DHEA

DHEA, THE UNIQUE AND INDISPENSABLE HORMONE

DHEA keeps function normal in all our cells.
But we reduce DHEA production by 1% per year, from age 26.

So the blood level of DHEA in old age is 10 % or less of that at age 20.
That’s the root cause of a lot of our problems.

DHEA,THE MOTHER OF TESTOSTERONE

conversion of cholesterol to DHEA and the neurosteroids

DHEA” is an acronym for DEHYDROEPIANDROSTERONE, the hormone produced in greatest quantity by youthful human and other primate apes. (1)
In smaller animals, the hormone is only produced in the brain, so blood levels are low.
The brains of humans and the Primates also make DHEA: small amounts are made in the gonads and by the skin; but in addition human and primate adrenal glands process cholesterol into Pregnenolone.
Then, from Pregnenolone, they make DHEA in such large amounts in youth, that weight-for-weight, it exceeds the aggregate of all the other hormones. (1)

DHEA levels are high at birth, because the mother produces large amounts during pregnancy and the hormone crosses the placenta to the baby.
Levels fall rapidly after birth and remain low until “adrenarche” at age 8, to 13 or so, at which point both males and females begin to maximise DHEA production.
See the graphic below and for detail, see the website, “YOU and YOUR HORMONES“,or read about adrenarche in Wikipedia (the Wikipedia article is the easiest one to read).

DHEA production and delivery to the cells

DHEAS, a water-soluble, Sulfated form of DHEA, is released by the adrenals and circulates in the blood.
The amount produced varies through the first 20 years of life, as shown in Figure 2 (from “YOU and YOUR HORMONES“).
The high DHEAS levels, from the 8th week after conception to birth, are due to high production by the mother: children’s blood levels from birth to Adrenarche is low.
Caveat:
This graph gives an excellent impression of the variation in the level of DHEA, but it is inaccurate from age 14 to age 20: normal adult DHEA levels in the 2nd and 3rd decades are 12-14 micromoles/litre for males and 10-12 micromoles/litre for females.
So in the teen years, the red line in the graph should rise to the level at birth, or higher.

Figure 2, DHEA levels in the fetus, from birth to Adrenarche and in the “teens.”
Graph: Serum DHEAS, in pregnancy, adrenarche, and to age 20
Normal serum levels of DHEAS, during pregnancy and up to age 20
How the cells use DHEAS

DHEAS is absorbed by all cells in the body and is converted to fat-soluble DHEA.
Each cell then uses enzymes (its personal mix of “3 beta hydroxy-steroid dehydrogenase” enzymes), to change DHEA into the “micro-hormones” it needs to function efficiently.
This is why your fingers make fingernails and your hair roots make hair, while special cells in your bones make blood, et cetera.
Hormone production inside the cells was labelled “Intracrine hormonogenesis” by Prof. Dr. Fernand Labrie in 1980. Dr. Labrie, then Professor of Endocrinology at Laval University, Québec, is now deceased.

Beginning at age 25-30 in females and 30-35 (or earlier) in males, DHEA production by the adrenal glands falls by approximately 1% – 3% per year.
So by age 80 the blood contains mainly DHEA made by the brain and the blood level in old age is 10 % or less of whatever it was at age 20–25 (it may in fact, fall to zero).
However taking DHEA by mouth can keep its levels up and allow normal function.

Figure 3: DHEA levels into old age, Vs liability to cancer and other diseases.

This is a version of a graphic by dePeretti & Forest 1976, Parker & Odell 1980, Vermuelen 1980, Orentreich et al. 1984, Labrie et al. 1997 , redrawn by J.W. Nyce.
It shows NATURAL DHEAS blood levels in humans, vs. animals and illustrates the effect of DHEA levels on cancer risk.

I copied it from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106910/ .
I have reproduced it here because the blue and grey lines clearly show what happens to humans’ DHEA level as we age, the red line points out our liability to cancer and, by inference, degenerative diseases*, while the green line shows the liability of other animals.

* The % risk differs among diseases, but the general trend is the same.

For further explanation, see my paraphrase of Dr. Nyce’s notes, below the graphic.

DHEA in men and women, Lifetime Human vs. animal lifetime cancer risk
erc-25-R497-g004.jpg

Figure 3, explanation:
In humans, circulating DHEAS (blue and grey lines) is maintained at optimal levels only until about age 25 years, which is our prehistoric life expectancy.
Because we now live much longer than we were originally designed for,
increasing risk is observed as age increases (red line).
(http://www.cancerresearchuk.org/health-professional/cancer-statistics/incidence/age).
The red line shows a human lifetime cancer risk of 38.4%.
The green line shows the cancer risk of most long-lived mammals: 4%
(Abegglen et al. (2015).(https://www.cancer.gov/about-cancer/understanding/statistics).
Caveat: the trend of the red and green lines line are similar for all degenerative diseases, but the numbers “38.4%” and “4%” only apply to cancers.

