T Nation

DHEA and Pregnenolone Help


I am 47. Had one testicle removed 20 years ago. Been taking 25mcg cytomel daily for a few years. 4 years ago, I decided to look at TRT. My TT was 260. So, tried the T-cream for 1.5 years, but it did nothing for me and it never changed my readings.

So, I switched to shots ever 3-4 weeks. Felt great for the first 1-2 weeks, then bad. Finally stopped the shots after 9 months because I gained too much weight, plus the last 6 months shots were not making me feel good. Did not know about E2 then.

Stopped everything for one year. But, I was having a lot of afternoon brain fog, so 6 weeks ago I started TRT shots again. The first week, I felt really, really good. But, the second and third weeks were horrible! I was having major hot flashes and zero energy.

That is when I learned about this site. So, I switched to self injecting 50mg, 2x/week in outer quad. I would feel good the first day, then bad. I would feel puffy and fatigued the next few days.

So, last Wednesday I insisted my doc test my blood. I asked for the blood panel per the first sticky on this website. However, I know that E2 must be high because I already have the man boobs going on. So knowing that the T-shots would do no good with high E2, I temporary stopped the shots until I got adex.

On Friday evening, I received adex. So I took another T-shot and my first adex dose. I felt much better Saturday, but not so good Sunday and this morning. The Saturday high was probably from the T.

For the last week, I have been having heart palpitations badly. It seems to be somewhat better when I take 5mg of cortisol, but it does not totally disappear. Plus, I still do not feel great. I am not taking hcG because my family doc will not do it.

However, I am considering DHEA and pregnenolone. I will admit that I do not understand the whole TRT/Adrenal/Thyroid connection. I am hoping someone can explain. Here are some of my questions:

  1. Is taking DHEA and/or pregnenolone a substitute for taking hcG if you are not concerned about fathering or shrunken testicles? It seems to make sense because DHEA and pregnenolone can convert to other hormones that your body needs.

  2. Is it correct to say that if you are not on hcG, then you should be on DHEA and pregnenolone?

  3. If my adrenals are in need of cortisol, will taking pregnenolone solve the problem, since my body can convert it to cortisol?

  4. Does TRT put more burden on the adrenals? If so, can you explain why? I feel like it must because I did not a problem until I started TRT.

Please excuse me if I have overlooked information. I have tried reading all I can on this website but I have not found answers to the questions above. KSman has been a big help so far รข?? thanks, guy! But, I do not want to overburden him with questions. Any insight is appreciated!


I am no expert, but it does seem to me like you should give the T plus Adex time to stabilize in your system before you make any decisions to include alternate/additional meds. Some are in favor of adding DHEA to TRT, others are not. If I were you I would wait until my next blood draw and see where your levels are at.

If your E2 is still high, or T too low (or too high) then adjust dosages accordingly. I know from experience that waiting can be a pain in the ass, but it does take time to get everything right.


the whole TRT/Adrenal/Thyroid connection is extremely complex. I have given up fully understanding it unless I want to go to medical school - but even then (given the quality of doctors today) I am not sure I would actually learn anything helpful.

oral DHEA increases the creation of the CyP3A4 enzyme. The CyP3A4 enzyme inactivates drugs, toxins, and various hormones, allowing the metabolites to be excreted.

more DHEA = more CyP3A4 enzyme = faster clearance of DHEA from your system along with everything else. The more DHEA you take, the more you need to take.

Oral Pregnenelone can convert via the 5-ar effect during the first pass through the liver and then it can act like valium and can be very sedating/depressing. People with above average 5-ar activity probably have this problem.

Either way it probably takes your body a bit (a few days to a few weeks) to detect and respond to the elevated oral DHEA/Pregnenolone levels and then you get the counter effects - so you go loose the benefits you saw at first.

1) HCG mimics LH. Preg and DHEA do not mimic LH. Hopefully HCG stimulates the 'natural' pathways for hormones to help the body stabilize itself. If you don't use HCG then yes, your pregnenolone levels will be lower which also means your DHEA will probably be lower.

