I should of made more of the patterns in the blood tests. I’ll just try and shoe-horn them into this theory!
Low LH
I would suggest that deactivated hydroxy-testosterones are not in fact fully ‘deactivated’ but are only greatly weakened, therefore they are able to exert some negative feedback upon the hypothalimus/pituitary. In this study a deactivated hydroxy-testosterone was given to monkeys and led to ‘significant decrease in LH levels’ http://dx.doi.org/10.1016/0031-9384(76)90137-2. If this is true then deactivated testosterones should be able to fully compete for the androgen receptor, strengthening its role as an anti-androgen.
Low FSH
Likely as a result of a problem with Inhibin/Activin, seperate from the inputs that govern LH release. The reasons for this really do need to be looked into as it is such a common result for those that have been tested. This study, Testicular autoregulation: Possible role for 7-alpha-hydroxylated androgens ( see ncbi.nlm.nih.gov/pubmed/1943861), may support this theory, it states;
High TSH
Bit of a mystery. Not for everyone, but still common. Indicative of a thyroid problem, namely (subclinical) hypothyroidism. Most certainly a lot of the symptoms fit - especially reduced body temperature. (I have extreme intolerance to cold almost to the point of Reynaud’s.) Dont know how Fin could have caused this, prehaps an entirely seperate method of action like an auto-immune allergic reaction. Can anything else cause such low body temps??
This theory suggests that the ‘Post-Finasteride Syndrome’ is a problem with 5beta-reductase, not 5alpha-reductase. Finasteride also inhibits 5beta-reductase, which in turn controls the Pregnane X Receptor (PXR). Therefore the thrust of this theory is that there is a dysregulation/over-expression of the PXR.
Just an idea, but perhaps the usage of Fin has created an autoimmune reaction and inflammation in our livers. Remember Fin can cause ‘allergic’ reactions - why not in the part of the body most exposed to Fin? The body then begins to deal with this ‘inflammation’ once Fin use ends - when 5beta-reductase regenerates and PXR is invoked to deal with the inflammation.
This theory is becoming too loose. PXR may be involved but I sincerely doubt this is an autoimmune problem. Inflammatory markers which are a good measure of this are rarely raised in any of us. Aim to test for metabolites of testosterone to get your answer of how involved the liver is.
Too loose? i thought I was tying up all the loose ends!
I have now determined that one thing could cause all of our problems. An over-expressed Pregnane X Receptor (PXR). I think it would cause all the symptoms and all the blood test results.(see above)
The use of Finasteride inhibits 5beta-Reductase which deprives the PXR of its natural 5beta-pregnane ligands, thus reducing PXR expression and resulting in diminished CYP3A4 induction amongst other things. (see propeciahelp.com/forum/viewtopic.php?f=8&t=2703). When Fin usage ends 5beta-Reductase will regenerate, increasing PXR expression and therefore also increasing CYP3A4 expression and other functions etc…
Why should the PXR now be over-expressed? I dont know, thats what I’m now focusing on. Inflammation of the liver is just one idea at the moment. It wouldnt necessarily show up in standard blood tests - especially if its a subclinical variant of liver inflammation. Special diagnostic techniques may need to be employed. Anyway… I’ll run this past a Prof of Endocrinology tomorrow and make a fool of myself/see what he thinks.
Just been reading through my posts and realised that they make no sense . So I thought that I would summarise my idea.
My ‘theory’ is that it is Fin’s actions upon 5beta-reductase and not 5alpha-reductase which is the real cause of our problems. This theory presents something of a ‘third way’ between androgen insensitivity (due to epigenic changes to the AR) and some hormonal inbalance. Although it should be stated that the result of this theory is in fact a state of partial androgen insensitivity for some - because the body is producing a natural anti androgen.
Finasteride inhibits 5beta Reductase which controls the Preganane X Receptor’s (PXR) that regulate the hepatic enzyme CYP3A4 responsible for the metabolism of testosterone and xenobiotics (amongst others). As a result Fin can inhibit its own metabolism; resulting in high serum levels and side effects in the first place. – Clearly, for some, the longer Fin is used the greater chance there is for it to build up in serum and inhibit 5beta-reductase further, like a vicious circle, inhibiting its own metabolism more and more –
The thrust of this theory is that the Post-Finasteride Syndrome is now an over-expression of 5beta-reductase/PXR when finasteride usage ends. The opposite of what happens whilst it is being used.
