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DHEA-S Serum as a Predictor for Adrenal Insufficiency

Ok there has been a lot of talk about supplementing DHEA when levels are low so I wanted to address this issue. So although DHEA-S is great predictor of deficient adrenal glands, supplementing DHEA will not fix the issue because there are many more hormones produced by the adrenals that will not be optimized by DHEA supplementation. To understand this, lets look at how the adrenal glands function and what hormones DHEA can turn in to:

So your adrenal glands are 2 triangle shaped organs that sit on top of the kidney and are comprised of 2 different structures, the adrenal cortex, and the adrenal medulla. These are differentiated by the hormones they produce, the adrenal cortex produces hormones that are necessary for life, and the adrenal medulla produces hormones that are not necessary for life.

Adrenal cortex hormones are glucocorticoids, mineral-corticoids and sex hormones (IE: DHEA). The aforementioned is controlled by the hypothalamus and pituitary gland, and the latter are mediated by the kidneys. Essential for life hormones are the hormones produced that perform vital functions in the body, but as you can see by the graph below, DHEA does not convert into either of the aforementioned corticosteroid hormones. You can see in the image below every pathway that DHEA can possibly take:

So as you can see, supplementing DHEA does nothing for you corticosteroid hormones.

The two main glucocorticoids (corticosteroid hormone) produced by the adrenal cortex are:

Hydrocortisone: Or cortisol, which regulates how the body converts fats, proteins and carbohydrates to energy.

Corticosterone: This hormone is very important in helping your body reduce inflammation and it also regulates your immune response.

The principal mineralocorticoid is aldosterone, which is what helps you maintain water retention.

Now on to the adrenal medulla hormones, which are not necessary for life, but are extremely important to mood and your response in fight or flight situations. The hormones produced by this part of your adrenal glands are secreted when the nervous system is stimulated, in other words, when you are going through something really stressful.

Epinephrine: This is actually adrenaline and this hormone responds to stress by increasing your heart rate and rushing blood to the brain and muscles. It also helps regulate your glucose by stimulating glycogen in the liver.

Norepinephrine: This hormone also responds to stress but it causes vasoconstriction of the blood vessels.

So Epinephrine is primarily a hormone and norepinephrine is primarily a neurotransmitter, they do not each have their own receptors.

These hormones are extremely important to things like social behavior and memory, they are also responsible for giving you energy in times of need.

So not to go into too much detail about these hormones, all we need to know is that although they are not essential for life, they are essential for lots of other things and without these hormones and neurotransmitters you are probably going to have a lack of energy and most likely be depressed.

So as you can see simply supplementing DHEA does very little to rectify adrenal insufficiency, it may make your DHEA levels go up but you are still missing the vital hormones that the adrenal glands usually produce. Thats why in the study I posted, even though some men and women lost fat due to DHEA supplementation, it had nothing to do with rectifying the adrenals, which is why DHEA was low to begin with.

If DHEA was the only hormone secreted by the adrenals, then it would make since to treat adrenal fatigue with DHEA supplementation, but that is not the case. This is also why the literature shows that DHEA supplementation in men with high basal testosterone levels had little to no effect. DHEA basically turns into sex hormones, so if your low in sex hormones DHEA will have an effect. But if your on TRT, DHEA won’t do anything for you on its own.

This is why adrenal insufficiency is not treated with DHEA. This is why HCG is so valuable, it stimulates the adrenal glands and makes them produce all of the core hormones.

Hope this makes sense please feel free to discuss.

My endo recently told me that since am on trt taking dhea makes no sense. (Which you basically stated as well) She did ask what my cortisol was because she must have been thinking overall adrenal

Am following this thread…

Research also indicates that dhea can help with other things too. Unknown stuff.

So the adrenals have LH receptors?

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My TRT doctor at DEFY just put me on DHEA because he said my levels were fairly low. Is it actually pointless to take DHEA while on TRT?

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Well I am not saying it is pointless, I am just pointing out the fact that many are missing the point. It seems like the logical thing to do is to supplement DHEA if it comes back low, what I am saying is you also have to take HCG, at a proper dosage, to stimulate the adrenals. Because there are other hormones that are very important.

At this point DHEA may help, but not without the proper amount of HCG.

Remember low DHEA S shows the adrenals are not functioning, so if you don’t address that issue then your symptoms probably will not be rectified.

This issue is compounded by testosterone use, basically supplementing T shuts the adrenals down, and you have to take HCG if you want to offset this. DHEA alone will not remedy it.

Defy also put me on DHEA supplements when I started with them. I did not tolerate it well so I stopped taking it. Fast forward 5 years. My DHEA is above mid range with no supplements.
My suggestion. Try DHEA supplements if prescribed but if they give you issues stop taking them and just wait as see if your own goes up in time. Mine did.

What were the side effects that the DHEA caused you?

Yeah I refused the HCG since I froze sperm. I also denied AI’s with my protocol. Im just worried about what this stuff will do long term. I’m going to do all the bloodwork again in 6 weeks (3 months total TRT at that point) & see where everything falls. Then i’ll add HCG in if need be and continue the DHEA if it makes sense to do so.

