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Author Topic: Clearance vs. Production as Explanation for Low Serum Testosterone  (Read 5563 times)

Sam

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Got my Rhein Labs Results Back and they are TELLING!!!

This is a good reference to read prior to looking at these results.

http://www.rheinlabs.com/rhien_images/05_il/05_origSter.pdf

Estrone (E1) μg/24hrs                                         4.7                            3 - 12
Estradiol (E2) μg/24hrs                                        2.2                            0 - 7
Estriol (E3) μg/24hrs                                            8.6                            1 - 16
Total Estrogens μg/24hrs                                     15                             4 - 22
Testosterone μg/24hrs                     LOW            4.9                          45 - 85
Dihydrotestosterone (DHT) μg/24hrs                   0.8                          0 - 13
Androstanediol μg/24hrs                                      60                         48 - 578 s
Androstenedione μg/24hrs                                   3.7                         Not Established
DHEA μg/24hrs                                                    1272                          5 - 1476
Androstenetriol (5-AT) μg/24hrs                          617                         42 - 710
Androsterone (AN) μg/24hrs                               2889                       798 - 4705
11b-OH-Androsterone (OHAN) μg/24hrs             1418                       461 - 1692
Etiocholanolone (ET) μg/24hrs                   HIGH 3356                       689 - 3252
11b-OH-Etiocholanolone (OHET) μg/24hrs            575                       134 - 1186
Pregnanediol (PD) μg/24hrs                                458                         32 - 501
5-Pregnenetriol (5-PT) μg/24hrs                         514                          28 - 1062
Cortisone (E) μg/24hrs                                        238                          92 - 366 s
THE μg/24hrs                                                     5525                        1365 - 5788
THB μg/24hrs                                             HIGH 329                          32 - 238
5a-THB μg/24hrs                                                499                          135 - 588
THA μg/24hrs                                            HIGH 399                           52 - 277
Cortisol (F) μg/24hrs                                         101                           35 - 168


Working on my hypotheses that I have a clearance issue and not a production issue, the data seems to indicate that could be the case.

One caveat.  My doctor had me on clomiphene that I stopped about 2 weeks prior to this testing.   My serum tests did show slightly elevated LH so it would seem to indicate my testosterone levels were a little elevate from it still.   I do not think it makes a difference because the MW of Clomifene is different enough that it should not interfere with these tests via GC/MS

Specifically my historical serum Testosterone and Cortisol and DHEA levels have been low or low/normal along with low or low/normal SHBG levels.

Based on my observation,  it looks like the data would be supportive of my hypothesis.

The key findings I see are
1) Low serum levels with high levels of Testosterone and Cortisol Metabolites in urine.
2) Low/Normal serum DHEA with High/Normal Urine DHEA

It would seem that the combined effect of clearance of Testosterone and Cortisol precursors could be as much of an issue as clearance and metabolism.

Since Etiocholanone is the primary metabolite in my urine, inhibiting 5-beta reductase could be a possible way to slow down the metabolism of Testosterone.

Question?  Can you inhibit 5-beta reductase without inhibiting 5-alpha reductase.   The reality is men with low SHBG have little DHT anyway because Testosterone doesnt hang around long enough to raise these levels.

http://www.jbc.org/content/early/2009/06/09/jbc.C109.016931

The role of this enzyme also seems to be involved in the Adenosine Pathways which I have hypothesized is the cause of fatigue in these cases as well, and why caffeine can help!

http://www.ncbi.nlm.nih.gov/pubmed/20164566

This is a double whammy that I wasn't expecting and could explain why DHEA and Pregnenolone are so helpful in low SHBG men by addressing the precursor clearance issues.
« Last Edit: February 11, 2014, 10:50:35 am by PeakT »

PeakT

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Re: Clearance vs. Production as Explanation for Low Serum Testosterone
« Reply #1 on: February 10, 2014, 06:56:08 pm »
Sam:  That is incredibly interesting.   I see what you are saying about all the androgen metabolites.

For those reading this for the first time, Sam's theory with low SHBG guys, is that they clear out their testosterone and cortisol about as fast as they get them.  This cause them all kinds of issues and makes HRT very problematic.

I'm still reading though that report.
« Last Edit: February 11, 2014, 10:50:44 am by PeakT »
THE MOST COMPREHENSIVE BOOK ON TRT/TESTOSTERONE:
https://www.amazon.com/Natural-Versus-Testosterone-Therapy-Myer/dp/1523210532/ref=sr_1_1?ie=UTF8&qid=1499116128&sr=8-1&keywords=natural+versus+testosterone+therapy
And check out my New Peak Testosterone Program: http://www.peaktestosterone.com/peak_testosterone_program.aspx
If you are on medications or have a medical condition, always check with your doctor first before making any lifestyle changes or taking new supplements.  And low testosterone is a medical condition.