This means there is now greater CYP3A4 phase 1 metabolism of testosterone. During phase 1 metabolism of testosterone its ‘deactivated/weakened’. This part of the metabolism is seperate to being made water soluble by phase 2 metabolism and excreted by the body. The main thrust of this theory is that the deactivated hydroxy-testosterone can act as a natural anti-androgen when there is a skewed hydroxyTest/Test ratio.
This theory is neat because the same process (over-active 5beta/PXR) would also create a number of coincidences:
Low Vitamin D levels (due to over-induction of CYP24 hepatic enzyme)
Raised Androstenedione (created from Test by CYP3A4 induction)
Lowered LH/FSH due to negative feedback on the pituatry by hydroxyTest (or its actions elsewhere in the genitals)
Symptoms of hypogonadism dispite normal Test levels
Also deactivated hydroxytest is an excellent substrate of 5aR!!! Therefore it can further inhibit this enzyme. The product of hydroxyTest + 5aR could even show up as DHT in normal blood tests - when in fact it would be a deactivated version of DHT! (prehaps dependant on the type of hormone assay performed) This would result in low 3aDiolG! {the fact DHT is still produced is problemetic for this theory however.}
(see sources above for evidence of all my proposals)
Yes, the word ‘inhibited’ I used above is just me being lazy.
‘Deactivated’ hydroxy-testosterone is an excellent substrate of 5aR - which is a good coincidence, it explains how a weak by-product can actually have powerful anti-androgenic activities as its primary side effect: which is what we see.
Therefore high levels of hydroxyTest competes for 5aR with normal testosterone. Now, we know that 5aR mRNA is actually increased by testosterone throughput. So the result is is either 5aR creating both normal DHT and deactivated-DHT (it has the capacity to do this) or hydroxyTest out competing normal Test for 5AR.
So the measurement of DHT (be it high or low) does not actually matter if there is a deactivated-DHT that may or may not be being included in the same result.
DHT can also be deactivated by the liver like testosterone. Andractim, etc, may also be further neutralised by the anti-androgen properties of all the deactivated hormones in serum.
Fin Inhibition of 5bR+PXR
Decreased CYP3A4 - leading to decreased xenobiotic (Fin) and testosterone metabolism.
Over-expression of 5bR+PXR (after stopping Fin)
Increased CYP3A4 - leading to increased testosterone metabolism/deactivation
Increased CYP24 - leading to low levels of Vitamin D
Actually if you look back in this thread you will see a quote from a message I recieved from a hormone testing lab. The message is an e-mail from Frank Nordt Jr Ph.D, the owner/director of Rhein Labs (I didnt actually contact him directly but he is the one that got back to me.)
He states that cross-reactivity between a hormone and its related metabolites is possible during testing, it depends wether the test is one based on mass spectrometry or an immunological reaction. Is it possible that the ones testing for high DHT actually have a closely related deactivated-DHT metabolite in their results?? Yes. Maybe. And its just one idea that should be mentioned. But as I stated in point (1) 5aR can actually increase its capacity so a deactivated version of DHT may be being produced that isnt detected at all in a normal test - which neutralises the effect of normal DHT. All of this is a better exlpanation and a more resonable reason for low 3aDiolG than something being wrong with the AR.
This theory is an explanation for the crash and full-blown hypogonadism, much better than it is an explanation for why things go wrong whilst using Fin that dont go back to normal. But, it is an explanation for how higher levels of Fin can build up which cause symptoms like using 5mg Proscar (or greater than 5mg!!).
An over-active PXR could be one thing that explains all of the symptoms men with PFS experience upon cessation of Fin (exept maybe the symptoms of simply getting a high dose whilst using it).
Noone knows why only a subset of men get problems (least of all me) or why why is this now happening. This all takes place in the endoplasmic reticulum of the liver and so may have something to do with a genetic polymorphism in this area (see endo.endojournals.org/cgi/content/abstract/151/12/5721 (although Ive had to fill in some of the details myself!).
The only tests I have found so far is a test for CYP450 3A4 induction by measurement of 6β-hydroxytestosterone/testosterone ratio or 6 beta-hydroxycortisol/cortisol ratio.
Determination of testosterone and 6β-hydroxytestosterone by gas chromatography http://dx.doi.org/10.1016/S0378-4347(99)00332-1
The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P4503A induction. ncbi.nlm.nih.gov/pubmed/2590599
A novel testosterone 6 beta-hydroxylase activity assay for the study of CYP3A-mediated metabolism, inhibition, and induction in vitro. ncbi.nlm.nih.gov/pubmed/12481849
Urinary 6beta-hydroxycortisol/17-hydroxycorticosteroids ratio as a measure of hepatic CYP3A4 capacity after enzyme induction. ncbi.nlm.nih.gov/pubmed/15298747
Urinary 6 beta-hydroxycortisol/cortisol ratios measured by high-performance liquid chromatography for use as a biomarker for the human cytochrome P-450 3A4. cebp.aacrjournals.org/content/1/7/567.abstract
Quantification of cortisol and 6 beta-hydroxycortisol in human urine by LC-MS/MS, and gender-specific evaluation of the metabolic ratio as biomarker of CYP3A activity ncbi.nlm.nih.gov/pubmed/19959402
This is a complete misconception. Just about every extreme is exhibited on this board.