HIGH AND LOW DHEA PRODUCERS

As with everything in nature, there is a Bell-curve spectrum of DHEA levels in youth and there is a lifelong difference between the highest and lowest producers.
In the case of DHEA however, the curve is “skewed” to lower levels on the left: this is because victims of abuse, or other sources of childhood PTSD, tend to under-produce DHEA in the teen years and through age 25.
People with the lowest production in the “teen years” can get to “80-year-old” levels in their 20s and tend towards a zero level in old age, because that 1%–3% per annum loss applies to whatever level the body is producing at age 25.

So a deficiency of DHEA can be found at any age and can cause inefficiency of hormonal function in any part of the body, including the central nervous system, the “immune system”, the heart, the thyroid, and everything else.
Even personality and psychology, particularly in the area of self-confidence, may be affected.
Because of this, the symptoms of deficiency vary from person to person, depending on which organ, or which function, is most sensitive to low DHEA.

CAVEATS
(1) Because DHEA is raw material for hormone production, DHEA deficiency causes deficiency of other hormones, such as progesterone, allopregnanolone, testosterone etc., even in the 2nd and 3rd decades of life.
Therefore the symptoms of DHEA deficiency are extremely variable and correcting low DHEA produces improvement in many conditions.
(2) There is an exception to the above picture: women with PCOS (polycystic ovarian syndrome) overproduce DHEA.
PCOS is characterized by irregular menstruation, hirsutism, obesity, diabetes with or without metabolic syndrome, infertility and psychological stress with depression.
Most PCOS patients overproduce DHEA and continue to do so, with no yearly loss of production.

ABOUT DHEA AS A SUPPLEMENT

DHEA AND DOCTORS
The subject of DHEA is a bone of contention in the medical community:
there are 3 “teams”:
(1) A small group of enthusiastic doctors think, as I do, that everybody should take DHEA so as to keep the body’s maintenance and repair systems working for as long as possible.
(2) Researchers who mostly agree with that.
(3) Naysayers and doomsayers, whose objections are such as “What If?”, “Perhaps interfering with your hormones might be harmful”, “It hasn’t been tested”, “compounded pills are of poor quality” and “We don’t know, so it’s not recommended”.

OVER-THE-COUNTER DHEA
DHEA has been “OTC” in the USA since 1995 and as Dr. Fernand Labrie, Professor of Endocrinology at Laval University. and a premier expert in the field, said in 1988: 
“No serious adverse event related to DHEA has ever been reported in the world literature (thousands of subjects exposed) or in the monitoring of adverse events by the FDA (millions of people exposed)”.
Now, more than 30 years later, Professor’s Labrie’s statement still holds true:
Maintaining DHEA keeps bodily functions normal.

DHEA SUPPLEMENTATION: Maintaining DHEA keeps function normal.
Maintaining DHEA, at the level usually found at age 25, keeps function normal.
DHEA is the raw material for a range of essential hormones, so keeping it freely available tends to “fix everything”, just as Thyroid Hormone 3 maximizes the efficiency of all our cells.

Examples of DHEA’s beneficial effects
[1] DHEA helps to maintain thyroid hormone balance by reducing Cortisol
Cortisol “short-circuits” thyroid hormone function by blocking the processing of T4 into active thyroid-3 hormone. Further, it encourages conversion of any available thyroid-3 into inactive thyroid-2. *
Thus cortisol causes slowdown of all cell functions: for example, the hair follicle cells can’t make hair and the hairs fall out (you’ll see folks with the outer 1/3 of their eyebrows and all the hair on their legs gone), the skin gets dry because the oil producing glands shut down, the voice gets hoarse, the muscles ache, the legs swell, constipation becomes a problem and cognition suffers.
All of these symptoms improve when DHEA levels are restored; things don’t go back to 100% normal unless the thyroid hormone is restored too, but they improve with DHEA alone.
[2] DHEA helps depression in teenagers, “20-30s” and older folks too. **
[3] DHEA helps in Lupus, improving symptoms, in AIDS, and in many other diseases.
[4] It helps female sexual dysfunction by raising the Testosterone level. ***
[5] It helps male sexual dysfunction by raising the Estrogen level. ****
[6] It maintains heart health and reduces the incidence of “cardiac events”.
* In high-stress conditions, DHEA normalises intracellular thyroid 3 by reducing cortisol production: the resulting cellular efficiency is expressed in all areas, including the brain; so there is better cognition and reduced “fuzzy thinking”:
see ” “INTRACELLULAR HYPOTHYROIDISM“, in the page on Thyroid Hormones.
** In depression, DHEA increases Testosterone, which improves self confidence, reduces percieived stress, lowers anxiety, eliminates compulsive thinking and prevents worrying.
It helps to correct Allopregnanolone deficiency (the real reason for depressive states of all kinds).
*** Female sexual dysfunction begins when DHEA is below 5.0 pmol/litre, at any age.
**** When men take DHEA, some is “aromatized” into estrogen by the liver: the estrogen does no harm and without estrogen in the system, there is complete loss of libido: both men and women need estrogen to maintain sexual interest.

