I’ve posted this before but 5 alpha reductase activity is testable through genital skin fibroblast testing.
Kazman, From the chinese paper. (ps All of those results quoted are RhineLabs 24hr urine tests.)
In the pairs listed above the 5alpha metabolite is first and the second is the 5beta, same as the chinese paper.(see quote above and pic)
I dont see the paper mention lower 20%. It does mention unambigious and extremely low levels of 5alpha reduced metabolites in 5ar2 deficiency. (Although the THB and THF ratios are low.)
The (corrected) results I have posted above therefore reveal a strong ratio in favour of 5alpha metabolites. This cannot be a 5aR deficiency. The only exeption seems to be Tetrahydrocortisol. Might be wrong, it is late 
Ranges (urine/24hr, 5-alpha/5-beta);
Androsterone (2.10-6.30)/ Etiocholanolone (1.90-5.70) = A/ET
11-OH-Androsterone (1.20-2.60)/ 11b-OH-Etiocholanolone (0.05-2.10) = OHA/OHET
5a-Tetrahydrocortisol (1.00-2.60)/Tetrahydrocortisol (1.20-3.30) = 5aTHF/THF
[b]Penguin:
A 4.18/ ET 3.13
OHA 1.65/ OHET 0.20
5aTHF 1.45/ THF 2.12
Jairus: (hypogondal low T levels)
A 4.76/ ET 5.50
OHA 1.63/ OHET 0.87
5aTHF 1.06/ THF 2.83[/b]
Just a thought…
Characteristics of 5α-reductase-2 deficiency:
(1) normal to elevated levels of plasma testosterone;
(2) decreased levels of plasma DHT;
(3) an increased testosterone to DHT ratio (or following hCG stimulation);
(4) decreased conversion of testosterone to DHT;
(5) reduced 5α-reductase activity in genital tissue and cultured fibroblasts;
(6) normal metabolic clearance rates of testosterone and DHT;
(7) decreased production of urinary 5α-reduced androgen metabolites with increased 5β/5α urinary metabolite ratios; hkmj.org/article_pdfs/hkm0904p130.pdf
(8) decreased plasma and urinary 3α-androstanediol glucuronide, a major metabolite of DHT; ncbi.nlm.nih.gov/pubmed/2770532
(9) a global defect in steroid 5α-reduction as demonstrated by decreased urinary 5α-reduced metabolites of both C21 steroids and C19 steroids other than testosterone (e.g. cortisol, corticosterone, 11β-hydroxy-androstenedione, and androstenedione). ncbi.nlm.nih.gov/pubmed/4028464
(10) Increased plasma levels of LH, an increased LH pulse amplitude with normal LH frequency. jcem.endojournals.org/cgi/reprint/78/4/916.pdf
The strongest marker for 5aR Type 2 in the liver is low 5a-THF/THF ratio (see jcem.endojournals.org/cgi/content/abstract/54/5/931) this is what the blood levels reveal here . Results will show low 3α-androstanediol glucuronide as well, a peripheral marker of 5aR type 2 activity. This is point (8) and partially points (7) and (9) above. This cannot be a 5aR Type 2 deficiency but could it be a ‘damaged’ Type 2 enzyme due its repression?
Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase. pnas.org/content/88/18/8044.full.pdf+html
Conclusion…
5a-Reductase mRNA has been reduced and has not recovered after stopping fin. OR. As the paper above suggests, 5a-Reductase may be invoked by DHT interacting with the androgen receptor, if this does not happen, there will be continually reduced 5aR. OR. The 5a-Tetrahydrocortisol ratio is low for some other reason. (Like something interfering with 5aR, see here for one theory viewtopic.php?f=27&t=4260&start=20)
Oscar, the 5a THF/5b THF ratio (or in inverted form with appropriate range) is the one Crisler and many other doctors cite as being the most sensitive and reliable from a diagnostic standpoint. The Chinese paper clearly indicates that one of the other ratios is not sensitive to the condition (don’t feel like looking up that portion of the paper at the moment).
