, as well as identify the risk for the average finasteride user.

Based on this, it indicates that it may good practice for the guys to wean off finasteride should they choose to quit. There isn't a perfect way of doing this, but the practice in the follwing link would probably be the best:

viewtopic.php?f=46&t=65022


I'm not convinced that PFS exists, but i'm not saying it doesn't either. This would be a good potential cause for these problems for sure, and could potentially explain the 'crash' people describe. If you slowly re-introduced DHT to your system through weaning off over the course of a couple months, I would expect one could avoid this crash.

 

[Mens Rea]

This is interesting for sure. I hope it paves way for some more studies that can more conclusively prove that this is the case, as well as identify the risk for the average finasteride user.

Based on this, it indicates that it may good practice for the guys to wean off finasteride should they choose to quit. There isn't a perfect way of doing this, but the practice in the follwing link would probably be the best:

viewtopic.php?f=46&t=65022


I'm not convinced that PFS exists, but i'm not saying it doesn't either. This would be a good potential cause for these problems for sure, and could potentially explain the 'crash' people describe. If you slowly re-introduced DHT to your system through weaning off over the course of a couple months, I would expect one could avoid this crash.

Not sure how you can even contemplate that PFS doesn't exist, but whatever.

You have to bear in mind that the people that stop the finasteride are usually the people who couldn't tolerate it in the first place so there would appear to be a link between this potential androgen receptor upregulation and the people who can't tolerate it and later develop PFS.

I'm just not convinced one could accurately ween of the drug unless under extensive medical oversight (obviously not practical) but it could be worth a try. There are plenty of guys on PH who tried it unsuccessfully.

 

[Wuffer]

It's sort of hard to explain my viewpoint. I'm not exactly saying it doesn't exist. I admit that it could exist.. And talking to you and a bunch of other guys sort of convinces my 'emotional' mind to say that it does exist.

However, I’m a very scientific minded guy. I might not know a lot about biological sciences per say, but I know a lot about computer science. I am also an atheist. I base my decisions on evidence that meets my personal level of criteria. I was raised that way, and that's how I live my life…

Right now, I don't believe there is sufficient evidence that proves finasteride can cause permanent problems. There is much evidence to the contrary. However, I don't have any emotional attachment to the drug. Should this evidence come out tomorrow, would likely drop it. Your personal story, as well as many others, are certainly troubling to me as a finasteride user. I don't ever make light of your situation, but I hope you can understand why I can't use your experiences as evidence to base my own decisions on. I really hope you can appreciate where I’m coming from. I hate arguing like we do; it’s really not in my nature. For the tenth try at this, we should all just try to agree to disagree

Back to the topic at hand, it's difficult to wean off finasteride by cutting it into smaller and smaller doses. Once you go below that flat dose response, you are back to DHT in full force. I think the technique I presented is a little better at slowly introducing your body to DHT. Taking into account the short half-life of a regular finasteride dose (a little over a day), when you start not taking it for several days at a time, it makes sense that it would be a more gradual introduction to DHT in your system.

You are right though. It seems that everyone who quits finasteride will quit because they were experiencing side effects. If the side effects were caused simply by the lack of DHT (and not some other farther reaching complication of 5AR inhibition) then this could definitely explain why this crash was experienced.

This is a ridiculous theory admittedly, but I’ll throw it out there even though I’m sure you guys will berate me. . Let's say the weaning technique I posted about was accurate; it slowly introduces DHT back into your system over the course of a month in a nice smooth curve. If your body simply couldn't handle the sudden increase of DHT from quitting cold turkey, then if a PFS sufferer went back on finasteride for a couple months and then weaned off, could it be possible for this slow introduction of DHT be enough to 'reset' your body’s response to it?

 

[Ende]

So finasteride upregulates androgen receptors, but I don't believe that they get downregulated when the DHT level increases again. It makes no sense. You don't see a downregulation in people who're abusing steroids which are much more anabolic and androgenic than both testosterone and DHT. Take a look at Halotestin.

