PROPECIAHELP: Persistent Finasteride Propecia Proscar side effects info & discussion forum

Forum for men with PERSISTENT sexual, mental & physical side effects which CONTINUE DESPITE QUITTING Finasteride (Propecia, Proscar), a 5AR inhibitor drug for hair loss, prostate enlargement & prostate cancer.
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PostPosted: Tue Aug 14, 2007 1:07 am 
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According to http://www.emedicine.com/med/topic3489.htm , it is possible to test for 5AR activity via blood/urine test:

-------------
"In the pilosebaceous unit and peripheral tissues, DHT is metabolized further to 3a-androstanediol.

3a-androstanediol glucuronide, the final metabolite, can be measured in the plasma and indicates the level of activity of target tissue conversion of testosterone and androstenedione to DHT.

The relative activity of the 5a-reductase enzymes can be determined by measuring 3a-androstanediol glucuronide in either urine or blood."

--------------

3a-androstanediol glucuronide is also known as "Adiol-G", and should be ordered as it is a metabolite of DHT and thus a more accurate representation of 5AR-II activity .

The following labs in the USA CAN TEST FOR 3a-diol G, here are the test #s:

ARUP LABS:
http://www.aruplab.com/guides/ug/tests/ ... ronide.jsp

http://www.aruplab.com/guides/ug/tests/0078001.jsp

QUEST DIAGNOSTICS:
http://www.questdiagnostics.com/hcp/tes ... abCode=SJC

------------
More info on Adiol-G and 5AR: http://jcem.endojournals.org/cgi/reprint/76/4/977.pdf

Looks like the liver playes a big role, responsible for 90% of circulating Adiol-G. There is also a great diagram of 5AR metabolic pathways on page 2, with additional hormones one could test for.

Also note:

"Lobo et al. have demonstrated Adiol G production in genital skin and have shown that serum Adiol G levels correlate with skin 5a-reductase activity."


Last edited by Mew on Mon Sep 14, 2009 7:24 pm, edited 5 times in total.

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PostPosted: Fri Nov 16, 2007 1:16 am 
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Good little study about how Finasteride impacts 5AR activity, and how/what they test to evaluate 5AR activity. Includes graphs.

Show this to a doc next time they claim you can't test for 5AR activity.

-----------

Laboratory Monitoring of Androgenic Activity in Benign Prostate Hypertrophy Treated with a 5a-Reductase Inhibitor:
http://www.clinchem.org/cgi/reprint/38/7/1304

"androsterone/etiocholanolone (A/B) ratio in urine as a measure of 5a-reductase activity."

This measure was used previously by Zumoff et al. (5) to show variations in metabolism of testosterone according to age and sex: the mean A/E ratio for men ages 14-45 years was -1.5 but fell to 1.0 or even slightly lower in elderly men (ages 69-87 years).

Because the analytical result is expressed as a ratio, absolute values are not required and random sampling of urine is sufficient for assessing the ratio of 5a-/5b-reductase activity.



-------------

Here is another example of how to measure 5AR activity:

Plasma androsterone/epiandrosterone sulfates as markers of 5α-reductase activity: Effect of finasteride in normal men

http://www.sciencedirect.com/science?_o ... 08b8a30973

Plasma androsterone/epiandrosterone sulfates, dehydroepiandrosterone sulfate, dihydrotestosterone, testosterone, androstenedione, and cortisol were measured in three normal adult men before and following finasteride administration (5 mg/day).

Plasma androsterone/epiandrosterone sulfates and dihydrotestosterone declined in parallel to 50% of basal levels with little change in either dehydroepiandrosterone sulfate, cortisol, or androstenedione.

The results suggest that the direct measurement of plasma androsterone/epiandrosterone sulfates by enzyme-linked immunosorbent assay provide similar information to plasma dihydrotestosterone and therefore provide a simple alternative for the assessment of 5α-reductase activity.


Last edited by Mew on Fri Dec 21, 2007 9:31 pm, edited 2 times in total.

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PostPosted: Fri Nov 16, 2007 3:37 pm 
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Interesting...