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Yea the rumor is HCG is only needed if you are interested in remaining fertile, but it is not true, there are many reasons to take HCG with your TRT, this is just one of them, although this may be one of the most important reasons.

If you don’t take HCG, your adrenals are going to shut down, if they are not already shut down before you even start TRT.

Nelson Vergel of excelmale who has been on TRT far longer than most men noticed later in life his libido had dropped off a cliff and revisited HCG which only produce negative symptoms years earlier and found it restored him to his former glory.

It’s thought that shutting down his LH lead to other hormone shortages later in life, some men notice it after only a year and other years down the road where it feels like TRT is no longer working.

From Dr neal rouzier.

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I’ve been taking DHEA for several years. I’ve never thought of it as being used for adrenal insufficiency and have not heard of it from that perspective. Since I’ve used it concurrently with testosterone, I can’t say how much it helps me personally as everything seems to be working very well. However, some with only minimal to average benefits from TRT have reported significant improvement once DHEA is added to the protocol.

Well that is the point of my post, DHEA S Serum being low tells you that you have adrenal fatigue, and you most certainly need to do something about that.

We propose that the adrenal gland of an older higher primate female animal model will respond to a human chorionic gonadotropic (hCG) hormone challenge by secreting additional dehydroepiandrosterone sulfate (DHEAS). Such a response in surgically and chemically-castrated animals will provide proof-of-concept and a validated animal model for future studies to explore the rise of DHEAS during the menopausal transition of women.

These data demonstrate a positive adrenal androgen response to LH/CG in older female higher primates and suggests a mechanism for the rise in adrenal androgen production during the menopausal transition in women. These results also illustrate that the nonhuman primate animal model can be effectively used to investigate this phenomenon.

Dehydroepiandrosterone sulfate (DHEAS) levels reflect endogenous LH production and response to human chorionic gonadotropin (hCG) challenge in the older female macaque (Macaca fascicularis)


In postmenopausal women, serum LH levels correlate significantly with UFC (positively) and AER (negatively). LH stimulation may induce subtle shifts in adrenal function towards cortisol secretion.


Objective. Insulin resistance (IR) and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS). The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese) and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX) 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH) levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (; ) and insulin (; ) and positive correlation with LH (; ). Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

Adrenocortical Production Is Associated with Higher Levels of Luteinizing Hormone in Nonobese Women with Polycystic Ovary Syndrome

Now with this information we can also extrapolate that testosterone therapy induces adrenal fatigue, since it is correlated with LH and we know that is suppressed when we take exogenous testosterone.

Which is exactly the reason so many men on TRT have low DHEA-S levels, especially if they are not on a proper amount of HCG.

Interesting. I declined HCG because I have already had a vasectomy and fertility is therefore no concern. I’m interested in revisiting this in light of what you are stating here.

I’ve been on TRT for around 8 months and feel I have my protocol fairly dialed in. If I were to try adding HCG, would that affect my current T dosage? Would I have to go through dialing it all in again?

Also, what are your thoughts on this regarding females? I ask this because if it could benefit my wife as well…

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I do not think you would have to re-dial in, even though HCG stimulates hormone production it is not going to produce a crazy amount of testosterone to where you would need to lower your dosage.

Also now that you are dialed in, adding HCG should be easy to figure out, because you will know any change in labs or feeling can be attributed to the HCG.

Also remember a lot of prescribers are doling out 250iu dosages, and I can tell you that this is just not enough to do much of anything.

Also since you are already suppressed, you may want to consider a higher dosage of HCG at first while you attempt to revive and re-sensitize, then titrate down once things are moving again.

I would consider 500-750 IU 3x per week at first, then after a month or 2 drop down to 500iu 2x per week and hope that it holds.

I recommend all this to be done under the supervision of a licensed physician of course :slight_smile:

Hope this helps.

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Is dhea levels lower on trt because of a feedback loop?
Meaning more is not needed because there’s exogenous testosterone.

Also I don’t think you can dx adrenal insufficiency just because dhea is lower.
You need to check cortisol and acth levels.

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Well I used to think the same thing, until I worked with someone from Penn (one of the best for this stuff) and realized DHEA-S Serum is the best at determining adrenal insufficiency.

The truth is low DHEA-S is used for confirmation, a comprehensive questionnaire reviewing symptoms is the best way to diagnose. One of the most prominent symptoms is getting sleepy mid afternoon.

The only time DHEA-S doesn’t work well, is in elderly.

Normal age- and gender-specific DHEA-S level or a DHEA-S ratio of more than 1.78 are valuable markers of HPA integrity. Serum DHEA-S may be a candidate for a less costly approach where ACTH stimulation is unavailable.

Serum dehydroepiandrosterone sulfate in assessing the integrity of the hypothalamic-pituitary-adrenal axis

Thanks for taking the time!

I will have a discussion with Dr. Calkins and get his thoughts as well.


Is there somewhere I can go to find a good questionnaire on this. I have been getting sleepy mid afternoon lately and have been suspicious that it could possibly be thyroid but maybe this could the problem also.