How to test for 5AR/DHT activity via urine/blood test

[Mew]

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 books.google.com/books?hl=en&lr= … gsZAvVuuWM

and 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).

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%.

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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: 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.”

[Mew]

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.

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

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. "

[Mew]

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 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.

[b]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 /b."

[Quint]

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?

[Mew]

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.

[Mew]

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 – rheinlabs.com/hp.html )

… and gene mutations (ie genetests.org/servlet/access … how_flag=c )

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

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One other study also attached (Intramuscular administration of 5a-dihydrotestosterone heptanoate – changes in urinary hormone profile), with other ratios one can test for.
Intramuscular administration of 5a-dihydrotestosterone heptanoate – changes in urinary hormone profile.pdf (198 KB)
Diagnosis of 5alpha-reductase 2 deficiency.pdf (358 KB)

[solonjk]

.

[mystory]

I have found an article that states the following:

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.

[correiovip]

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.

[kazman]

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 . . . .

[mikey428]

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?

[Mew]

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:

propeciahelp.com/forum/viewt … 5058#15058

[finsucks]

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?

[awor]

@Mew

More info on Adiol-G and 5AR: 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:

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.

[Mew]

From propeciahelp.com/forum/viewtopic.php?t=3207

[Fanjeera]

Is it really so that DHT levels can be very variable in different tissues? I asked my doctor about it and he told me that, if the serum levels are fine and I’m continually balding and growing more body hair and beard, there’s no reason to think that there isn’t sufficient amount of action going on in the prostate. Or is it possible that finasteride killed only that area and let the others continue?

[martinM]

@Fanjeera

Is it really so that DHT levels can be very variable in different tissues? I asked my doctor about it and he told me that, if the serum levels are fine and I’m continually balding and growing more body hair and beard, there’s no reason to think that there isn’t sufficient amount of action going on in the prostate. Or is it possible that finasteride killed only that area and let the others continue?

Given that it shrinks the prostate by killing cells I’d say this is a given…

[adam1515]

Not sure if this study has already been posted but some more evidence of 3a-diol G on 5a-reductase activity

eje-online.org/cgi/reprint/138/4/421.pdf

[strat99]

I’m not sure if it has already been discussed, but couldn’t low levels of A-diol-g be a sign that DHT is not being broken down in the prostate (rather than that DHT is not being created)? This could lead to lower levels of testosterone b/c of the higher levels of circulating DHT… And could be due to a lack of enzymes involved in DHT to A-diol-g metabolism and not related to 5ARII. Also, if DHEA is broken down into A-diol-G as well, how do we know that low A-diol-g is related to T->DHT? Are there tests for 3Ahydroxysteroid dehydrogenase and 17Bhydroxysteroid dehydrogenase (the enzymes reducing DHT and DHEA to A-diol-g)? Let me know if I’m missing something.

[Mew]

Good discussion and insights on DHT, Adiol-G and urinary metabolite ratios to assess 5AR2 enzyme activity.

musclechatroom.com/forum/showthr … #post57536