clinicheck.com/cms/medicalservices/diagnostic-testsprofiles
Ask them.
I’ve had these done from them:
3 Adiol G (androstanediol glucuronide)
11b-OH-Etiocholanolone
5 alpha tetrahydrocortisol/Tetrahydrocortisol
Waiting for results.
If not look into things that act as substrates or inhibitors of the receptor - and see if any make a difference.
If the PXR is the cause it will be difficult to determine what is making it hyperactive since it has the largest binding site of any receptor (it is actually activated by many xenobiotics and endobiotics) and nothing actually seems to inhibit it directly. However it must be an endobiotic that wasnt there before that is now causing the receptor to be activated - we havent just ‘grown’ more 5alpha- and 5beta- reductase in the liver else the urinary 5a/5b profiles would surely show this. So when, in one of my more enlitened moments, i wrote;
There is actually another hormone that could cause these symptoms, something hitting the PXR, something that has possibly been overlooked, or not even investigated. Tetrahydrocortisol is a good place to start because we know thats changed - it may even be my ‘phantom DHT’ the product of hydroxytestosterone (from enhanced metabolism) + 5alphaReductase, that is now hitting the PXR (this would actually create a self-sustaining hormonal loop and be one possible reason the symptoms perpetuate).
But I cant see the point in speculating anymore without tests to back it up. The lab you linked to looks good - but doesnt do the test im after!
No one will listen to my crazy theories! 
But I may book an appointment; Or possibly a phone consultation with DrJacobs since we are legally allowed to import any medication (like testosterone) that we want as long as it is for our own private medical usage. (Sorry guys, this only applies to the UK as far as im aware)
If you look the tests I did some were not on the list either. You may need to ask your GP to write to ask them to do it - you are paying so they shouldn’t have a problem with taking a test. Most times GPs turn down things it is because it costs them and the NHS.
Ask them - be brief in the way you do it. Do not give a long reason why. They don’t care - you’re paying.
One reason its difficult to find a theory to fit all of the symptoms may be because not everyone has the same thing wrong with them. I should maybe start a new thread for this but i just want to mention it somewhere:
I believe that the side effects can be divided into the following 3 separate, but overlapping, categories;
[Size=4]A. Androgen Deprivation side effects[/size]
In my opinion, those only suffering from ED & low libido have the ‘standard’ side effects from androgen deprivation. It seems futile to attempt to exaggerate what could be causing their symptoms; it’s just the simplest answer. What exactly causes changes in sexual behaviour after using 5aR inhibitors - or any type of androgen deprivation for that matter - remains a mystery. Of course, it’s also a mystery why some are more sensitive than others.
[Size=4]B. ‘Brain Fog’ that starts on the drug and never goes away[/size]
Fin has many, many effects on the brain. If your main symptom (perhaps along with sexual dysfunction) is ‘brain fog’ or similar that never went away it would seem that one of those effects have caused lasting changes. As fin lowers dopamine that might be a good place to start looking for answers (perhaps permanently lowered dopamine or damage to a dopamine pathway and/or the limbic system).
[Size=4]C. A ‘crash’ after stopping that leads to symptoms of hypogonadism after suffering the effects of (1) and maybe (2) too.[/size]
How people get stuck with almost every symptom of low testosterone up to and including muscle loss after quitting fin is the biggest mystery of all. It appears to be an acquired form of androgen resistance.
There are a couple of different scenarios that possibly explain what’s happened;
’Liver theory’
Fin is inhibiting its own metabolism leading to higher incidences of side effects
When fin usage stops the same mechanism that was inhibited by fin is now hyperactive leading to a novel form of hypogonadism
’AR insensitivity theory’
fin lowers circulating androgens and ARs become hypersensitive
when fin usage ends androgens return, ARs undergo epigenetic changes and become insensitive to androgens.
So as you can see I now believe that there are three different categories of side effects that most people here are suffering from (I could also add a category of miscellaneous side effects). The main webpage of propeciahelp.com focuses on the experiences of someone suffering all three of these categories – but that simply is not the same for everyone with sides from fin. The only thing that links the symptoms is fin – but there may actually be different mechanisms behind the different symptoms. At least this is the way it appears to me from reading about the experiences of others.
I’d be interested in documentation to support this… do you have any? We know it inhibits allopregnanolone and THDOC and interferes with GABA-A receptors/GABAergic function in the brain, based on other published studies.