What's perfect hormone levels? They don't have a clue, because it's all about ratios, and the optimal range is narrow, especially in relation to testosterone and estrogen. Your brain, penis, prostate, muscles and joints (and probably a lot of other things); don't function properly without an optimal T/E ratio. Believe it or not. With that said, several other hormones are involved in our case.

 

[Mens Rea]

So finasteride upregulates androgen receptors, but I don't believe that they get downregulated when the DHT level increases again. It makes no sense. You don't see a downregulation in people who're abusing steroids which are much more anabolic and androgenic than both testosterone and DHT. Take a look at Halotestin.

I think their case is that, the upregualted receptors become damaged or even partially disabled more so than downregulated per se.

Can't comment on the steroid issues, but don't forget plenty of AAS users can screw up their systems too - probably for a variety of reasons.

What's perfect hormone levels? They don't have a clue, because it's all about ratios, and the optimal range is narrow, especially in relation to testosterone and estrogen. Your brain, penis, prostate, muscles and joints (and probably a lot of other things); don't function properly without an optimal T/E ratio. Believe it or not.

Noone know what an individual's "perfect" levels are but you can't oversee the "optimal T/E ratio" either. Why? Well.....watch a guy put on loads of weight...his T/E ratio will slowly change. Despite this, most people who put on weight won't notice appreciable effects to their sexual function. Some do, of course but rarely complete dysfunction.

The sides I have had from finasteride i would never have been able to get by putting on 10 stone. I know that is hard to prove but that's my opinion. My sexual drive and function reduced tenfold - i went from highly sexually charged to having symptoms of a hypogondal person. It's becoming increasingly clear to me that my problems lie much deeper than T/E ratios and that high estrogen is just a symptom of the problems i've inherited from finasteride. Something has to cause my high e2 to remain high after all....i've been off finasteride a year now it should never have risen naturally the way it has.

With that said, several other hormones are involved in our case

That's the reality. At least. The body is a complex mechanism and everyone works interdependantly. Adrenals, thyroids and the other sex hormones are all huge players in this.

 

[Ende]

Show me one case which someone has developed androgen resistance from use of medication. I've not found any. It seems like androgen resistance is something you're born with; and finasteride damaging androgen receptors...? No, it doesn't bind to the receptors, and people responds to Proviron. Even those who claims no steroids works, responded to Proviron - initially. It's all about balance. Men who're on TRT, and who never have used finasteride, sometimes experience a lot of the same symptoms. TRT makes them feel worse, and it's usually excessive estrogen which is the cause. For them, it's an easy fix, because they've not suppressed the DHT level like we have.

I've been very overweight, and despite of that, I had raging libido, and I always had morning erections, and spontaneous erections which I could chisel with. I think the problem with fat usually begins when your testosterone production begins to decrease naturally. That extra estrogen could mean a lot.

BB's usually screw themselves up with altered hormone levels; nandrolone is a common cause. My point, was that it doesn't make any sense that the wave of DHT which you get when you quit finasteride, should downregulate the androgen receptors because of "too much DHT". If the body worked this way, damn, those who used extremely androgenic steroids would destroy their bodies.

I believe that unbalanced sex hormones are the main cause, and all other hormones are altered as a consequence.

 

[Mens Rea]

Show me one case which someone has developed androgen resistance from use of medication. I've not found any. It seems like androgen resistance is something you're born with; and finasteride damaging androgen receptors...? No, it doesn't bind to the receptors, and people responds to Proviron. Even those who claims no steroids works, responded to Proviron - initially. It's all about balance. Men who're on TRT, and who never have used finasteride, sometimes experience a lot of the same symptoms. TRT makes them feel worse, and it's usually excessive estrogen which is the cause. For them, it's an easy fix, because they've not suppressed the DHT level like we have.

As Professor Bouloux told me, it's an extremely difficult theory to prove.

But PFS is a complex and in part, somewhat unique, condition. That is pretty clear from propeciahelp. It's uncanny.