Peak Testosterone Forum

Re: Clearance vs. Production as Explanation for Low Serum Testosterone
« Reply #1 on: February 10, 2014, 06:56:08 pm »


Sam

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Re: Clearance vs. Production as Explanation for Low Serum Testosterone
« Reply #2 on: February 10, 2014, 08:24:55 pm »
At the end of the day the best treatment is still going to be TRT, but I feel strongly men with low SHBG have to keep there Sertoli cells kicking.

There needs to be a "NEW" Standard of care for TRT for men with low SHBG that involves Testosterone SubQ + a FSH analog(HMG)  I dont think Clomid is a healthy option so the only realy solutions would be HCG/HMG but I am not sure HCG is actually going to do anything more for you than your own Natural production will.  i.e. Your body is all ready making a bunch of T from your own LH your just pissing it away so why replace your LH with HCG.

So you have to actually supplement with exogenous testosterone that is more than your endogenous production but not so much your Free T goes too high.   You then need to keep your Androgen Binding Globulin Levels up since they make up about 30% of your SHBG.(I think).    THis is a stop gap measure while you work on liver health and once you see SHBG get to 25-30 you could try a restart.

IMHO.
« Last Edit: February 11, 2014, 10:50:51 am by PeakT »

PeakT

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Re: Rhein Labs Results
« Reply #3 on: February 10, 2014, 08:37:16 pm »
Your body is all ready making a bunch of T from your own LH your just pissing it away so why replace your LH with HCG.


What you said makes sense, but a question about the above:

Why do you think your body was making a lot of T?  I mean I understand your reasoning, but I can't think of a way to prove it.  I guess the androgen metabolites in the urine proves it?
THE MOST COMPREHENSIVE BOOK ON TRT/TESTOSTERONE:
https://www.amazon.com/Natural-Versus-Testosterone-Therapy-Myer/dp/1523210532/ref=sr_1_1?ie=UTF8&qid=1499116128&sr=8-1&keywords=natural+versus+testosterone+therapy
And check out my New Peak Testosterone Program: http://www.peaktestosterone.com/peak_testosterone_program.aspx
If you are on medications or have a medical condition, always check with your doctor first before making any lifestyle changes or taking new supplements.  And low testosterone is a medical condition.

Peak Testosterone Forum

Re: Rhein Labs Results
« Reply #3 on: February 10, 2014, 08:37:16 pm »


Kwn

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Re: Rhein Labs Results
« Reply #4 on: February 10, 2014, 09:14:30 pm »
Sam,

uros and endos do not even have reasonable 'standards of care' for men with normal SHBG, leave alone low SHBG.  They still go by "200 mg per 2 weeks or 100 mg per week", refuse to recognize importance of estrogen.  My first uro said 'estrogen is a problem only for fat people', estrogen of 40 is normal.  I do not quite understand how these people justify existence of HRT clinics for themselves.  There are HRT clinics, with tons of patients, they follow different protocols, many times successfully.  And yet uros and endos seem to be blind to that fact.  How do you explain that?  Being bound by current 'standards of care'?  Legal considerations (malpractice insurance etc.)?  Just general dumbness, even after 8 years in med school?  This could be the case, but it happens on such a massive scale it is an impossibility...
« Last Edit: February 10, 2014, 09:16:29 pm by Kwn »

Sam

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Re: Rhein Labs Results
« Reply #5 on: February 10, 2014, 09:44:01 pm »
The reality is personalized medicine is coming but slowly.   Part of the problem is reimbursement and part is just old school docs who think everyone should fit within the bell curve.

Its frustrating for us that dont fall within the bell curve, but you have to realize your breaking new ground and part of a movement that will revolutionize healthcare if done properly.

You need to become an "E Patient"  and accept it.

http://en.wikipedia.org/wiki/E-patient

There are thousands of people much worse off than any of us on this board with terminal cancer and they are dealing with the same bullshit as we are on this board.       This is my attempt at being an E Patient for low SHBG Hypogonadal men.

Peak,  since all of the unit are microgram, yes I think this shows production is not an issue and this is highlighted since serum levels are low and urine levels are high or high end of normal.

davie12

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Re: Rhein Labs Results
« Reply #6 on: February 10, 2014, 10:01:01 pm »
Sam...sorry in advance if my questions are partially off topic. I'm going to be using Rhein Labs sometime later for some testing, so maybe I can learn from your experience.

1) Insurance: Did you get this covered by insurance entirely or did you have to get an "out of network" referral like I will where you have to file a bunch of paperwork to get partial reimbursement (after paying out of my own pocket in advance)?