My testosterone levels are top, top, level.
Source? I’ve seen a huge variation here. A lot of guys actually have quite low DHT levels.
Where’s your screening for this, exactly? Source please.
This one is a load of tripe. Apparently most men are deficient in vitamin D3 unless living in certain countries of strong climate. So it’s been hypothised that if there was a general testing of vitamin D that it would transpire that most post-fin’s vit D levels aren’t far from the average person.
Not to mention, mine’s SKY HIGH.
As would be expected from anything that has knocked testosterone/DHT/E2 etc out of whack.
See above. Also, many of these hormones are connected to the cortisol production line which you love to hear me speak of.
So it’s normal tesosterone now?
Firstly, most guys on here have messed up hormones. High E2 is a popular one.
Low testosterone is pretty prominent also. THAT is certainly one of the reasons PFS victims continue to have issues (hormone imbalance).
As for low levels of 3adiolG…downregulated DHT metabolism. You obviously don’t give any creedance to the cortisol hypothesis despite it being much more simple and supported by experts (Actual experts, not run of the mill endos that barely know how to treat a hypogondal person). You blasted me for pushing it but yet present a completely left field theory of your own based on several inaccurate foundations of your own.
I haven’t read it all. I think its unduly complex and its backward engineered to meet all the criteria that it sought from the outset (in terms of matching symtoms to theory). Also, it does appear to imply damnation despite the fact many people have been cured by several of the top PFS doctors by regular HPTA restart protocols which wouldn’t really work if this theory was to be correct.
THat’s not to suggest it doesn’t stumble over a few possibilities.
Kazman has mentinoed Inhibin B a few times, too. I might test this in my next round of bloods. Could explain a few things such as why post-fin users tend to find that Clomid doesn’t stimulate FSH like it should do (despite stimulating LH). I’m going to try this myself, though.
I read that IGF-1 stimulates inhibin B. Perhaps my high IGF-1 levels are involved here. My FSH is currently 1.6.
I don’t have high Androstenedione. I dont it’s overly common on here either?
[quote] High TSH
Bit of a mystery. Not for everyone, but still common. Indicative of a thyroid problem, namely (subclinical) hypothyroidism. Most certainly a lot of the symptoms fit - especially reduced body temperature. (I have extreme intolerance to cold almost to the point of Reynaud’s.) Dont know how Fin could have caused this, prehaps an entirely seperate method of action like an auto-immune allergic reaction. Can anything else cause such low body temps??[/quote
I honestly believe the stress of the thyroid function from the out of whack hormones is what causes thyroid problems. And therefore, also, the metablolism changes.
I compiled these urinary ratios from the testing members have posted and created a thread to showcase this -> viewtopic.php?f=4&t=4674
Maybe. But if you bothered to read the Vit D thread you will see men from hot climates also have low Vit D, including members from brazil and a man from spain with low Vit D and osteoarthritis. So not tripe - perhaps some hyperbole there Colin. see viewtopic.php?f=4&t=3420
Not that crap again
YES! Have you read anything on this website???
what are you talking about? what is DHT metabolism?!? Find me any academic source which discusses this - please.
No expert has ever, ever even mentioned anything similar.
Left field? That goes with the territory. Unfounded? Unlike you I have sourced everything before making any statements as should anyone proposing a theory (maybe not that left field since it is supported by academics to a certain extent -> endo.endojournals.org/cgi/content/abstract/151/12/5721)
gee thanks (actually this theory is overly long because it develops as i have new ideas to add.)
DUH! Not meeting the crieria would be pretty useless. no?
SOURCE?
well done.
I should also point out that the user Colin297 joined this website in 2007 promising never to use fin and then strangely starts posting again in 2010 after using fin viewtopic.php?f=4&t=4406&p=29138#p29138
Just for you personally im going to compile a list of sources. Only if you promise to actually read them, deal?
Don’t insult with the “im know more about endochrinology than you” bullshit, buddy. Where is that going to get anyone.
