Hypothyroidism (Cortisol, Prolactin And Adrenal Hyperactivity) Causes Balding

[Travis]

I beg to disagree a bit. Enoxolone is actually an indiscriminate inhibitor of 11b-HSD - i.e. it inhibits both type I and II. This leads to increase in cortisol levels due to decreased degradation, even though new synthesis is also inhibited. This is why enoxolone leads to high blood pressure in humans and it not used more often clinically. I considered it as a supplement years ago but its indiscriminate 11b-HSD activity convinced me not to do it. I have tried it myself and it does lead to excess mineralocorticoid symptoms including water retention and weight gain around the midsection.
Enoxolone - Wikipedia
"...The structure of glycyrrhetinic acid is similar to that of cortisone. Both molecules are flat and similar at position 3 and 11. This might be the basis for licorice's anti-inflammatory action.[citation needed] 3-β-D-(Monoglucuronyl)-18-β-glycyrrhetinic acid, a metabolite of glycyrrhetinic acid, inhibits the conversion of 'active' cortisol to 'inactive' cortisone in the kidneys.[6] This occurs via inhibition of the enzyme by inhibiting the enzyme 11-β-hydroxysteroid dehydrogenase.[citation needed] As a result, cortisol levels are high within the collecting duct of the kidney. Cortisol has intrinsic mineralocorticoid properties (that is, it acts like aldosterone and increases sodium reabsorption) that work on ENaC channels in the collecting duct.[citation needed]Hypertension develops due to this mechanism of sodium retention. People often have high blood pressure with a low renin and low aldosterone blood level.[citation needed] The increased amounts of cortisol binds to the unprotected, unspecific mineralocorticoid receptors and induce sodium and fluid retention, hypokalaemia, high blood pressure and inhibition of the renin-angiotensin-aldosterone system. Therefore, licorice should not be given to patients with a known history of hypertension in doses sufficient to inhibit 11-β-hydroxysteroid dehydrogenase.[7]"

What is implied is that it should be quite safe topically. The kidneys of course have the 11β-HSD₂ working in the opposite direction, so taking enoxolone—or its all natural glycone found in licorice—certain can cause extreme mineralocorticoid effects due to excessive cortisol. I am even fairly certain that this has killed people, as has other natural mineralocorticoid-active molecules like digoxin, oubain, and solanine.

But topically, I think you could expect local inhibition of cortisol synthesis. There are better drugs out there, that work in a more direct way, but this has been tested topically on rats and they all had survived and the all had increased hair growth—proving that cortisol was being inhibited and had not increased, as would occur if the skin were to contained 11β-HSD₂ and not 11β-HSD₁. Although spironolactone would be a more direct approach, topically, it is more expensive and difficult to acquire.

Saumendu, D. "Hair growth stimulating effect and phytochemical evaluation of hydro-alcoholic extract of Glycyrrhiza glabra." Global Journal of Research on Medicinal Plants & Indigenous Medicine (2014)​

 

[haidut]

What is implied is that it should be quite safe topically. The kidneys of course have the 11β-HSD₂ working in the opposite direction, so taking enoxolone—or its all natural glycone found in licorice—certain can cause extreme mineralocorticoid effects due to excessive cortisol. I am even fairly certain that this has killed people, as has other natural mineralocorticoid-active molecules like digoxin, oubain, and solanine.

But topically, I think you could expect local inhibition of cortisol synthesis. There are better drugs out there, that work in a more direct way, but this has been tested topically on rats and they all had survived and the all had increased hair growth—proving that cortisol was being inhibited and had not increased, as would occur if the skin were to contained 11β-HSD₂ and not 11β-HSD₁. Although spironolactone would be a more direct approach, topically, it is more expensive and difficult to acquire.

