Evidence That Cortisol Really Does Cause Hair Loss

[Koveras]

I am getting the impression that anything which leads to reduced blood flow, including prostaglandin D₂, plays a role. I think cortisol is necessary to explain the hormonal effects, interferon-γ and prostaglandins to explain the immunogenic effects, vitamin D accounting for sun, and other forms of reduced blood flow to explain the rest. If prostaglandin D₂ can be linked to arterial constriction—and it certainly can, as shown below—then it could perhaps be viewed as acting ultimately in this way: the final downstream process. Seeing ischemia and reduced blood flow as the ultimate cause actually makes nearly all popular explanations synergistic, the apparent competition between them perhaps being merely a lack of understanding.

'Prostaglandin D₂ is a powerful antiaggregatory agent and contracts various types of smooth muscle preparations, including isolated canine and bovine pulmonary vessels.' ―Cassin

'Prostaglandin D₂ was originally described by Nugteren and Hazelhof (17) as being biologically inactive. However, in 1975, Hamberg et al. (9) described vasopressor responses to PGD₂ as well as bronchoconstrictor activity in experiments on guinea pigs. Other studies (11, 12) have provided evidence of smooth muscle stimulatory activity of PGD₂ in a variety of species. In 1976, Jones (12) demonstrated pressor activity of PGD₂ in sheep. Additional data have been accumulated to show that PGD₂ increases canine pulmonary vascular resistance (14, 25) and contracts isolated bovine and canine intrapulmonary vessels (8).' ―Cassin​

The Cassin experiment had only measured bronchial resistance, but he cites Hamberg and Jones as having shown pressor effects in arteries. The article by Jones—'Cardiovascular actions of prostaglandins D and E in the sheep: evidence for two distinct receptors'— stands out; not only because it includes the phrase 'in the sheep,' but because it apparently has the hard data which demonstrates this.

Hamberg, Mats. "Prostaglandin endoperoxides IV. Effects on smooth muscle." Life sciences (1975)
Cassin, S. "Effects of prostaglandin D2 on perinatal circulation." American Journal of Physiology-Heart and Circulatory Physiology (1981)
Jones, R. L. "Cardiovascular actions of prostaglandins D and E in the sheep: evidence for two distinct receptors." Advances in prostaglandin and thromboxane research (1976).​

I have an as of yet unpublished theory (Koveras, 2018) that one of the mechanisms prolactin contributes to hair loss is from being cleaved to vasoinhibins.

"Prolactin acquires antiangiogenic properties after undergoing proteolytic cleavage to vasoinhibins, a family of PRL fragments (including 16 kDa PRL) with potent antiangiogenic, vasoconstrictive, and antivasopermeability effects."​

I imagine factors which upregulate Cathepsin D, MMPs, and BMP-1 (and thus contribute to this cleavage) will contribute to hair loss.

Clapp, C., Thebault, S., Macotela, Y., Moreno-Carranza, B., Triebel, J., & Martinez de la Escalera, G. (2015). Regulation of blood vessels by prolactin and vasoinhibins. Adv Exp Med Biol, 846, 83-95. doi:10.1007/978-3-319-12114-7_4​

 

[Travis]

I have an as of yet unpublished theory (Koveras, 2018) that one of the mechanisms prolactin contributes to hair loss is from being cleaved to vasoinhibins.

"Prolactin acquires antiangiogenic properties after undergoing proteolytic cleavage to vasoinhibins, a family of PRL fragments (including 16 kDa PRL) with potent antiangiogenic, vasoconstrictive, and antivasopermeability effects."​

I imagine factors which upregulate Cathepsin D, MMPs, and BMP-1 (and thus contribute to this cleavage) will contribute to hair loss.

Clapp, C., Thebault, S., Macotela, Y., Moreno-Carranza, B., Triebel, J., & Martinez de la Escalera, G. (2015). Regulation of blood vessels by prolactin and vasoinhibins. Adv Exp Med Biol, 846, 83-95. doi:10.1007/978-3-319-12114-7_4​

View attachment 7927

That is interesting. In this article here,* biological chemists had created a few different prolactin analogues in an attempt to create a prolactin inhibitor. They had noticed strong binding with small N‐terminal deletions accompanied by a reduction in biological activity. Mutations at glycine¹²⁹ abrogated binding to one receptor, but not the other; but this is well within the vasoinhibin fragment of ~155 amino acids.