2) Was this administered by urinating 4 times during the day into containers? For the cortisol reading, isn't the meaningful measure the specific amount excreted from one's body at a specific time in the day? It looks like your cortisol reading is one number that I assume is total cortisol excreted during the 24 hours...unless I'm not understanding something?

3) The Testosterone reading is low. I thought the prototypical low SHBG person would be excreting a high level of testosterone...ie. high clearance out of the body resulting in low serum at a given point in time?
Recovering from adrenal fatigue through Paleo diet+exercise+vitamins/supplements; formerly used HCG & Clomid at various dosages

Sam

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Re: Rhein Labs Results
« Reply #7 on: February 10, 2014, 10:02:21 pm »
This could explain why Licorice Root Extract has always made me feel better.  Its another stop gap measure but worth noting that it could slow down metabolism of Testosterone and Cortisol in low SHBG men.

http://www.ncbi.nlm.nih.gov/pubmed/2326827

Quote
The effects of the licorice derivative, glycyrrhetinic acid, on hepatic 3 alpha- and 3 beta-hydroxysteroid dehydrogenases and 5 alpha- and 5 beta-reductase pathways of metabolism of aldosterone in male rats.
Latif SA, Conca TJ, Morris DJ.
Author information
Abstract
Ingestion of licorice or treatment with chemical derivatives of glycyrrhetinic acid (GA), an active principle of licorice, can cause hypertension, sodium retention, and hypokalemia. Although GA has been shown to inhibit 11 beta-hydroxysteroid dehydrogenase, it may not be the only hepatic enzyme affected by this licorice derivative. Therefore, we studied the effects of GA on other major hepatic steroid-metabolizing enzymes from adrenalectomized male rats using aldosterone as the substrate; namely, delta 4-5 alpha- and delta 4-5 beta-reductases and 3 alpha- and 3 beta-hydroxysteroid dehydrogenases (3 alpha- and 3 beta-HSD). From these in vitro studies, we demonstrated that GA does not affect either microsomal 5 alpha-reductase or cytosolic 3 alpha-HSD activity. However, GA is a potent inhibitor of cytosolic 5 beta-reductase; the K(is) and K(ii) were calculated from enzyme kinetic analysis to be 6.79 and 5.41 microM, respectively, using the Cleland equation, indicating that GA is a noncompetitive inhibitor of aldosterone. In addition, GA specifically inhibited microsomal 3 beta-HSD enzyme activity by what appears to be a competitive inhibition mechanism, causing a build-up of the intermediate, 5 alpha-dihydroaldosterone (DHAldo). Thus, this study has indicated that GA has a profound effect on hepatic ring A-reduction of aldosterone. Inhibition of 5 beta-reductase and 3 beta-HSD results in decreased synthesis of both 3 alpha, 5 beta-tetrahydroaldosterone (THAldo) and 3 beta, 5 alpha-THAldo and, hence, accumulation of aldosterone and 5 alpha-DHAldo, both potent mineralocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)

Sam

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Re: Rhein Labs Results
« Reply #8 on: February 11, 2014, 10:57:42 am »
Sam...sorry in advance if my questions are partially off topic. I'm going to be using Rhein Labs sometime later for some testing, so maybe I can learn from your experience.

1) Insurance: Did you get this covered by insurance entirely or did you have to get an "out of network" referral like I will where you have to file a bunch of paperwork to get partial reimbursement (after paying out of my own pocket in advance)?

2) Was this administered by urinating 4 times during the day into containers? For the cortisol reading, isn't the meaningful measure the specific amount excreted from one's body at a specific time in the day? It looks like your cortisol reading is one number that I assume is total cortisol excreted during the 24 hours...unless I'm not understanding something?

3) The Testosterone reading is low. I thought the prototypical low SHBG person would be excreting a high level of testosterone...ie. high clearance out of the body resulting in low serum at a given point in time?

1) The cost was $225.00.   You have to pay $50.00 upfront for them to ship you the kit.  They will try and work with your insurance, but I beleive most will be an Out of Network cost after you satisfy your deductible.  I havent completed this yet so will update more later.

2) The Urine collection is everything for 24hrs.    Urine testing tells you how your total production is compared to a snapshot.   A normal diurnal pattern is probably equally important, so I would suggest a 4 point saliva in conjunction with Free and Total Cortisol and Cortisol Binding Globulin.   (I did all of these also)

3) ETIOCHOLANOLONE is a major metabolite of testosterone in Urine.   You have to look at the link I provided and assess the results in that context.   This includes cortisol metabolites.   I think the low T in urine is even more proof that your issue is the rapid excretion of unbound testosterone via urine metabolites.  YOu wouldnt expect much actual Testosterone or you probably have a different problem.

http://press.endocrine.org/doi/abs/10.1210/jcem-18-10-1056

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Re: Rhein Labs Results
« Reply #8 on: February 11, 2014, 10:57:42 am »