You keep ignoring the fact that many guys on PH had tried high levels of TRT and have felt nothing. This is unprecedented.

Loads of guys have tried DHT cream and Proviron with limited effects too. It seems that provion effects often wear off for some reason (with PFS sufferers)....this is strange.

I've been very overweight, and despite of that, I had raging libido, and I always had morning erections, and spontaneous erections which I could chisel with. I think the problem with fat usually begins when your testosterone production begins to decrease naturally. That extra estrogen could mean a lot.

We all speak about our own experiences.

In my experience, i have out of range high Testosterone and out of range high DHT. Despite this I have these problems.

Professor Bouloux told me that if you have these 4 variables then you can atleast investigate the possibility of androgen resistence:


- Good LH levels (check)
- Good testosoterone and DHT levels (check)
- In range estrogen (hopefully, check....will see on next bloods)
- Hypongondal symptoms


Now, personally i think this is where thyroid and adrenals are important, i don't think im androgen resistent but I can see why certain individuals have conculded they might be.

BB's usually screw themselves up with altered hormone levels; nandrolone is a common cause. My point, was that it doesn't make any sense that the wave of DHT which you get when you quit finasteride, should downregulate the androgen receptors because of "too much DHT". If the body worked this way, damn, those who used extremely androgenic steroids would destroy their bodies.

I believe that unbalanced sex hormones are the main cause, and all other hormones are altered as a consequence.

[/quote][/quote]

Have a look at awor's story on PH. He's about 5 years ahead of us on all of this. He's tried everything you've tried already. It just didn't work for him.

There's other guys on PH with seemingly very good sex hormone levels. It just doesn't make sense for them to be having things like watery semen and penile atrophy when their hormones appear healthy. You could argue about ratios but some guys even have pre and post bloods which show nothing but yet they have the hypogondal problems. Dr Crisler he spoken about these guys himself. Perfect hormone levels but all the symptoms of PFS.....how the hell do you even treat this?

 

[Ende]

I'll shut my mouth forever, if those guys who claims they don't respond to any treatments, and complain about transparent prostate fluid and what not, rub Andractim on their scrotum for a week or two, and don't get white prostate fluid. I challenge everyone.

Bad ratios will give you a lot of problems, including symptoms of hypogonadism. Most doctors don't understand the significance of ratios - nor DHT, that's why they're unable to solve this problem.

As a note; testosterone gel is more appropriate than injections when attempting to treat our condition with TRT, as the gels increases the reductase activity a lot more than shots.

 

[Ende]

Btw mate, the reason I'm ignoring the fact that some people have tried steroids without any success at all, is because I've read a lot in HRT forums. Some of those people report the same problems.

 

[Mens Rea]

I'll shut my mouth forever, if those guys who claims they don't respond to any treatments, and complain about transparent prostate fluid and what not, rub Andractim on their scrotum for a week or two, and don't get white prostate fluid. I challenge everyone.
.

Speak to Oscar and Awor from PH....


Not to mention the fact that i have ridiculously high DHT levels and yet i have watery semen? It's nothing to do with DHT deficiency per se IMO is a prostrate issue and hormonal issue (potentially linked to FSH and Inhibin B).

Bad ratios will give you a lot of problems, including symptoms of hypogonadism. Most doctors don't understand the significance of ratios - nor DHT, that's why they're unable to solve this problem.

Bad ratios dont expain the guys who don't present with bad ratios. Maybe they're not "optimum" but a guy with seemingly normal levels shouldn't exhbit the symptoms we are speaking about.

It's easy to say but treating it is massively different. Some of the guys who have been at this longer than us believe the problem lies in 5ARII activity (hence why 3adiolG levels etc appear out of whack). Something like that isn't a hormonal problem, its much mroe deep rooted. A hormonal problem is only happening due to this 5ARII problem. Personally this doesn't seem to be the point for me but it does for the countless guys with 3-adiol-G levels lower than low.

Not to mention, this doesn't explain the guys who have pre and post tests.