Vasoinhibins prevent calcium influx, and yet their receptor has not been found. Due to these facts and the prolactin analogue binding data, you might assume that perhaps it becomes an antagonist of one of the prolactin receptors upon enzymatic cleavage. But unfortunately, all of the prolactin analogues used in the study* were essentially full‐length prolactin.

Is calcium flux necessary to activate muscles in all cases? Both prolactin and the prostaglandin D₂ regulate calcium flux, and they both cause muscle contraction. It would be interesting to see where exactly the G protein‐coupled prostaglandin D₂ receptors are, or how they are localized within the body.. .

[*] Jomain, Jean-Baptiste. "Structural and thermodynamic bases for the design of pure prolactin receptor antagonists X-ray structure of Del1-9-G129R-hPRL." Journal of Biological Chemistry (2007)​

 

[Travis]

Ignore that thought. It appears as though prolactin may need its entire 200+ amino acids for efficient binding, as it binds between two receptor halves. A loss of the C‐terminal fragment would likely distort the entire protein hormone.

'Despite their low degree of sequence similarity, the 3D structures of the ligand binding domains of GHR and PRLR appear to be almost superimposable.' ―Goffin​

​

'Based on their structural features, PRLR and GHR were initially believed to form a distinct receptor family (1). However, further sequence comparisons among newly-identified membrane receptors led to the identification of a new family of receptors sharing most of the characteristics described earlier for PRLR and GHR (pairs of cysteines, WS motif, Box 1, Box 2) (1,9). Termed Class-1 cytokine receptors, this new superfamily includes receptors for several interleukins...' ―Goffin​

And if were to bind, it would still likely work: This is because the working end is the N‐terminal fragment interacting with the WSXWS domain, a conserved region for all cytokine receptors. Receptor binding induces a conformational change of this domain, as determined by circular dichroism at ~220·nm, the emission frequency of tryptophan in proteins.

'The D2 domain of PRLR contains an interesting structural feature, namely a highly conserved Trp-Ser-Xaa-Trp-Ser motif, here referred to as the WS motif. This motif—or conservative variations thereof—is observed in all cytokine receptors.' ―Dagil

'The WS motif, and indeed the entire Trp/Arg ladder, is positioned opposite the PRL binding loop and the receptor dimerization interface. However, mutations of the WS motif to all-alanine in rPRLR decreased binding affinity for ovine PRL 23-fold.' ―Dagil​

Although the N‐terminal region is certainly the most important, both halves participate in binding through ~9 salt bridge interactions consisting of positively charged lysine⁺ and arginine⁺ groups interacting with negatively charged aspartate⁻ and glutamate⁻ side‐chains. The salt bridge just an ionic bond, yet is higher in energy that 'H‐bonds' (which aren't really bonds.) I think most receptor〜ligand interactions of the protein·protein type rely on salt bridge interactions.

'An exhaustive mutation study of 19 individual single amino acid substitutions of each of the five residues of the WS motif in the erythropoietin receptor (EPOR) revealed an extremely limited tolerance toward changes (Hilton et al., 1996).' ―Dagil​

This motif is conserved throughout all cytokine receptors, so it's important. Upon binding the tryptophans align:

'In atomic detail, the WS motif acts as a molecular switch controlling whether the receptor is in the off-state or in the on-state.' ―Dagil​