2) possibly, but see the info above. The only way around the liver first pass is to take lipid matrix micronized pregnenolone and possibly lipid matrix micronized DHEA (or Keto-7 DHEA??? no idea on this one) or to use Transdermal Preg and/or DHEA, but some people can't absorb transdermal and very few if any (from what I have read/found) actually see increases in preg/dhea levels when using TD - there just is not enough getting into your system.

excess DHEA above your bodies optimal point will convert readily to extra T which will then convert to Estradiol. I had to eliminate all oral DHEA because of Estrogen problems.

3) possibly. pregnenolone CAN convert to Progesterone. Progesterone CAN convert to Cortisol. but they can also convert to a number of other hormones/steroids. Some people taking the lipid matrix micronized pregnenolone have had to reduce or stop their cortisol - but it is an ongoing "study" with forum members since mid-June.

4) yes, it can. If you system is already run down (which it should be if your Testosterone is low) then your other systems are probably burned out. Correcting your T will then return the 'normal' strain to these systems which won't be able to keep up with the increased demand - and you crash. Think of your body as a run down car - bad brakes, bad transmission, balding tires, bad engine, bad gas, etc. - now you put in a brand new high performance engine (i.e. - extra T), how will all of the other systems respond? They could keep up with the older lower performance engine, but will probably break down completely and possibly catastrophically if pushed to hard by the new engine.

Heart palpitations can be caused by many things including hyperthyroidism. Extra cortisol = better functioning Thyroid = possible hyper symptoms maybe?

were you able to get everything recommended on the blood test sticky?

what were you on when you had your blood drawn? what day were your doses taken?

why are you on cortisol? and why only 5mg? most docs go for replacement or 15-20mg or more. 5mg just shuts down your natural production of cortisol (i think).

what were your original blood test results before you started HRT?


Any links documenting "more DHEA = more CyP3A4 enzyme = faster clearance of DHEA from your system along with everything else. The more DHEA you take, the more you need to take. "


DrMariano (Physician, Psychiatrist)

I have no idea if the links below reinforces the concept or not - as these studies are completely way over my head - but it shows that there are studies about this - and Mariano's concept seems plausible.

Here is a study that shows that DHEA reduces certain enzyme activity - not CyP3A4 - but it shows oral DHEA does have an effect on enzyme activity - so it is not hard to imagine that it can also increase certain enzymes - http://onlinelibrary.wiley.com/doi/10.1002/ijc.11075/pdf


I think you are correct in that I need to allow my system to stablize after starting the adex. I just wanted to ask in case I am already on the wrong tract.

I had the palpitations before I took cortisol. I took 5mg cortisol each time to reduce them. I understand 15-20mg is a physiological dosage that the adrenals put out per day. Since cortisol wears off within a few hours, I split the dosage into 5, 5, 5 or even 7.5, 5, 5.

I also thought that since TRT raises metabolism, that I could cut back on cytomel. Tried it for one day and about died - the palpitations were extreme. All of this points to me that it is not hyperthyroid.

These are the blood markers I requested: FT, TT, TSH, E2, LH, rT3. I had my blood drawn midway between my 50mg injections. I injected on Monday PM and had blood drawn Wed AM. The next injection was Friday AM. Before TRT, my TT was 260. That was all we tested for because I did not know about this site.

It makes perfect sense that with the addition of T, my metabolism is rising and the adrenals are not ready for it. So, what should someone do to help strengthen the adrenals to get them able to handle the higher metabolism? (That is actually what starting this question, because I thought pregnenolone was the answer....)


www.ncbi.nlm.nih.gov/pubmed/12642469 Is this really about orals? Injected or transdermal DHEA would have a different result? I think that the issue is that steroids affect CYP3A4 metabolism of other things, not that CYP3A4 is decreased. When liver enzyme pathways like this are loaded up with a substance, the pathways are less able to process other things, such as drugs, which can extend the half-life of the drugs which can lead to dosing errors.

