DHEA and DHEA-S

CS: What does it mean if you are low on DHEA or DHEA-S? Many of my previous blood tests have stated that I am at the low end of DHEA-S. Does this affect my hair loss at all?

I also have low DHEA and am now on a bio-identical cream of estrogen and dhea mixed together. My progesterone and testosterone were also low and I am supplementing them also. I believe hormones definitely can affect the hair loss. I had no problems until I hit menopause and then the hair loss began.

bixa525: Are you getting hot flashes too? I know someone who got hot flashes after menopause and the way she solved that problem was giving blood. This is another reason why I believe iron might be a cause of hair loss problems in general. For you, it is possible that your body doesn't like accumulating so much iron all of a sudden since you no longer have your period.

Try giving blood as often as you can to see if it helps your symptoms.

Warren - A low DHEA could be an indication of hypoadrenia or low adrenal function. You might want to find out if you have adrenal fatigue and yes it can affect hair. I've got a section on it in the website below. One quick way to tell if you may have low adrenal function is to have your systolic blood pressure (top number) taken when lying down, and then immediately after in a standing position. If the systolic reading doesn't rise after standing up, you probably have hypoadrenia.

http://www.immortalhair.org/physiology.htm

bixa525 - I second Warren on the blood donation. The accumulation of iron at this stage increases oxidative stress and it very well may give you better hair. You'll also likely extend your life by doing so.

Thanks for the quick and informative response as usual CS. I went to this page and it seems I have a lot of adrenal fatigue symptoms as well! So perhaps I am a little hypothyroid and have adrenal issues...this shall be my research this week.

Wow that's interesting about giving blood. I was told this also helps keep you from getting colds and viruses so maybe I will have to give this a try and see if it helps. I also wonder about my adrenal function. They didn't test me for this when I had all my hormone tests and I guess this can cause hair loss too? I am going to try checking my blood pressure like you said. Boy there are so many things that can cause hair loss. Any other tips? I am looking for a good shampoo and conditoner, any good ones you would suggest? I have been using a prescription Ketoconazole and it is making my hair like straw.

You can also look into magnesium supplementation.

I use magnesium chloride and swear by it.

Here is a link http://www.puremagoil.com/dhea.htm

Here's info on adrenal fatigue

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Here are exploratory questions, and if you answer yes to any of these, you may have adrenals which are struggling (the STTM book has more questions in Chapter 5–see below):

1) Do you have a hard time falling asleep at night?
2) Do you wake up frequently during the night?
3) Do you have a hard time waking up in the morning early, or feeling refreshed?
4) Do bright lights bother you more than they should?
5) Do you startle easily due to noise?
6) When standing from sitting or from lying down, do you feel lightheaded or dizzy?
7) Do you take things too seriously, and are easily defensive?
8 ) Do you feel you don’t cope well with certain people or events in your life?

DISCOVERY STEP TWO: The following are self-tests to try if you suspect your adrenals are struggling:

TEST ONE:
Take and compare two blood pressure readings—one while lying down and one while standing. Rest for five minutes in recumbent position (lying down) before taking the reading. Stand up and immediately take the blood pressure again. If the blood pressure is lower after standing, suspect reduced adrenal gland function. The degree to which the blood pressure drops while standing is often proportionate to the degree of hypoadrenalism. (Normal adrenal function will elevate your BP on the standing reading in order to push blood to the brain.) It can be wise to do this test both in the morning and in the evening, since you can appear normal one time, and not another.
TEST TWO:
This is called the Pupil test and primarily tests your levels of aldosterone, another adrenal hormone. You need to be in a darkened room with a mirror. From the side (not the front), shine a bright light like a flashlight or penlight towards your pupils and hold it for about a minute. Carefully observe the pupil. With healthy adrenals (and specifically, healthy levels of aldosterone), your pupils will constrict, and will stay small the entire time you shine the light from the side. In adrenal fatigue, the pupil will get small, but within 30 seconds, it will soon enlarge again or obviously flutter in it’s attempt to stay constricted. Why does this occur? Because adrenal insufficiency can also result in low aldosterone, which causes a lack of proper amounts of sodium and an abundance of potassium. This imbalance causes the sphincter muscles of your eye to be weak and to dilate in response to light. Click here to see a video of fluctuating pupils, and thanks to Lydia for providing this.
TEST THREE:
Let someone shine a bright light your way. Even the above pupil test could have revealed this. Do you find yourself very sensitive and uncomfortable with the bright light? That could be a sign of adrenal fatigue. And this can also be true if you have searing headaches along with the sensitivity.
TEST FOUR:
You can determine your thyroid and adrenal status by following Dr. Rind with a temperature graph. You simply take your temp 3 times a day, starting three hours after you wake up, and every three hours after that, to equal three temps. (If you have eaten or exercised right before it’s time to take your temp, wait 20 more minutes.) Then average them for that day. Do this for AT LEAST 5 days. If your averaged temp is fluctuating from day to day more than .2 to .3, you need adrenal support. If it is fluctuating but overall low, you need more adrenal support and thyroid. If it is fluctuating but averaging 98.6, you just need adrenal support. If it is steady but low, you need more thyroid and adrenals are likely fine. (We note that mercury thermometers are the most accurate.)