Just wondering if you’ve uncovered further evidence of other systems/pathways affected (ie, dopamine).
mindandmuscle.net/forum/index.php?showtopic=5950
This may be grasping for an answer a bit, but according to the studies cited here, GABA receptor activity can increase dopamine receptor sensitivity. Not a change in actual dopamine levels, but rather the effectiveness of dopamine.
Yes, theres evidence to support this. There are likely to be more studies, these are just the ones Ive read so far.
Adverse Side Effects of 5a-Reductase Inhibitors Therapy: Persistent Diminished Libido and Erectile Dysfunction and Depression in a Subset of Patients Traish et al
The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens Rouge-Pont et al
Antipsychotic-Like Properties of 5-α-Reductase Inhibitors Bortolato et al nature.com/npp/journal/v33/n13/full/npp200839a.html
It appears fin also has indirect effects on dopamine. Its not a very nice to think this drug may have ‘destroyed’ the dopamine in our brains - but perhaps the mental symptoms match this better than anything else? Two scientists I have spoken consider a problem like this to be the cause (and ignored physical changes completely!). Dopamine is relatively well studied however, and I know of drugs that can cause large and permanent rises in dopamine receptors.
Something else - if 3adiolG has got anything to do with it (big IF) there may be an alternative/overcompensating pathway for the DHT metabolites within the body. I say this because DHT must end up in some other form before it is used and removed from the body other than 3alpha-Androstanediol Glucuronide. (see viewtopic.php?f=4&t=518)
The alternatives include;
DHT Glucuronide
DHT Sulfate
3beta-Androstanediol
Androstanedione
Androsterone
Androsterone Glucuronide
3alpha-Androstanediol Sulfate
According to this theory thread the increased metbolism via PXR/CYP3A4 will result in higher sulfotransferase expression and more sulfanated hormones (“sulfonated hormones often fail to bind to and activate their cognate receptors and thus lose their hormonal activities”).
Hello. I recently posted a refined version of my theory in the finasteride thread of Dr Crisler’s forum. As of yet he hasnt given any feedback (he may never give any) but I will share it here too.
The short version: The liver is still working as if we have finasteride in our system. Instead of metabolizing xenobiotics it is now metabolizing (deactivating) sex hormones.
This is the only way I have found in the literature that our (my) symptoms can be created - enhanced metabolism. Yes, it MUST be the deactivation of ALL sex hormones and not just androgen insensitivity else we would all show strong estrogenic dominance like side effects, which isnt true.
Of course this theory doesnt explain why (1) side effects happen on the drug that never go away or (2) why enhanced metabolism is now occuring off the drug.
In answer to those two points I would give this even more speculative answer: In the 5a/5b metabolite sticky thread there is a definite alteration to the ratios and amounts of 5a & 5b reduced metabolites. The most stricking example is actually the metabolites of cortisol. If fin has altered these the liver may ‘read’ this as the presence of xenobiotics therefore creating enhanced metabolism to ‘flush’ it out. This could start on the drug. Why these metabolites have changed, i dont know; Presumably it is self sustaining, or caused by inflammation or probably something else.
I gave grapefruit juice a go and felt different on it. Not better just different. Probably as it increases estrogens in blood as it increases its half life. But doesn’t it also increase testosterones half life? I know if testosterone estrogen balance is out - bad things happen especially as our systems are so sensitive now. On bright side estrogens are good for bones.
Could I ask you guys to try grapefruit juice for a week one bottle a day and let me know how it makes you feel?
Great theory Oscar. Has the possibility of permanent out of control steroid metabolism been mentioned to any of the PFS doctors?
Yeah, I tried it but it didnt really do much - plus the stuff tastes disgusting.
It is a good theory. Actually its a great theory. In fact this theory has been discussed since this website was started (and possibly before): anabolicminds.com/forum/male-anti-aging/75428-liver-cyp3a4-enzymes.html. It was only very recently, with discovery of this paper Pregnane X receptor as a therapeutic target to inhibit androgen activity http://www.ncbi.nlm.nih.gov/pubmed/20962047 that I was fully able to put it all together.
I do not know if anyone has mentioned this to any of the PFS doctors. I have emailed the idea to a few of them and posted this theory on Dr Crislers website (which he frequents almost every day). I have recieved no reply. It doesnt help that this problem (if indeed it is happening as described) isnt known to have happened before, and I cant think of any reason why it should be happening.