Saumendu, D. "Hair growth stimulating effect and phytochemical evaluation of hydro-alcoholic extract of Glycyrrhiza glabra." Global Journal of Research on Medicinal Plants & Indigenous Medicine (2014)​

Concur. What about RU486 or even progesterone, both of which block GR? Maybe even combine exonolone and one of these two? What about topical emodin, which is a selective 11b-HSD1 inhibitor?

 

[Travis]

Concur. What about RU486 or even progesterone, both of which block GR? Maybe even combine exonolone and one of these two? What about topical emodin, which is a selective 11b-HSD1 inhibitor?

Emodin is nice, cheap, unpatented, prevalent, and it works, but if you look at the binding affinities I think you'd note that enoxolone binds far stronger than anything else. As far as I can tell, enoxolone and its parent compound are the only 11β-HSD₁∶₂ inhibitors that bind so well as to be dangerous.

 

[haidut]

Emodin is nice, cheap, unpatented, prevalent, and it works, but if you look at the binding affinities I think you'd note that enoxolone binds far stronger than anything else. As far as I can tell, enoxolone and its parent compound are the only 11β-HSD₁∶₂ inhibitors that bind so well as to be dangerous.

What is the IC50/Km of enoxolone for 11b-HSD?

 

[Mauritio]

I wrote Dr. Peat and he was kind to reply to a few questions. Well, actually, he didn't really answer each of my questions directly, but he did offer a lot of great information. I asked him if it was ok to share his answer on the forum, and he said he didn't mind. My words are in black; Ray's is in dark blue and the references he gave are in light blue.

Hello Dr. Peat,

My name is Brandon. I recieved this email address in the forum when requesting a way to contact you. If you don't mind, I'd like to get your perspective on the following questions concerning the pattern of common baldness in adult males:

1. What is the basis for the onset of common pattern baldness in adult males, starting at the temples and vertex and developing into the virtually symmetrical horseshoe shape?

2. Is the development of this precise pattern a sign of a systemic problem?

3. How do you make sense of the association between pattern baldness and elevated prolactin and cortisol if women also experience elevations in these hormones, but don't show this pattern of baldness?

I listened to the KMUD episode on hair loss and inflammation you were on, where you mentioned that prolactin and cortisol are elevated in people with baldness (I'm assuming you were referring to the common pattern baldness), but I didn't hear an explanation about how this elevation is related to the actual pattern of baldness seen in males.

Women are more strongly protected than men by progesterone against the stress hormones. Prostaglandins, which are one of the products of estrogen-related mast cells, are increased by the accumulation of polyunsaturated fats with aging, and correspond roughly to the health problems, such as the “metabolic syndrome,” that are associated in men with baldness. Testosterone has some of the protective effects of progesterone, except that with the gradual accumulation of the PUFA, it tends to be turned into estrogen, activating cortisol, prostaglandins, mast cells, and prolactin.

J Am Anim Hosp Assoc. 2015 Mar-Apr;51(2):136-42.
Canine alopecia secondary to human topical hormone replacement therapy in six
dogs.
Berger DJ(1), Lewis TP, Schick AE, Miller RI, Loeffler DG.
(1)From the Iowa State University College of Veterinary Medicine, Ames, IA
(D.B.); Dermatology for Animals (T.L., A.S., R.M.); and DVM Pathology Associates
(D.L.).

Dermatologica Sinica Volume 34, Issue 1, March 2016, Pages 10–13
Assessment of semen quality in patients with androgenetic alopecia in an infertility clinic
Emre Sinan Güngör, Şule Güngör, , , Ali Galip Zebitay. . . .
Redirecting

Urolithiasis. 2016 Oct;44(5):409-13.
Relation of urinary stone disease with androgenetic alopecia and serum
testosterone levels.
Polat EC(1), Ozcan L(2), Otunctemur A(3), Ozbek E(3).
(1)Department of Urology, Okmeydani Training and Research Hospital, Sisli, 34384,
Istanbul, Turkey. [email protected]. (2)Department of Urology, Derince
Training and Research Hospital, Kocaeli, İzmit, Turkey. (3)Department of Urology,
Okmeydani Training and Research Hospital, Sisli, 34384, Istanbul, Turkey.