For those already on cortisol, the above temperature test (comparing at LEAST 5 days of averages) is ideal to know if you are on enough. In other words, if each averaged temp is more than .2-.3 from each other, you are not on enough HC.

Funny DHEA and DHEA-S should come up. I'm sure it's old news but it seems they may be secretly plotting against our locks:

5-dihydrotestosterone is known to play a crucial part in the regulation of hair growth and in the development of androgenetic alopecia. 5-dihydrotestosterone is formed locally within the hair follicle from the systemic precursor testosterone by cutaneous steroid 5-reductase. Moreover, adrenal steroids such as dehydroepiandrosterone are converted to 5-dihydrotestosterone by isolated hair follicles, which may provide an additional source of intrafollicular 5-dihydrotestosterone levels. Elevated urinary dehydroepiandrosterone and serum dehydroepiandrosterone sulfate have been reported to be present in balding young men. These reports suggest that dehydroepiandrosterone sulfate may act as an important endocrine factor in the development of androgenetic alopecia. Hence the question arises whether the dehydroepiandrosterone sulfate can be metabolized within the hair follicles to yield dehydroepiandrosterone by the microsomal enzyme steroid sulfatase, and where steroid sulfatase might be localized. We therefore performed immunostaining for steroid sulfatase on human scalp biopsies as well as analysis of steroid sulfatase enzyme activity in defined compartments of human beard and occipital hair follicles ex vivo. Using both methods steroid sulfatase was primarily detected in the dermal papilla. Steroid sulfatase activity was inhibited by estrone-3-O-sulfamate, a specific inhibitor of steroid sulfatase, in a concentration-dependent way. Furthermore, we show that dermal papillae are able to utilize dehydroepiandrosterone sulfate to produce 5-dihydrotestosterone, which lends further support to the hypothesis that dehydroepiandrosterone sulfate contributes to androgenetic alopecia and that steroid sulfatase inhibitors could be novel drugs to treat androgen-dependent disorders of the hair follicle such as androgenetic alopecia or hirsutism.

http://www.nature.com/jid/journal/v117/n6/abs/5601298a.html


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And maybe you guys can help me make sense of this interconversion enzyme jazz:


Interconversion enzymes in androgenetic alopecia

Research studies in patients with androgen insensitivity syndromes and 5alpha - reductase type-2 deficiencies indicate that androgenetic alopecia is induced by activation of follicular androgen receptors by dihydrotestosterone (DHT), a potent stimulator of hair loss in the scalp. Although the level of DHT may be directly dependent on the activity of 5 -reductase, it is also obviously affected by both the supply of androgen precursors and the metabolism of DHT.

Androgen synthesis begins with cholesterol, which is converted to pregnenolone. Recent work has shown that on the scalp there are local differences in the amounts of steroid metabolizing enzymes that convert weak androgens to more potent androgens. This is important because the skin is an endocrine target tissue for androgen hormone action, similar to the ovaries, testes, and adrenal gland. It is known that weak and abundant precursor hormones such as dehydroepiandrosterone can metabolize to more potent androgens such as testosterone and dihydrotestosterone (DHT).

The enzymes that are responsible for synthesis of androgens are localized in the sebaceous glands and hair follicles of scalp skin. The skin is an active site of androgen metabolism where testosterone, androstenedione, and dehydro-epiandrosterone (DHEA) are metabolized extensively. That is because the skin has the potential to mediate androgen action without relying on elevated systemic levels of testosterone or DHT. Testosterone is the major precursor of DHT in men, but other weaker hormones, such as DHEA are the major precursors of DHT in women.