A test for this is commercially available questdiagnostics.com/hcp/files/endo2002.pdf.
I crashed upon drinking heavily on my birthday 2010. Every single crash I’ve had after that has been alcohol related. Every time I drink it set me back. I think this theory has a lot of weight. Also, my rhine labs testing shows above range testosterone in the urine which means its being excreted like mad. I one thing that I’m miffed at how how the low DHT metabolite fits into this thing as we all seem to have low 5a reductase activity.
Can someone PLEASE do this test?
We need answers.
Moved this post from “Post your 11b-OH-Etiocholanolone & 5a/5b urine metabolite ratio results”
I wanted to share these studies with the forum.
http://toxsci.oxfordjournals.org/content/92/1/51.full
http://www.ncbi.nlm.nih.gov/pubmed/17962516
“If” over-expression of PXR is involved in our problem, these articles may provide a link to the similarities in symptoms between finasteride sufferers and accutane sufferers. They state that retinoic acid (accutane) can cause significantly increased expression of pregnane X receptors and that the up-regulation of PXR can actually cause resistance to the drug.
I used to use an aftershave that had ‘retinol’ in it while I was on fin. I wonder if this had an impact? Has anyone else used skin products that contained retinol? To the point about the second study regarding retinol.
I tried grapefruit juice the past three days. I did a high quality not from concentrate one and drank 3-4 8oz glasses per day for the past three days. Long story short, I feel like shit. I think it has raised my estrogen ratio. I had to piss a ton last night, my stomach has increased fat, nipples feel a bit more swollen. Muscles really soft. ED is worse. I don’t know if I should stay with this or abandon ship. I don’t know if three days is long enough to make any judgement. I can feel things moving around in my mid section and hear it growling. Some crazy reactions going on down there. Maybe an estrogen blocker is required.
There has to be something too this.
I highly doubt this effected you in any significant way unless you were eating it. You would have just been applying a low dose to your skin. I have yet to hear of anyone who used a topical application of a retinoid complain of pfs-like side effects, only people who have actually ingested medications similar to retinol have these horrible side effects.
That doesnt sound good. Almost the exact opposite of what should happen.
I really thought this theory had a lot going for it. In fact this idea, increased sex steroid metabolism, is the last way known to science that testosterone can stop working.
Pregnane X Receptor as a Therapeutic Target to Inhibit Androgen Activity endo.endojournals.org/cgi/content/abstract/151/12/5721
The research from this paper tells us that hypogonadism can in fact exist in three forms:
A problem with the production of testosterone, leading to low serum levels.
Interference; from other hormones (estrogens) or drugs like flutamide, or binding to SHBG.
and now a new third catagory,
( 4. I would suppose it could also be due to a defect at the androgen receptor.)
This is how low 3aDiolG fits in with this metabolism idea:
3aHSD is the next step after 5aR that turns DHT into 3aDiol. It occurs before the androgen receptor, and is thought to control the access of DHT to the androgen receptor. 3aDiol is in fact the deactivated form of DHT.
The steps in the production of of 3alpha Androstanediol Glucurinide (3adiolG) goes something like this - Testosterone > 5aR > DHT > 3aHSD > 3aDiol > Glucuronyltransferase > 3aDiolG
Reasons I can imagine for low 3aDiolG:
(1) If there is less 5aR then there will be less 3aDiolG, since there is less intracellular DHT to deactivate.
(2) If there is less 3aHSD there will be less 3aDiolG.
However in that scenario less DHT will be deactivated and so surely more DHT will be available to activate the androgen receptor. I suppose only if there is less androgen receptors and less 3aHSD will we have the symptoms and the blood test results (something along the lines of Awor’s theory?).
(3) Other enzymes are preventing the binding of DHT to the androgen receptor and the conversion of DHT to 3adiolG.
I have discovered that if the normal metabolism of sex hormones is increased then DHT will often fail to bind to the androgen receptor. This is due to increased conjugation by Sulfotransferase. There will also be less 3aDiolG due to a bias towards 3alpha Androstanediol Sulfate, or due to less DHT being deactivated by 3aHSD due to less DHT activating the androgen receptor.
(However, if the Androgen receptor is ‘broken’ it my also be the case that less 3aHSD is invoked to deactivate DHT)