I’ve read ALL these threads already so no point pointing me towards them again. There’s a vitamin D thread of Dr Crisler’s forum too actually - unrelated to fin. The consensus seems to be that most people have low vit D unless supplemented… I think this whole vit D thing is a complete joke. At very best it is a sidenote.
Yet you say “not that crap again” when i have taken the time to link you to threads of people having success supplementing preg? When i have explained to you that Dr dr thierry hertoghe overcame his own PFS by supplementing TD progesterone? Why are you so quick to dismiss - may i add, agressively, yet propose your own theory much more complicated. Why not start with the basics and work from there?
I’ve got an excellent article about how critical it is for a male to balance his testosterone/estrogen/progesterone/DHT. You might want read it.
As for your DHT readings etc - you are jumping to WILD conclusions about what is normal and what isn’t. If you are going to base a well founded theory you’ll need to have better starting points. I understand you are in a disadvantaged position to hypothesise but atleast have the honesty to admit it.
Ultimately, you CLEARLY aren’t liaising in the right places when you’re asking me for a source whether Dr C, Dr Shippen et al have cured people. I’m telling you this from being told this myself, personally. You need to understand most people aren’t going to join a propeciahelp forum or post up all their bloods etc. It’s a pity they dont, but its the way it is. Basing your knowledge from this board alone is a bad starting point
Lastly, - and i want an answer for this right now - why do you continue refer to the fact i was on here reporting i ceased finasteride in 2007 only to come back 3 years later? Am i the only person to have had several attempts at this drug? I know for a fact i am NOT. What’s the big deal?
I am from hairlosstalk.com orginally and it’s so pro-fin over there i eventually decided to give it another bash given that the previous time all i had was a little ball ache from 6 months usage. If anything, knowing i could handle the drug was reasonable justification to “give it another try”. What are you being a complete cunt and using hingsight against me, exactly?
Hertoghe never had pffs lol, he took that to help with sides on the drug. There is a world of difference.
The guy you linked to who controlled his E2 with preg never took fin. Why didn’t you choose Electric Eye over there, he took fin, pesters chilln for help on a weekly basis and appears to be getting nowhere.
Point out the guys who Crisler or Shippen have helped back to normal with a HPTA restart.
Your tone is somewhat arrogant and patronising. You arrive here with minimal ‘PFS’, your sides are probably the same as about 25% of guys still on the drug, yet you think men here with far worse, life crushing symptoms just sit here and twiddle our thumbs. We have all been active on other forums, I was a member of Crisler’s forum long before you, if that even counts for anything.
Multitudes of men here have seen PFS docs, undertaken frequent and extensive bloods and undergone treatments and seen little to no improvement.
Crisler himself said, in a thread you were active on, that there is something ‘more ominous’ going on with PFS.
Ultimately because you have little sides, it is almost like an intrigiung little puzzle for you while it’s life or death stuff for most of the rest of us. I note you yourself have tried nothing despite berating us for this. And your e2 readings might be worthless anyway sinice they are not ultrasensitive, labs are meaningless for this on the NHS.
As for these theroies, we can’t solve this ourselves. We need the participation of scientists with experience and detailed knowledge of the androgen receptor, hormones etc. Hopefully the lawsuits will begin this process, as will other methods of increasing media awareness of this problem and finally getting it properly legitimised.
Ok, not “post” FS but “FS”. I mean, most of my sides appear to emanate from e2, too. So what is “finasteride syndrome” and what isn’t? Do you have to wait, untreated, until you are at a certain advanced point?
Anyway - my tone is just in response to Oscar’s who has been agressive to me from the word go. Not sure why, we’re both from the UK, we should be able to work together.
Crisler did say that - he admits he hasn’t quite pinned down the intregates of it yet but that is in relation to a BLANKET THEORY. Dr C works to fix YOU. And he claims to have did this for people. Why should i not believe him? I can’t point out the guys because im not Dr C or Dr Shippin.
I’m gettin assay readings actually.
Yes, pmgamer didn’t take fin, but i was talking about preg, in that context, to treat e2 issues. Why do you assume everything about fin - even high e2 - is completely unique to a point one cannot even begin to cross reference? I think it’s all about finding out what works for YOU. These blanket theories fall down at too many hurdles die to the variations seen on this board.
Androgen insensitivity, IMHO, isn’t a great th.eory. My main qualm with it is that it helps to justify “doing nothing” to fix the hormonal imbalances, thyroid problems etc that people need to iron out. At best (for the theory) there is mild AR acquired but considering some people “crash” and plummet overnight, whilst others slowly decline, i don’t see how it all would conceivably accomdate all these variations of PFS sufferer.
. So I thought that I would summarise my idea.