In the hair follicle, the principal pathways involved in conversion of weak androgens like DHEA to more potent androgens are through activity of the enzymes:

•3 beta - hydroxysteroid dehydrogenase (3 beta - HSD)
•17 beta - hydroxysteroid dehydrogenase (17 beta - HSD).
In most target organs testosterone can be further metabolized to DHT via the action of 5 -reductase.

Once formed, potent androgens, such as testosterone and DHT, can be removed by conversion back to the weaker 17-ketosteroids, or are metabolized via other enzymatic pathways, including aromatase, which converts androgens to estrogens, and 3 -hydroxysteroid dehydrogenase to form androsterone and androstanediol. The latter can be glucuronidated to form androgen conjugates that are more rapidly cleared from the circulation. Remarkably, some target tissues, such as the hair follicle, show enhanced androgen metabolism and androgen sensitivity.

The enzymes of the 17 beta - hydroxysteroid dehydrogenase (17 beta - HSD) gene family are responsible for a key step in the formation and degradation of androgens and estrogens: catalyzing the interconversion of 17-ketosteroids and their active 17 beta - hydroxysteroid counterparts. The enzymes of the 17 beta - HSD gene family are responsible for the interconversion of DHEA and estradiol, androstenedione and testosterone, estrone and 17 beta -estradiol, as well as of androstenedione and DHT. The reverse oxidative reaction inactivates the potent hydroxysteroids into ketosteroids with little biologic activity. Therefore 17 beta -HSD controls the last step in the formation of all androgens and all estrogens, assuming a key role in the intracellular concentration of all active sex steroids.

That 17 beta - HSDs are important biologically in testosterone production is corroborated by the fact that deficiency of 17 beta - HSD leads to a form of pseudohermaphroditism. There are at least eight distinct genes described with at least five 17 beta - HSD isoenzymes having individual cell specific expression, substrate specificity, regulation mechanisms, and reductive or oxidative catalytic activity.

•Type I 17 beta - HSD principally controls reduction of estrone to 1713-estradiol, and type II 17 beta- HSD controls the reverse oxidative sequence.
•Types III and V 17 beta - HSD reduce androstenedione to testosterone.
•Types II and IV 17 beta - HSD inactivate testosterone by oxidation to androstenedione.
Histochemically, 17 beta - HSD appears to be located primarily in the outer root sheath of anagen hairs, but appears to diminish in the anagen follicle with progressive baldness. Some studies show a marked decrease in the production of androstenediol from DHEA in the frontal scalp of balding men. Steroid sulfatase, which cleaves DHEA sulfate, the most abundant circulating steroid, to DHEA, has been noted in the dermal papillae of the occipital scalp hair follicle.

Metabolism of the weak androgen DHEA may play an important role in control of androgenetic alopecia. Some target tissues show enhanced androgen metabolism and androgen sensitivity. Circulating DHEA-S may be more rapidly metabolized to DHEA via steroid sulphatase. If increased 3 beta - HSD activity is present, DHEA may be more rapidly converted to androstenedione. Similarly, Androstenedione may be converted to testosterone if 17 beta - HSD activity is present. If target cells convert weak androgens at an accelerated pace, then there will be enhanced conversion of testosterone to DHT. Another reason for increased sensitivity of a target to androgens is believed to involve an increase in the number of androgen receptors.

3 beta - HSD catalyzes an essential step in the biosynthesis of all steroid hormones including mineralocorticoids (steroid hormones that are secreted by the adrenal cortex and regulate the balance of water and electrolytes in the body), glucocorticoids (A group of anti-inflammatory steroidlike compounds that are produced by the adrenal cortex, and are sex steroids). Two forms of the enzyme have been described in humans: type I has been recorded primarily in the placenta, skin, and breast and type II in the adrenals and gonads. 3 beta - HSD deficiency has been noted in 17 percent of women with signs of androgen excess. The sebaceous glands in balding skin have been shown to express increased 3 beta - HSD activity when compared to non-balding scalp areas.

3 alpha - HSDs work along with the 5 alpha /5 beta - reductases to convert steroid hormones into tetrahydrosteroids. These oxidoreductase transformations are important in the inactivation of androgens, progestins, and glucocorticoids in the liver and in the regulation of the amount of a given hormone that can bind to a steroid hormone receptor. Thus, NADH and/or NADPH-dependent 35alpha - HSD or 3 beta - HSD can regulate the amount of DHT that can bind to the androgen receptor by controlling interconversion to weak androgens. (Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are two important coenzymes found in cells. NADH is the reduced form and NAD+ is the oxidized form of NAD).


http://www.androgeneticalopecia.com/hair-loss-biology/hair-loss-interconversion-enzymes.shtml

"What does it all mean Basil?"