​

'The structures of the PRL-bound state of PRLR-ECD suggested that the T-stack of the unbound state rearranges to form the Trp/Arg ladder in the bound state. The Trp exciton coupling was used to follow hormone binding by comparing the far-UV CD spectra of unbound and hPRL-bound hPRLR-ECD (Figure 4A). This was done by subtracting the CD spectrum of the sum of the spectra of PRL and hPRLR-ECD from that of the spectrum of the hPRL:hPRLR-ECD complex. A significant loss in signal intensity was seen at 228 nm. A loss of the Trp-Trp π-π∗ exciton coupling upon PRL binding would expectedly lead to a concomitant loss of an opposite signed feature at 216 nm, which is not observed here. However, because formation of the complex between PRLR-ECD and PRL leads to increased β-sheet and α-helix stabilization, this will mask the signature at 216 nm. Thus, it appears that PRL binding to PRLR-ECD leads to a conformational change involving the WS motif as suggested from the structures.' ―Dagil​

So this is why changes in the N‐terminal led to reduced activity with no significant reduction in binding capacity. I would think that large modifications in the C‐terminal, such as what occurs in the formation of vasoinhibins, would lead to the converse: a decreased binding affinity with no loss of activity should binding actually occur. Since this doesn't seem to fit the characteristics of vasoinhibins, I'd think that they work on a separate receptor. Since the prolactin receptor is a member of the cytokine superfamily, you could be tempted to think that the unidentified target of vasoinhibins could be a cytokine receptor.. .

Somers, William, et al. "The X-ray structure of a growth hormone–prolactin receptor complex." Nature (1994)
Goffin, Vincent, and Paul A. Kelly. "The prolactin/growth hormone receptor family: structure/function relationships." Journal of mammary gland biology and neoplasia (1997)
Dagil, Robert, et al. "The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor." Structure (2012)​

 

[mayweatherking]

scalp itch 100% comes from whether your digestive system is working or not, which is what travis is saying about cortisol being high, the only time i get "scalp itch" is when there is backlog in my digestive system, if i am completely cleared up, the scalp itch disappears completely, pregnenlone gets the digestive system moving, i think once your pregnenlone is at a normal level, and vitamin D is good, i think you would be be all right

 

[eddiem991]

I am getting the impression that anything which leads to reduced blood flow, including prostaglandin D₂, plays a role. I think cortisol is necessary to explain the hormonal effects, interferon-γ and prostaglandins to explain the immunogenic effects, vitamin D accounting for sun, and other forms of reduced blood flow to explain the rest. If prostaglandin D₂ can be linked to arterial constriction—and it certainly can, as shown below—then it could perhaps be viewed as acting ultimately in this way: the final downstream process. Seeing ischemia and reduced blood flow as the ultimate cause actually makes nearly all popular explanations synergistic, the apparent competition between them perhaps being merely a lack of understanding.

'Prostaglandin D₂ is a powerful antiaggregatory agent and contracts various types of smooth muscle preparations, including isolated canine and bovine pulmonary vessels.' ―Cassin

'Prostaglandin D₂ was originally described by Nugteren and Hazelhof (17) as being biologically inactive. However, in 1975, Hamberg et al. (9) described vasopressor responses to PGD₂ as well as bronchoconstrictor activity in experiments on guinea pigs. Other studies (11, 12) have provided evidence of smooth muscle stimulatory activity of PGD₂ in a variety of species. In 1976, Jones (12) demonstrated pressor activity of PGD₂ in sheep. Additional data have been accumulated to show that PGD₂ increases canine pulmonary vascular resistance (14, 25) and contracts isolated bovine and canine intrapulmonary vessels (8).' ―Cassin​

The Cassin experiment had only measured bronchial resistance, but he cites Hamberg and Jones as having shown pressor effects in arteries. The article by Jones—'Cardiovascular actions of prostaglandins D and E in the sheep: evidence for two distinct receptors'— stands out; not only because it includes the phrase 'in the sheep,' but because it apparently has the hard data which demonstrates this.

Hamberg, Mats. "Prostaglandin endoperoxides IV. Effects on smooth muscle." Life sciences (1975)
Cassin, S. "Effects of prostaglandin D2 on perinatal circulation." American Journal of Physiology-Heart and Circulatory Physiology (1981)
Jones, R. L. "Cardiovascular actions of prostaglandins D and E in the sheep: evidence for two distinct receptors." Advances in prostaglandin and thromboxane research (1976).​

Elevated prostaglandin D seems to be the final stage of a bald area, inhibiting any hair growing back. It's intressting how calcium is concentrated in the bald scalp. I read about some drug preventing potassium loss regrowing hair, can't remember it's name though.