CAVEATS:
Low DHEA is a part of the circle of despair which generates depression.
Low DHEA is a lifelong condition. The 18-Year-Old with low DHEA is not going to reboot his hormone production just because you got him to supplement with DHEA for a year.
Every low-DHEA sufferer needs to continue supplementing it permanently.
Symptoms recur 3-4 months after discontinuing DHEA, (Observation, from 606 cases, treated between 2006 and 2014).

ABOUT DHEA AND YOUR BRAIN

The brain does not depend completely on adrenal production of DHEA: it makes DHEA for itself, but it is unable to make as much as it needs to manufacture Pregnenolone, Progesterone, Allopregnanolone and Testosterone.
Supplementing with DHEA improves the brain’s production of those “downstream” hormones, providing enhanced self-confidence and a brighter mental outlook, increased cognitive speed, better sleep, efficient brain cell maintenance, sharper memory and mental relaxation.
These improvements can be observed in everyone whose serum DHEA is less than 6 micromoles per liter (µmol/L) before treatment.**

** 606 low-DHEA patients were seen and treated in Etobicoke, 2006 to 2014 and 200 in Collingwood, 2015 to 2021): almost all (males and females) had a DHEA blood level of less than 6.0 µmol/L when first diagnosed.

DHEA AND CANCER

DHEA AND PROSTATE CANCERA CASE REPORT

A 62-year-old man with BPH (Benign prostate hypertrophy), developed a PSA of 5.09 (normal = <4.0) in December 2011.
A biopsy showed a Gleason 6 prostate cancer, in 1, out of 14, biopsy cores.

After in-depth discussion, he agreed to try DHEA and I prescribed 100 mg per day
(later on, his dose was reduced to 50 mg daily).

He was followed closely with PSA tests, because in the usual course of prostate cancer, the PSA goes up continuously.
His PSA did not go up: it gradually went down and by December 2012, it was 4.1.

A repeat, ultrasound-guided biopsy in December, 2012 showed only “PIN”
(Prostatic Intra-epithelial Neoplasia), the earliest form of prostate cancer.

He continued with DHEA, 50 mg/day.
In July 2014, a repeat biopsy showed no cancer.
DHEA was then discontinued and he has not taken it since.

His PSA fluctuated over the years, with highs of 4.76 in January 2017 and 6.68 in 2021, but it did not rise steadily, as it usually does with prostate cancer.
The elevations were due to his progressing benign prostate disease.
In 2022, he was unable to urinate because of the enlarging BPH and a “TURP” (Transurethral Prostate Resection”) was done in August of that year.
No cancer was found in the surgical specimen.

A month later, he had some complications of the surgery and the resection was repeated in October, 2022:
The new surgical specimen showed no cancer, either.

CONCLUSION: in this case, a biopsy–proven prostate cancer was cured with DHEA.


ABOUT DHEA AND YOUR HEART

DHEA reduces our liability to heart attacks: here are two case reports:

Two of my healthiest male patients:     
Harvey, 66………………………………………………………………………………………….Herman, 65
(not their real names)  

Two identical patients

 Back in 2006 two of my healthiest male patients, one aged 65 and the other 66, developed “multiple extrasystoles”
(extra heartbeats, with no other problems)
at the same time.
I advised them to take DHEA, because DHEA keeps heart function normal.

Herman did, Harvey didn’t.
Herman was fine, and had no more extrasystoles.
Harvey progressed to atrial fibrillation in 2009 and had “defibrillation” (electric shocks, to reset his heart rhythm) done, on two separate occasions.
The fibrillation returned and an ablation (burning the over-excitable spot inside the heart) was done.
Later on, in spite of multiple-drug treatment, he had to have a pacemaker put in.
In 2014 he needed stenting of three heart arteries for blockage and in 2020, he had a quadruple heart-artery bypass.
In December of 2022, thinking about Harvey and wondering how he was doing, I called him on the phone: now 84 years old, he said that he was doing well, but he sounded “old and tired”.
I reminded him about my advice regarding DHEA: he said that he had never taken it, but that he would get some and start it as soon as he could.