Am J Phys Anthropol. 1992 May;88(1):59-67.
Relations between sex hormone level and characters of hair and skin in healthy
young men.
Knussmann R(1), Christiansen K, Kannmacher J.
(1)Institut für Humanbiologie, University of Hamburg, Germany.

Singapore Med J. 2010 Dec;51(12):931-6.
The association of insulin resistance and metabolic syndrome in early
androgenetic alopecia.
Acibucu F(1), Kayatas M, Candan F.
(1)Department of Endocrinology and Metabolism, Faculty of Medicine, Cumhuriyet
University, Sivas 58140, Turkey. [email protected]

J Drugs Dermatol. 2016 Aug 1;15(8):1001-4.
Stress and the Hair Growth Cycle: Cortisol-Induced Hair Growth Disruption.
Thom E.

J Cutan Pathol. 1975;2(2):58-70.
Male pattern alopecia a histopathologic and histochemical study.
Lattanand A, Johnson WC.

J Cutan Pathol. 2014 Apr;41(4):364-9.
A prostaglandin D-synthase-positive mast cell gradient characterizes scalp
patterning.
Larson AR(1), Zhan Q, Johnson E, Fragoso AC, Wan M, Murphy GF.

Thank you so much for your reply. Do you have a sense of why the pattern of baldness is the way it is (horseshoe)?

I think the pattern is just an expression of the interacting gradients that shape all development. In the skin, pheromones and electrical fields are among the factors that affect sweat, oil, hair, fibroblasts, inflammatory, and pigment cells. Each type of cell responds to changing gradients in its own way.

Can somone explain this sentence to me ? Its quoted from :
Relations between sex hormone level and characters of hair and skin in healthy young men.

"... and the proportion of free to total testosterone. The disposition to balding also correlates positively with the latter ratio."
does this mean the more free (and less total) testosterone somone has the more likely he is to be balding?

p.s. :sorry for the big letters

 

[LCohen]

Any way to inhibit Androstenedione ? It's easily aromatizable.

 

[benaoao]

oh well, I just dropped a long post on the other thread before reading this one. I'm sure the hypothyroid/Hydroxysteroid dehydrogenase activity leading to an imbalanced DHT/3bDiol ratio has been debated here...

 

[Hiwatt]

I don't take any supplements aside from my egg shell calcium.

I rarely drink water because I'm rarely thirsty. I suppose fruit and bone broth give me a decent amount. I don't ever really just have a glass of water though; a liter a week maybe. I find it makes me cold and urinate too frequently.

I just looked up a simple pho broth on-line. Bake bones and an onion, add to water, add spices, simmer overnight. Voila. Serve with a little beef and rice noodles, and a glass of milk.

I don't have an opinion on oregano oil and energin. My digestive issues resolved themselves when I started eating a couple raw carrots a day and moved to an otherwise easy-to-digest diet. No magic involved; just let my body do its thing.

Save your egg shells, rinse them out, boil them to remove the remaining film, bake the egg shells to dry them and kill any bacteria that might remain. Run them through a coffee grinder and store in a mason jar. I suppose if milk, cheese, and leafy greens are staples you'll get sufficient calcium. The other thing to consider is the amount of phosphate you're getting as it directly stimulates parathyroid. Those meat+potato meals are likely a massive phosphate load.
Disorders Involving Calcium, Phosphorus, and Magnesium
High phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro. - PubMed - NCBI

I eat oysters a couple nights a week. I make various dishes; been on a thai green curry kick as of late. I just think of foods I enjoy and find recipes to make them myself, since I don't much trust what restaurants use. I wish I knew what to tell you regarding liver. I don't think there's any food that gives as immediate and strong a benefit as I get from liver, especially during the summer when my retina is constantly stimulated.