 

[xetawaves]

Why is it so hard to grow hair from skin full of hair follicles lol I do feel like 2018 is going to be a great year for hair loss treatments/research though. People are losing their hair earlier than past generations and everyone is starting to realize it's becoming a real problem.

 

[johnwester130]

Ignore that thought. It appears as though prolactin may need its entire 200+ amino acids for efficient binding, as it binds between two receptor halves. A loss of the C‐terminal fragment would likely distort the entire protein hormone.

'Despite their low degree of sequence similarity, the 3D structures of the ligand binding domains of GHR and PRLR appear to be almost superimposable.' ―Goffin​

View attachment 7928
​

'Based on their structural features, PRLR and GHR were initially believed to form a distinct receptor family (1). However, further sequence comparisons among newly-identified membrane receptors led to the identification of a new family of receptors sharing most of the characteristics described earlier for PRLR and GHR (pairs of cysteines, WS motif, Box 1, Box 2) (1,9). Termed Class-1 cytokine receptors, this new superfamily includes receptors for several interleukins...' ―Goffin​

And if were to bind, it would still likely work: This is because the working end is the N‐terminal fragment interacting with the WSXWS domain, a conserved region for all cytokine receptors. Receptor binding induces a conformational change of this domain, as determined by circular dichroism at ~220·nm, the emission frequency of tryptophan in proteins.

'The D2 domain of PRLR contains an interesting structural feature, namely a highly conserved Trp-Ser-Xaa-Trp-Ser motif, here referred to as the WS motif. This motif—or conservative variations thereof—is observed in all cytokine receptors.' ―Dagil

'The WS motif, and indeed the entire Trp/Arg ladder, is positioned opposite the PRL binding loop and the receptor dimerization interface. However, mutations of the WS motif to all-alanine in rPRLR decreased binding affinity for ovine PRL 23-fold.' ―Dagil​

Although the N‐terminal region is certainly the most important, both halves participate in binding through ~9 salt bridge interactions consisting of positively charged lysine⁺ and arginine⁺ groups interacting with negatively charged aspartate⁻ and glutamate⁻ side‐chains. The salt bridge just an ionic bond, yet is higher in energy that 'H‐bonds' (which aren't really bonds.) I think most receptor〜ligand interactions of the protein·protein type rely on salt bridge interactions.

'An exhaustive mutation study of 19 individual single amino acid substitutions of each of the five residues of the WS motif in the erythropoietin receptor (EPOR) revealed an extremely limited tolerance toward changes (Hilton et al., 1996).' ―Dagil​

This motif is conserved throughout all cytokine receptors, so it's important. Upon binding the tryptophans align:

'In atomic detail, the WS motif acts as a molecular switch controlling whether the receptor is in the off-state or in the on-state.' ―Dagil​

View attachment 7929​

'The structures of the PRL-bound state of PRLR-ECD suggested that the T-stack of the unbound state rearranges to form the Trp/Arg ladder in the bound state. The Trp exciton coupling was used to follow hormone binding by comparing the far-UV CD spectra of unbound and hPRL-bound hPRLR-ECD (Figure 4A). This was done by subtracting the CD spectrum of the sum of the spectra of PRL and hPRLR-ECD from that of the spectrum of the hPRL:hPRLR-ECD complex. A significant loss in signal intensity was seen at 228 nm. A loss of the Trp-Trp π-π∗ exciton coupling upon PRL binding would expectedly lead to a concomitant loss of an opposite signed feature at 216 nm, which is not observed here. However, because formation of the complex between PRLR-ECD and PRL leads to increased β-sheet and α-helix stabilization, this will mask the signature at 216 nm. Thus, it appears that PRL binding to PRLR-ECD leads to a conformational change involving the WS motif as suggested from the structures.' ―Dagil​

So this is why changes in the N‐terminal led to reduced activity with no significant reduction in binding capacity. I would think that large modifications in the C‐terminal, such as what occurs in the formation of vasoinhibins, would lead to the converse: a decreased binding affinity with no loss of activity should binding actually occur. Since this doesn't seem to fit the characteristics of vasoinhibins, I'd think that they work on a separate receptor. Since the prolactin receptor is a member of the cytokine superfamily, you could be tempted to think that the unidentified target of vasoinhibins could be a cytokine receptor.. .