I'll note from my own urine analysis that my androsterone was 5803 and my etiocholanolone was 2245, yielding a whopping ratio of 2.58...I'm unsure of the method Dr. Crisler used when he evaluated this but he did tell me that 5AR activity was "fine".

This might explains why although my testosterone is low my DHT appears to be normal.


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PostPosted: Tue Jan 01, 2008 11:18 pm 
Do you have any contact to Dr. Crisler.

I would also like to know If someone from Europe is present on this forum and knows where is it possible to do an Adiol-G and DHT test.

I live in a central Europe so I can travel to most places.


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PostPosted: Thu Feb 14, 2008 11:05 pm 
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You can check DHT in France, I live in Paris and there is no problem with that at all.


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PostPosted: Wed Feb 20, 2008 7:20 am 
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It has been suggested around here a few times that testing for DHT via bloodtest may not necessarily be the most reliable indicator of true 5AR-II activity.

The attached screenshots may provide some evidence as to why, from http://books.google.com/books?hl=en&lr= ... gsZAvVuuWM

and http://books.google.ca/books?id=hurRyWj ... w#PPA61,M1


The question is, how MUCH does 5ARI and II contribute to serum DHT, respectively? That question can likely be answered by looking at the effects of a dual inhibitor of 5AR I & II (Dutasteride) vs Finasteride (5AR-II only).

http://www.pubmedcentral.nih.gov/articl ... gure&id=F2


As you can see in the link above, 5AR-II contributes approximately 70% of serum DHT, while 5AR-I likely makes up the remaining 25-30%.

-----------

Thus, in addition to testing for Adiol-G, other methods to test ONLY for 5AR-II enzyme function/activity would involve:

- Genetic PCR analysis to check for 5AR2 enzyme mutation

- Genital Skin fibroblast culture/assay, since 5AR2 is abundant in genital foreskin and thus DHT binds to androgen receptors in the foreskin to exert it's function: http://www.blackwell-synergy.com/doi/ab ... alCode=bjd

"Fibroblast cultures have also been shown to be an excellent model for the screening of compounds which might block the expression of androgen action by competing for the androgen receptors. Cultured skin fibroblasts are a valuable model for the study of androgen and antiandrogen action in human skin."


Attachments:
dht-5ar1-2.jpg
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Last edited by Mew on Tue May 20, 2008 11:19 pm, edited 2 times in total.
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PostPosted: Thu May 08, 2008 6:28 am 
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According to the below, SERUM (blood) based DHT tests are not necessarily an accurate representation of true 5AR-II activity (at least in the prostate).

**** Testing for ADIOL-G is.
****

Although this mentions intraprostatic DHT, I would assume this would likely apply for circulating DHT outside of the prostate as well.
So on future bloodtests request ADIOL-G, in addition to DHT.

---------------

Association between Two Polymorphisms in the SRD5A2 Gene and Serum Androgen Concentrations in British Men

http://cebp.aacrjournals.org/cgi/content/full/12/6/578

"It is well established that the steroid 5 -reductase type II enzyme, which irreversibly converts testosterone to its more potent metabolite DHT3 in prostatic cells, is required for the normal growth and development of the prostate gland (1) .

A meta-analysis of prospective studies suggests that the serum concentration of A-diol-g, a serum marker of the abundance of 5 -reductase type II and intraprostatic DHT, is slightly higher in men who subsequently develop prostate cancer compared with healthy individuals (2) .

The circulating A-diol-g concentration is believed to be a more accurate serum marker of 5 -reductase type II than serum DHT itself, because A-diol-g is the direct metabolite of DHT formed in the prostate gland. However, circulating DHT is largely derived from 5 -reductase type I activity in the skin and is therefore not an accurate marker of intraprostatic 5 -reductase type II activity. "


Last edited by Mew on Tue May 20, 2008 11:21 pm, edited 3 times in total.

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PostPosted: Tue May 20, 2008 11:02 pm 
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Quote:
Although this mentions intraprostatic DHT, I would assume this would likely apply for circulating DHT outside of the prostate as well.


BELOW: Further confirmation of the above (that 3alpha-diol G reflects 5ARII activity in both serum and tissue).