Look, if half our urinary metabolite ratios are low it must mean something, e.g. gene expression at a minimum, possible damage to one or more of the 19 genes that encode SRD5AR2 at the maximum. The men being studied were born with ambiguous genitilia via mutation of the genes at birth/due to inbreeding etc. Therefore they are worse, as exemplified by very low DHT levels (mine and many others are normal or at least mid range). I can not agree with your conclusion just because some of us have 5a metabolites that are not “unambiguously low” via serum testing doesn’t mean the urine ratios aren’t a marker of something wrong. I have further information here I can PM you if you would like.
Mariobros, ever try to get an academic research lab to actually run the genital skin fibroblast testing? I mean one that knows how - they aren’t interested outside of doing it within a research grant setting due to “human subject” regulations/red tape etc. This has been my experience thus far, if anyone has found a lab willing to do this for a reasonable amount of money please let me know.
Ok, sorry man i didn’t realise.
On a side note, i think that a lab study is something that we should all be focused on at the moment, particularly with Dr. Irwig’s study about to be published. I sent a message to Mew today to see if admin could setup a way for people to donate through the site with Paypal or bank deposit, into a third party managed account. i know this has all been suggested before and it would be no small project but it would be a pro-active step forward.
Comparing the ratio of the below two hormones is suppose to give a good indication of 5-AR-2. Since there has been some debate as to if 3adiolg is the best marker or if its a marker for androgen receptor activity.
24hr Rheins urine analysis provides measurements of THF (tetrahydrocortisol) and 5a-THF (allo-tetrahydrocortisol), and the ratio of 5a-THF to THF ( ie: 5a-THF / THF ) follows the 5alpha reductase activity, ie:
high ( 5a-THF / THF > 1.3 ) shows high 5 alpha reductase activity (above 90 percentile)
mid ( 5a-THF / THF = 0.8 ) shows average 5 alpha reductase activity
low ( 5a-THF / THF < 0.6) shows low 5 alpha reductase activity (below 10 percentile)
My readings are as follows:
THF 2712 ug/24hr range: 942-2800 ug/24hr
5a THF 714 ug/24hr range: 796-2456 ug/24hr
Therefore: 5a THF/THF= 714/2712
Ratio= .263
Makes sense. I’m a mess.
Umm this than appears to be raw proof that low 5-AR-2 is the cause of our problems.
Why is 5-AR-2 still being surpressed after we have come off thou?
And more importantly what can fix it? I think cyclosporin a might be our hope.
I was a little confused about what exactly this thread was asking for but…
My results from Rhein Labs 24hr urinary profile:
Androsterone= 6042 (H)
11b OH Androsterone= 744
Etiocholanolone= 8004 (H)
11b OH Etiocholanolone= 285
THB= 194
5a-THB=318
THF= 1857
5a-THF= 787 (L)
Ranges provided by kazman
[b]A/Ae= 0.75 range 0.7-3.0 (Low end of normal)[/b]
1 1OHA/11OHET= 2.6 could not find range
5a THB/THB= 1.6 range 0.8-3.5
5a THF/THF= 0.42 range 0.5-2.5 (LOW)
And again, a low ratio this appears to be the culprit… no more debating over androgen insensitivity, neurosteroids or cortisol management…
All the thyroid and cortisol issues must stem from this because it is the main action of finasteride to disrupt 5-alpha reductase type 2, and what do we all have in common? we all used some form of a 5-AR-2 inhibitor.
I’ve thought it was this for sometime now, based on the combination of side effects I experienced and the role of 5-AR-2 in the body.
Now why did our bodies down regulate 5-AR-2 after coming off finasteride? Could it be some immune reaction with the CNS? Perhaps that is why drugs like morphine, and GHB and heroine have been shown to have some effect. They act directly on the CNS.