 

[Mens Rea]

Btw mate, the reason I'm ignoring the fact that some people have tried steroids without any success at all, is because I've read a lot in HRT forums. Some of those people report the same problems.

Yeah, perhaps. I don't think propecia sufferers are all completely different (despite this being an apparent theme on PH) and i do feel most can mount a good recovery if they optimise T/E/DHT/PROGESTERONE in conjunction with adrenals and thyroids.

It does appear that there is something fundamental that has hit alot of the more extreme cases, though. Alot of these guys just appear "damaged" and unreceptive to alot of treatments. It's silly for you or I to tell them its a simple ratio issue when some of the top PFS doctors in the world have tried various approaches with little to no tangible results..


I'll say it again, Dr Crisler has spoken about some PFS guys with all these hypgondal symptoms despite completely healthy hormonal levels. You can't oversell "Ratios" that much. It they appear healthy (im talking about top level interpretation here - Dr Crisler is in this bracket) then they shouldn't be suffering from these problems.

Finasteride does more than inhbit DHT production it inhibits allapregnanlone converstion too for instance. It works from more than one angle, hence the myraid of problems associated.

 

[Ende]

I'll shut my mouth forever, if those guys who claims they don't respond to any treatments, and complain about transparent prostate fluid and what not, rub Andractim on their scrotum for a week or two, and don't get white prostate fluid. I challenge everyone.
.

Speak to Oscar and Awor from PH....


Not to mention the fact that i have ridiculously high DHT levels and yet i have watery semen? It's nothing to do with DHT deficiency per se IMO is a prostrate issue and hormonal issue (potentially linked to FSH and Inhibin B).

Forget about levels. If you try Andractim, and your prostate fluid turns white, DHT deficient is exactly what you are. It doesn't matter if your DHT level is above the normal range; your estrogen level is still too high in relation to the DHT level.

Bad ratios dont expain the guys who don't present with bad ratios. Maybe they're not "optimum" but a guy with seemingly normal levels shouldn't exhbit the symptoms we are speaking about.

Ask any doctor about ratios; he doesn't have a clue. There is no research done on ratios, only levels, so yes, symptoms of hypogonadism are normal despite of "normal" hormone levels.

It's easy to say but treating it is massively different. Some of the guys who have been at this longer than us believe the problem lies in 5ARII activity (hence why 3adiolG levels etc appear out of whack). Something like that isn't a hormonal problem, its much mroe deep rooted. A hormonal problem is only happening due to this 5ARII problem. Personally this doesn't seem to be the point for me but it does for the countless guys with 3-adiol-G levels lower than low.

If 5AR type 2 is the problem, HRT with DHT should work, and it does. I would like to see a clinical experiment on PFS and Proviron. It would reveal exactly what's happening, and how to solve the problem.

Not to mention, this doesn't explain the guys who have pre and post tests.

Who has baseline values of testosterone, DHT and estrogen?

 

[Ende]

Finasteride does more than inhbit DHT production it inhibits allapregnanlone converstion too for instance. It works from more than one angle, hence the myraid of problems associated.

Last time I checked, that neurohormone is converted by 5AR type 1, and not 2 - which finasteride inhibits. However, DHT affects your brain a lot, and I suggested that maybe those levels of neurohormones which Mew are talking about, decreases as a natural consequence to lowered DHT level, but I never got an answer.

 

[Ende]

Btw, I saw a study on Proscar a few days ago; and the free testosterone level decreased in all the subjects! I can't find it now, but it's interesting. SHBG has greater affinity for DHT, and testosterone obviously takes a hit when DHT is lowered by 70%. Merck don't mention anything about this.

 

[Mens Rea]

Btw, I saw a study on Proscar a few days ago; and the free testosterone level decreased in all the subjects! I can't find it now, but it's interesting. SHBG has greater affinity for DHT, and testosterone obviously takes a hit when DHT is lowered by 70%. Merck don't mention anything about this.

Of course they didn't.