From http://epirev.oxfordjournals.org/cgi/reprint/23/1/42

"Dihydrotestosterone levels in tissue are several times
higher than the levels of testosterone, but serum levels of
dihydrotestosterone are only 10 percent of the serum levels
of testosterone because most dihydrotestosterone is produced
in tissue
. In epidemiologic studies, serum levels of
3a-diol G are commonly used as an indirect measure of 5areductase
enzymatic activity,
since it is not feasible to measure
tissue levels of testosterone and dihydrotestosterone in
cases and healthy subjects.

The current belief is that serum
levels of 3a-diol G reflect enzyme activities of both steroid
5a-reductase types 1 and 2.


However, in studies of men
treated with finasteride, a 5a-reductase type 2 inhibitor,
serum levels of 3a-diol G decrease concomitantly with
finasteride treatment, suggesting that 3a-diol G levels predominantly
reflect the activity of the type 2 enzyme
(10)."


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PostPosted: Thu Dec 18, 2008 9:01 pm 
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Mew, I noticed that Dr Crisler mentions on his board that "the best biomarker for 5-AR activity is THF/5-a-THF." I don't know anything about these, but the two of them are on my Rhein Labs form, so they're getting tested. Know anything about these and how they compare to Adiol-G?


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PostPosted: Sat Jun 06, 2009 8:01 pm 
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In addition to the above info, it would appear the most reliable way to get an accurate reading of 5AR2/DHT activity post-Finasteride would be via genital skin fibroblast culture, based on the attached screenshot.


Attachments:
dht-tissues.gif
dht-tissues.gif [ 13.05 KiB | Viewed 34077 times ]
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PostPosted: Fri Jun 26, 2009 11:05 pm 
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Attached -- a recent 2009 paper (Diagnosis of 5alpha-reductase 2 deficiency.pdf) on testing for 5AR2 deficiency via measuring 5A/5B metabolites & ratios via 24 Urine Panel (ie, Rhein Labs -- http://www.rheinlabs.com/hp.html )

... and gene mutations (ie http://www.genetests.org/servlet/access ... how_flag=c )


Print this out... bring to docs. Discussion section sums it all up nicely.

---------

One other study also attached (Intramuscular administration of 5a-dihydrotestosterone heptanoate -- changes in urinary hormone profile), with other ratios one can test for.


Attachments:
Intramuscular administration of 5a-dihydrotestosterone heptanoate -- changes in urinary hormone profile.pdf [198.42 KiB]
Downloaded 957 times
Diagnosis of 5alpha-reductase 2 deficiency.pdf [358.07 KiB]
Downloaded 1200 times


Last edited by Mew on Tue Sep 15, 2009 5:33 am, edited 2 times in total.
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PostPosted: Sat Jun 27, 2009 11:41 am 
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.


Last edited by solonjk on Sun Jul 10, 2011 3:41 pm, edited 1 time in total.

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PostPosted: Mon Sep 14, 2009 9:07 pm 
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I have found an article that states the following:

http://www.nature.com/jid/journal/v119/ ... 1659a.html

"Clinically, it is still controversial if serum levels of 3alpha-Adiol conjugates (3alpha-Adiol glucuronide or 3alpha-Adiol sulfate) serve as reliable indicator for cutaneous 5alpha-DHT formation (see later,Lookingbillet al, 1988a;Horton, 1992;Vogt et al, 1992), or are just a marker of adrenal steroid production and metabolism"

This could support the fact that the low readings of 3 adiol G are corresponding to adrenal fatigue that we might be experiencing post finasteride.

Also, in this paper they state that 5AR1 is mostly responsible for DHT conversion in the skin.


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PostPosted: Mon Sep 14, 2009 9:52 pm 
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What's the role of 3 Adiol G in the body? Which mechanisms does it turn on and off? Does it convert in another enzime? Does it play a role in the conversion from Androstenadione to Testosterone? Some users here have shown above range levels of Androstenadione, could the lack of 3 adiol G explain this?

I' ve been reseaching on the web about 3 adiol g but there s not so much about it.