I believe the first article basically states that DHT is being produced on-site in the DP from DHEA via steroid sulfatase, which is different than the 5aR pathway we usually focus on. Does anyone know anything about STS inhibitors?

It seems the second article talks about beta-HSDs' role in the conversion of weaker hormones into more potent ones and vice versa. I tried reading it last night but had difficulty pulling valuable information from it.

I have to wonder why some dudes here have low DHEA levels. Hmmm... maybe it's because their DHEA is being converted into androgens/DHT and the body's not repleting the serum DHEA? Sounds plausible...

chore - Interesting study. In that abstract as well as some before it, there was mention of estrone inhibiting steroid sulfatase. I've tried some internal plant based estrones but no noticeable effect.

And for some years tried natural 17-beta-HSD inhibitors such as 7-HMR and other Enterolactone precursors.

I've searched in vain for a natural way to boost 3-alpha-HSD to counteract 3-beta-HSD.

I wonder if the bacteria in our skin influences the steroidal enzymes. I do know it does this in the GI-tract.

Lookin' like Ell Cranell might be a STS inhibitor:

Structure-activity relationships of 17α-derivatives of estradiol as inhibitors of steroid sulfatase

The steroid sulfatase or steryl sulfatase is a microsomal enzyme widely distributed in human tissues that catalyzes the hydrolysis of sulfated 3-hydroxy steroids to the corresponding free active 3-hydroxy steroids. Since androgens and estrogens may be synthesized inside the cancerous cells starting from dehydroepiandrosterone sulfate (DHEAS) and estrone sulfate (E1S) available in blood circulation, the use of therapeutic agents that inhibit steroid sulfatase activity may be a rewarding approach to the treatment of androgeno-sensitive and estrogenosensitive diseases. In the present study, we report the chemical synthesis and biological evaluation of a new family of steroid sulfatase inhibitors. The inhibitors were designed by adding an alkyl, a phenyl, a benzyl, or a benzyl substituted at position 17a of estradiol (E2), a C 18-steroid, and enzymatic assays were performed using the steroid sulfatase of homogenized JEG-3 cells or transfected in HEK-293 cells. We observed that a hydrophobic substituent induces powerful inhibition of steroid sulfatase while a hydrophilic one was weak. Although a hydrophobic group at the 17a-position increased the inhibitory activity, the steric factors contribute to the opposite effect. As exemplified by 17α-decyl-E2 and 17α-dodecyl-E2, a long flexible side chain prevents adequate fitting into the enzyme catalytic site, thus decreasing capacity to inhibit the steroid sulfatase activity. In the alkyl series, the best compromise between hydrophobicity and steric hindrance was obtained with the octyl group (IC50 = 440 nM), but judicious branching of side chain could improve this further. Benzyl substituted derivatives of estradiol were better inhibitors than alkyl analogues. Among the series of 17a-(benzyl substituted)-E2 derivatives studied, the 3'-bromobenzyl, 4'-tert-butylbenzyl, 4'-butylbenzyl, and 4'-benzyloxybenzyl groups provided the most potent inhibition of steroid sulfatase transformation of E1S into E1 (IC50 = 24, 28, 25, and 22 nM, respectively). As an example, the tert-butylbenzyl group increases the ability of the E2 nucleus to inhibit the steroid sulfatase by 3000-fold, and it also inhibits similarly the steroid sulfatase transformations of both natural substrates, E1S and DHEAS. Interestingly, the newly reported family of steroid sulfatase inhibitors acts by a reversible mechanism of action that is different from the irreversible mechanism of the known inhibitor estrone sulfamate (EMATE

http://cat.inist.fr/?aModele=afficheN&cpsidt=824785

JDP710,

How does this magnesium oil work? Do you spray it on your skin? How much do you use? I am taking an oral magnesium glycinate product that my bio dr. prescribed for me. I also take DHEA in a cream form. If I wanted to take this form of magnesium would I have to drop the dhea in the cream?

This place needs an edit button in a strange way. Think I misinterpreted that information in my Ell-Cranell post... may not be a STS inhibitor. My fault...

chore - Sorry, the only way to edit here is to copy your post, then "X" or delete it and then paste and edit/send.