It's good you're avoiding a hypocaloric diet. If that means you have to eat potatoes, it's probably better than not getting enough food. I would just advise cooking them well and eating with saturated fat to make sure they properly digest and, again, consume with a good source of calcium.

I was wondering if canned oysters are acceptable and if there is a particular brand that people know of?

Thank You

 

[SOMO]

Any way to inhibit Androstenedione ? It's easily aromatizable.

How is Androstenedione more subject to Aromatase than Testosterone?

 

[LCohen]

How is Androstenedione more subject to Aromatase than Testosterone?

Who said it's more subject ?

Androstenedione can turn into testosterone either worst estrogen form called estrone. Even for women estrone is sh*t. While estradiol and estriol more innocent.

Testosterone -on the other hand- can be converted into a strong androgen. (DHT) either to estrogen.

The main subject can be aromatase enzyme which responsible for androgen to estrogen conversion..

 

[unicorn]

Great info. Now that we have established this, I think what interests me the most is how does hair REgrow? Is it possible? Do they need some sort of stimulation to start again? Is there no chance of it happening and we need to go for hair transplants?

I am fortunate enough to have found the teachings of RP et al., and managed to save 80% of my hair. A transplant would take me back to 100%. However, I always wanted to do it by myself

 

[Mauritio]

Great info. Now that we have established this, I think what interests me the most is how does hair REgrow? Is it possible? Do they need some sort of stimulation to start again? Is there no chance of it happening and we need to go for hair transplants?

I am fortunate enough to have found the teachings of RP et al., and managed to save 80% of my hair. A transplant would take me back to 100%. However, I always wanted to do it by myself

I have regrown a lot of hair and it's still there for like 3 or 4 years or so.
So I did my own experiments and now im proud to say that I am almost 100 percent sure that hair can grow back because I have seen it on self.
The bad part is that my old hair still falls out when I get too high stress hormones but my hairline is slowly recovering.
I do Tom hagerty s scalp exercises ,which is an alternating contraction of certain muscles on the scalp ,which ultimately brings nutrient and oxygen to the hair.
Its more like the scalp massage but without hurting the scalp.

 

[johnwester130]

Spiro does not reduce cortisol?

In any case, the levels of most steroid hormones, including testosterone and cortisol, are usually unchanged by spironolactone in humans, which may in part be related to compensatory upregulation of their synthesis.[113][131][190] The weak steroidogenesis inhibition of spironolactone might contribute to its antiandrogenic efficacy to some degree and may explain its side effect of menstrual irregularities in women.[113][114] However, its androgen synthesis inhibition is probably clinically insignificant.[54]

Spironolactone has been found in some studies to increase levels of estradiol, an estrogen, although many other studies have found no changes in estradiol levels.[113][131] The mechanism of how spironolactone increases estradiol levels is unclear, but it may involve inhibition of the inactivation of estradiol into estrone and enhancement of the peripheral conversion of testosterone into estradiol.[191][192] It is notable that spironolactone has been found in vitro to act as a weak inhibitor of 17β-hydroxysteroid dehydrogenase 2, an enzyme that is involved in the conversion of estradiol into estrone.[193][194] Increased levels of estradiol with spironolactone may be involved in its preservation of bone density and in its side effects such as breast tenderness, breast enlargement, and gynecomastia in women and men.[191][195][196]

In response to the antimineralocorticoid activity spironolactone, and in an attempt to maintain homeostasis, the body increases aldosterone production in the adrenal cortex.[197][198][199] Some studies have found that levels of cortisol, a glucocorticoid hormone that is also produced in the adrenal cortex, are increased as well.[198][199][200] However, other clinical studies have found no change in cortisol levels with spironolactone,[138][201][85][202] and those that have found increases often have observed only small changes.

 

[johnwester130]

Interesting - topical administration of acetazolamide anyone?

many carbonic anhydrase inhibitors are sold in liquid form,

for example, dorzolamide

topical dorzolamide anyone?