In February, 2023, I called again: he had taken 50 mg of DHEA daily from the end of December, 2022 and he feels very well and much stronger. I wished him well for his birthday, in June.

Harvey’s 84! That sounds great, but let’s compare his experience with Herman’s story:

Herman started taking DHEA, 100mg per day, as soon as he got it (August, 2006).
He took 100mg daily, until the summer of 2017, when he developed the only male side-effect of DHEA: breast enlargement and tender breast cysts.
That was terrible. He said he was going to change his name to Hermione, but he Let me talk him out of that and I reduced his dose to 50mg.
The problem went away in ten days and he has taken 50mg, since (now Aug. 2023).**

In March of 2000 he had a brief runny nose, then “Covid toes”, and later on had a combination of a super-itchy rash, shortness of breath and rapid heartbeat.
The symptoms improved slowly: I figured they were from “Long Covid” and advised him to wait.

The itch improved with a Corticoid cream, “Liderm”, prescribed in December of 2020, but the heavy breathing and fast heartbeat continued.
In April of 2021 I sent him to a cardiologist and a respirologist.
He had an EKG, a chest xray, echocardiogram, exercise stress test with Persantine and a CAT scan of the chest with “contrast” angiogram.
All tests were normal.
The Cardiologist reported that Herman’s 82Y-O heart is perfect, with no evidence of disease in the arteries or any other abnormality.
Through the summer of 2022, he resumed his exercise program and the shortness of breath/rapid heartbeat problems have gone away.
He is well.

So, at least based on these two cases, restoring DHEA to more youthful levels by supplementation can protect the the heart from major cardiovascular risk factors which lead to problems from heart-artery blockage.

Keep your DHEA up

Ladies and gentlemen (both), keep your DHEA level at “25Y-Old normal”, or higher:
it’s the best thing you can do for your body.
Remember this: maintaining DHEA keeps function normal.
If acne, oily skin or hair-on-the-chin begin to bother you when you take it, reduce your intake, but don’t stop it altogether.

All the other hormones, vitamins, minerals etc are important and should be supplemented too, but DHEA supplementation is a “must”.

** Herman took DHEA by itself until 2014, so it is safe to say that his extra heartbeats were stopped by the DHEA, and not by something else.
He started adding vitamins and other supplements in 2014 and now (2022) takes 2,500iu of Vitamin D, 2 grams of Vitamin C, 1 mg of Vitamin B9, a multivitamin, 200 mg of Magnesium Threonate, Fish oil, Primrose oil, 50 mg of Progesterone, 2 g of L-arginine, 900 mg of NAC, CoQ10, 100 mg of Nattokinase and 10 mg of Melatonin.

He was diagnosed with intracellular hypothyroidism in 2015 and takes T3 for that.

Now aged 84, Herman’s vision is slightly “cloudy”– he has cataracts, which started in 2011, but they are progressing only slowly, perhaps because of the DHEA and T3.
He has begun to wear glasses for reading, but does not need them otherwise.
His high-frequency hearing is slightly reduced, but he does not need hearing aids.

He exercises in a gym, has a BMI of 25.5-26 (5′,10 1/2″, 169-173Lb), plays pickle ball.

THE BOTTOM LINE:

Maintaining DHEA keeps function normal.
As the DHEA supply falls after age 25, something is bound to go haywire; but supplemental DHEA will maintain youthful levels, allowing ongoing “Downstream hormone” production and facilitating normal body function.
Note that of course, production of all hormones falls as we age, so for best results, you should regularly assess your hormones and supplement each one as necessary.

Note also that age-related hormone loss is irreversible, so that ongoing, lifetime supplementation is necessary.
Although the age at which supplementation becomes necessary varies, 100% of humans will benefit from DHEA supplementation, beginning at age 26, or at the latest, when the serum level falls below 6 µmol per litre.

REFERENCES

In Lieu of references, I have provided Links to the appropriate websites; but 2 sources are worth mentioning separately:

(1) Campbell B (2020) DHEAS and Human Development: An Evolutionary Perspective.
Frontiers in Endocrinology | http://www.frontiersin.org 1 March 2020 | Volume 11 | Article 101Front. Endocrinol. 11:101, doi: 10.3389/fendo.2020.00101
campbelb@uwm.edu

(2) Fernand Labrie: DHEA, important source of sex steroids in men and even more in women, in Prog Brain Res. 2010;182:97-148, PMID: 2054166
doi: 10.1016/S0079-6123(10)82004-7.