Argument for 5aR being downregulated:
1.Low 3aDiolG
2.THF/5a-THF ratio shows low 5alpha activity (or high 5beta activity!)
Arguments against:
1.Normal DHT
2.All other 5alpha metabolites and ratios normal
(Of course these results against are less important when deciding 5aR activity, but the hormone tests would be very apparant in someone who is using Propecia for example.)
3.Symptoms unconnected to 5aR - muscle loss, bone problems, low body temperature, (anhedonia?) - do occur.
4.Why do people, like you and me, get worse after stopping? As you point out, thats a problem, because you have to invent some new other reason for 5aR to become downregulated, not connected to the damage finasteride should have caused. This surely points away from 5aR downregulation.
5.Our symptoms arent found in people who are currently using finasteride (or even dutasteride) to inhibit 5aR.
So the theory for Propecia destroying 5aR is compelling, but there are clear unavoidable problems with it. (ps Im not a cellular biologist).
(Personally I dont agree with it at the moment, Im a bit stuck on my current idea that the liver is deactivating our sex hormones, 3aDiolG is just a marker for DHT activity and high THF could be a marker for a liver problem, or something.)
All of my primary sex hormones are in good ranges test is over 800 for example.
My 3adiolg is below range low.
My cortisol is well above range.
I’m getting my thyroid hormones run and should have the results maybe by early next week.
My DHT is in normal range but flucuates constantly. whereas my testosterone is consistantly over 800.
If its not 5AR2 than it must be an another enzyme, perhaps something we have yet to identify.
Personally I think it is 5ar2, and we didn’t recover after coming off because our bodies had a autoimmune response to the flush of 5ar2 activity and thus downregulated it in the CNS.
What about people who developed sides on the drug, never had a brief recovery and have yet to experiance any sort of improvement? Do your theories incorperate this type of victim, if so please explain.
… So maybe low 3aDiolG isnt necessarily due to low 5aR activity? The fact that DHT is normal (or in Mew’s case and a few others out of range high) it simply must still be working. Ill just take a moment to explore this idea.
The steps in the production of of 3alpha Androstanediol Glucurinide (3adiolG) goes something like this - Testosterone > 5aR > DHT > 3aHSD > 3aDiol > Glucuronyltransferase > 3aDiolG
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.
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.
Oscar, you need to separate out 5 alpha reductase types 1, 2 and 3. Adiol-G is a marker for 5AR2 activity only (as well as peripheral androgen action, but that is a receptor effect and not something that produces DHT). The attraction of urinary metabolite ratios is that the three being discussed are markers for 5AR2 and nothing else.
In some 5AR1 is suppressed as well, leading to low DHT levels. In some others I suspect 5AR2 is highly depressed, so the 5AR1 pathway goes into hyperdrive making lots of DHT to try to compensate, but that still odes not provide 5AR2 for the prostate, brain, liver etc.
Perhaps we should split this thread into a technical discussion, and a separate place to collate the metabolite ratios and serum 11b-oH Etiocholanolone levels. In the meantime lets move technical discussions elsewhere.
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I believe a correct reading of this thread viewtopic.php?t=761 shows that 3aDiolG is produced by 5aR types 1 & 2 but is mostly from type 2. Both types of 5aR also produce DHT, at a ration of 30%/70%.
The urinary markers show the activity of both 5aR types 1 & 2. (Otherwise the type 2 deficient people would have no 5alpha reduced metabolites in their urine!)
Thats the obvious conclusion. But, both 5aR types 1 & 2 are present in the brain and liver. If 5aR1 was ‘compensating’ this would be revealed in the urinary metabolites too. It doesnt show this. Also, levels of DHT do not correlate to severity of symptoms. Also, this doesnt match why people get worse after stopping, or the non-5aR related symptoms.
Or keep it all in one place, since this is an important set of results but not many people seem interested or realise the relevance of this thread.
Is anyone able to determine how cortisol can have two sets of 5a/5b reduced metabolites? These are also the metabolites that come back showing an unusual pattern.