You can say the same thing about hundreds of substances, not just some steroids. The study indicates that enzyme activity is reduced [on some other things]. Does not support the idea that enzyme levels are changed. And what was the point? Same issues regarding TRT. You are suggesting that we not take DHEA and do not do TRT?

Drink too much grapefruit and that can mess up some heart medications, reduce clearance of estrogens which lowers testosterone. Nothing new. Restoring DHEA-S to youthful levels will create the liver enzyme issues of a young healthy male. Are we looking for a problem that does not exist?


Adrenal fatigue recovery takes a long time. You cannot take a pill to fix it. Read Wilson's book "adrenal fatigue".


I just got my blood results back!! These were taken on a Wed AM. I had done 50mg shot on Monday PM. Also, I take 25mcg Cytomel daily, but took a smaller dosage on Tuesday. Don't know if that messes up anything or not.

E2 = 24 (0-47 pg/mL)
LH = 1.1 (1.2 - 8.6 iu/L) report says low
T3 Resin uptake = 38 (32-48%). I don't think they did the right test. I don't know what resin uptake is.
TT = 748 (Quest) They did not give range
FT = 178 (report says high)
% Free Testosterone = 2.38 (1.0-2.7) Report says High
TSH = .572 (0.4 - 4.0 uU/mL)

Can anyone comment about these?? On the day I had the blood taken, I had low energy, but not bad heart palps. The really bad day was the day before.


I am sorry, but the test results are not really all that helpful - except to show your T and E don't look bad.

It would have been helpful to have a complete panel, but you are missing:
Vitamin D
Reverse T3
Free T4
Free T3

no need to test LH. LH will always be low when you are on HRT.

what were you on (all supplements, vitamins, medications, etc) when you had your blood drawn?

what were your original blood test results before you started HRT and/or cortisol?


TT is quite decent. But FT is the winner if shown as high. If FT is great, ignore TT.

Note that FT ranges vary greatly from one lab to another and cannot be compared without the ranges. And ranges on lab reports are often age adjusted. You need to compare to youthful ranges.

So you started anastrozole Saturday after doing lab work Wednesday?

What T protocol and for how long before the lab work? With E2=24, you are probably going too low.


also missing SHBG


3 years ago, my TT was below 300. So, I was on TRT gel for 2 years and shots for 1 year. But I quit all of that last year. So this year when I wanted to start back on shots, he just did the TT, which was 260 in mid-June. I did not know about this site then.

When I went to have my blood done last Wednesday, I looked at the sticky and looked at the labs needed after you start TRT. I had every one of those labs done except for FSH. It was an oversight. I did not get DHT because it said it was a waste of time if T is low (T=260=low). Also, I did not get Prolactin done because it said it was optional. SHBG was not listed as required. Last, the PSA is going to be tested at work in 2 weeks at our annual health fair, so I did not want it done twice.

KSman, when you say FT is the winner because it is high, do you mean that too much FT is my problem? The report did not show a range, but it did say Quest. And, yes, I started anastrozole on Saturday Aug 7 after doing lab work on Wed Aug 4. On June 29, I had my first T-shot in hip (200mg). Three weeks later, on July 20, I started doing 50mg shots myself (2x/week). My 5th shot by myself was on Monday eve, Aug 2. That following Wed AM (Aug 4) is when I had by blood taken. So when E2=24, I had not done any anastrozole ever.


BTW, the range for my FT is 35-155. That is why my value of 178 is HIGH.


High FT is where one wants to be. Some docs do not even test TT for ongoing TRT.

Ranges for FT vary from lab to lab. If your E2 is building, FT will go down.

If FT is high, is not a problem, thus no need to test.

Never test LH/FSH ongoing with TRT as these will be close to zero. A one time on-TRT FSH test can be done and if not low that would indicate a type of testicular cancer; which is a younger man's risk.