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PostPosted: Tue Oct 06, 2009 11:51 pm 
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Hi,

I had some time at lunch today and read through this paper that Mew was kind enough to post above:
"Diagnosis of 5alpha-reductase 2 deficiency.pdf"

Curious, I pulled out my urinary steroid profile from back in the May timeframe. It is important to note that at that juncture my serum T had gone from the 300 ng/dL level to 700 ng/dL level through use of low dose clomiphene citrate (see separate thread in Recoveries).

So I went through and calculated my 5 alpha to 5 beta ratios based on 24 hr urine. A couple of notes: The symbol A in the paper is androsterone. The symbol Ae is called Aetiocholamalone, I assume that is the same as Etiocholanalone. Also, the authors note that 11OH/11OHAe is not reliable in diagnosing 5 alpha reductase Type 2 activity, however mine was around 3, obviously at the extreme low end of the normal range (1.1 to 38.5)

Ratio A/Ae 5a THB/THB 5a THF/THF

Norm. Range 0.7-3.0 0.8-3.5 0.5-2.5

kazman (T=700) 1.4 1.1 0.7



That leaves me in the bottom quartile for A/Ae, and bottom 10% for the THB and THF ratios. Makes me wonder what the ratios were like prior to any TRT, or even at the end of my break from clomiphene (back on it now at lower dose).

Please quote the table and add your own ratios . . . .


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PostPosted: Tue Nov 10, 2009 3:01 pm 
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You need a doctor's requisition to get these tests, correct???

My doctor(s) I would suspect won't give me one....How do I get one?


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PostPosted: Tue Nov 10, 2009 5:44 pm 
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Quote:
You need a doctor's requisition to get these tests, correct???

My doctor(s) I would suspect won't give me one....How do I get one?


See 2nd post, pay for them yourself:

http://www.propeciahelp.com/forum/viewt ... 5058#15058


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PostPosted: Tue Nov 17, 2009 10:57 am 
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I am a bit confused about this 3AdiolG stuff.
3AdiolG is not a specific indicator of 5ARII activity, but also for 5ARI, right?
That is at least, what I find on the net and in some of the links posted here.
So, what does it really help to measure it?
Arent't the values provided by the 24hrs urine test more accurate to indicate 5ARII activity?
Further, 5 out of 8 readings of members here indicate 'normal range'. How many of them took medications or were on any kind of treatment during the test? I really don't know much this 3AdiolG but why is everybody so sure that it needs to be high? I mean it is connected to hirsutism etc... . One find nothing about the realtion to sexual sides.
If 3AdiolG is the product of both 5AR enzymes than it is as good as the measurement of DHT itself.
Maybe somebody can shed light on this for me?

I want to get this 3AidiolG checked and have an appointment next week to discuss with my uro; but I'd prefer to not only test isolated 3AdiolG, but in conjunction with other hormones - DHT, Testosterone, maybe somebody can suggest what might make sense to test in combination?


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PostPosted: Wed Nov 18, 2009 8:49 pm 
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Mew wrote:
More info on Adiol-G and 5AR: http://jcem.endojournals.org/cgi/reprint/76/4/977.pdf

Looks like the liver playes a big role, responsible for 90% of circulating Adiol-G. There is also a great diagram of 5AR metabolic pathways on page 2, with additional hormones one could test for.

Also note:

"Lobo et al. have demonstrated Adiol G production in genital skin and have shown that serum Adiol G levels correlate with skin 5a-reductase activity."


To expand the quote a little from the link mentioned above:

Quote:
Although dihydrotestosterone may be converted to androstanediol in peripheral tissues such as skin and prostate, our results suggest that the principal site of androgen conjugation to glucuronic acid is the liver. The present results cast doubt upon the role of androstanediol glucuronide as a specific marker of cutaneous androgen metabolism.


Aren't those two quotes that you have mentioned in strong contradiction? One basically says that Adio-G is not a good marker of androgen metabolism in skin (cutaneous) - the other says Adiol-G correlates with skin 5AR activity.

There doesn't seem to be much consensus here.


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PostPosted: Fri Jan 15, 2010 8:32 am 
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From http://www.propeciahelp.com/forum/viewtopic.php?t=3207


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