 

[Mens Rea]

Forget about levels. If you try Andractim, and your prostate fluid turns white, DHT deficient is exactly what you are. It doesn't matter if your DHT level is above the normal range; your estrogen level is still too high in relation to the DHT level.

These guys have tired DHT cream, to no avail....

Ask any doctor about ratios; he doesn't have a clue. There is no research done on ratios, only levels, so yes, symptoms of hypogonadism are normal despite of "normal" hormone levels.

Agreed, but Shippen and Crisler etc are extremely clever guys. They operate on a "what works" basis.

Shippen is who gave you the concept of ratios so it'd be foolish to think Shippen doesn't look into this....

He deals with real life examples, not text books, man.

If 5AR type 2 is the problem, HRT with DHT should work, and it does. I would like to see a clinical experiment on PFS and Proviron. It would reveal exactly what's happening, and how to solve the problem.

Yeah but it doesn't. That's the point. Some of these guys simply seem damaged. The treatments that make perfect logical sense often makes them feel WORSE.

Almost never, will supplementing artifical hormones into the body, will help fix things. TRT is an exception in some ways but you know yourself its not ideal.

Pregnenolone, the mother of all sex hormones, is the only real exception in my opinion.

Not to mention, this doesn't explain the guys who have pre and post tests.

Who has baseline values of testosterone, DHT and estrogen?[/quote][/quote]

THere's a few on PH, i can't recall off hand but theres definately a few well documented cases.

 

[Ende]

Yes, some of my ideas comes from Dr. Shippen. He's aware of the significance of the T/E ratio, although Dr. Crisler claims that he has changed his view. However, I don't know if Dr. Shippen knows how important DHT is, and either way, like Dr. Crisler said - they're unable to experiment with DHT in U.S.

I don't think those guys have rubbed Andractim on their scrotum for a week or two, without seeing any change to their prostate fluid. Andractim is supposed to be rubbed in on the chest only, and to be fair, I used a lot for 1 1/2 month myself, without noticing any positive changes this way (except from removal of gynecomastia). Then I tried Proviron, and BAM. I felt normal, but quit in fear of hair loss, and began experimenting with Arimidex. Proviron isn't theory; I responded drastically to treatment, and so did monty and Joe.

 

[Mens Rea]

Yes, some of my ideas comes from Dr. Shippen. He's aware of the significance of the T/E ratio, although Dr. Crisler claims that he has changed his view. However, I don't know if Dr. Shippen knows how important DHT is, and either way, like Dr. Crisler said - they're unable to experiment with DHT in U.S.

I don't think those guys have rubbed Andractim on their scrotum for a week or two, without seeing any change to their prostate fluid. Andractim is supposed to be rubbed in on the chest only, and to be fair, I used a lot for 1 1/2 month myself, without noticing any positive changes this way (except from removal of gynecomastia). Then I tried Proviron, and BAM. I felt normal, but quit in fear of hair loss, and began experimenting with Arimidex. Proviron isn't theory; I responded drastically to treatment, and so did monty and Joe.

Yes, its an artificial boost that the body can't sustain, mate.

There are a few other guys that have tried proviron too, i've spoken to them extensively on PH via PM. Trust me on this, i'd did my due diligence, too. One guy in particular tried just about every approach possible from micro doses to huge doses. He tried cycling it.

This very guy is no recovering from a hugely specific diet. A really weird diet. I'll get you the info if you are interested?

Back to the proviron. Yeah, tHey all have had identical experiences. Good results for a short period then the effects disappear.

If i give my brother the proviron i have in my drawer theres no doubt he'll be horny as a goat and shooting huge wads too. It's what the drug does but it isnt a long term solution from what i gather.

 

[Ende]

That's were ratios comes in again. The point was that we're not dealing with damaged androgen receptors. Anyway, what do I know. I can't even stabilize my own condition, but it's now fluctuating between good and bad - according to adjustments in my treatment, and I'm convinced that I'm on the right track. We'll see.