Somers, William, et al. "The X-ray structure of a growth hormone–prolactin receptor complex." Nature (1994)
Goffin, Vincent, and Paul A. Kelly. "The prolactin/growth hormone receptor family: structure/function relationships." Journal of mammary gland biology and neoplasia (1997)
Dagil, Robert, et al. "The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation: insight from structures of the prolactin receptor." Structure (2012)​

could selenium work ?

Influence of selenium on mast cell mediator release. - PubMed - NCBI

 

[Travis]

could selenium work ?

Influence of selenium on mast cell mediator release. - PubMed - NCBI

Since the selenite ion decreased prostaglandin D₂ release by mast cells—by about half at a ~3·μM concentration—you'd be tempted to say 'yes' . . . especially considering the testimonial on the previous page. However! the biochemical paradigm I'm under would require there to be mast cells in the skin for this to have a mechanistic explanation. But a quick search indicates that there are in fact mast cells normally in the skin at roughly 4.7% by mass, making sodium selenite a seemingly effective addition to shampoo.

The author says this, for those interested in the chemical mechanism:

'The mechanism by which selenium modifies mast cell mediator release is likely mediated, at least for histamine and prostaglandin D₂, by regulation of redox-sensitive transcription factors, which affects production of cytokines and prostaglandins [16].' ―Safaralizadeh​

Which is interesting. I have read two articles on these redox-sensitive transcription factors, and they certainly do exist. These are dependent on disulfide bridges, with either electrons or H₂O₂ able to break the sulfur–sulfur bonds. This would naturally lead to a profound change in the protein's entire shape, and a very convincing and intuitive way in which a cell could sense the external milieu on a molecular level.

From Safaralizadeh's citation [16] and we have this:

'The selenoenzyme thioredoxin reductase affects the redox regulation of several key enzymes, transcription factors and receptors, including ribonucleotide reductase, glucocorticoid receptors, anti-inflammatory protein AP-1, and NF-κB, which binds to DNA and activates expression of genes encoding proteins involved in immune response (cytokines, adhesion molecules) [116–119]' ―Wintergerst​

So depending on the characteristics of this selenoenzyme, and what's lurking in citations 116–119, perhaps the selenide ion (Se²⁻) would work in addition to the selenite (SeO₃²⁻) ion used in you article you had found. These are different species with similar names.

Nice find. I'll be sure to read some articles on how this purportedly works. If I stumble across any interesting clinical data and/or testimonials I'll be sure to post them.

 

[eddiem991]

could selenium work ?

Influence of selenium on mast cell mediator release. - PubMed - NCBI

selenium disulphide is a prostaglandin D2 antagonist.

 

[DaveFoster]

So baldness is basically heart disease ?

Pauling Therapy Case Summaries - hair regrowth is mentioned

Depression has been associated with hair loss, and cortisol contributes to both pathologies (and heart disease) in males:

"...MDD [major depressive disorder] and ND [non-depressive] individuals exhibited similar baseline and stress cortisol levels, but MDD patients had much higher cortisol levels during the recovery period than their ND counterparts."

SOURCE: Depression and cortisol responses to psychological stress: a meta-analysis. - PubMed - NCBI

"Cushing's syndrome is a consequence of primary or, more commonly, secondary oversecretion of cortisol. Cardiovascular disease is the major cause of morbidity and mortality in Cushing's syndrome...the cardiovascular consequences of cortisol excess are protean and include, inter alia, elevation of blood pressure, truncal obesity, hyperinsulinemia, hyperglycemia, insulin resistance, and dyslipidemia."​

SOURCE: Cardiovascular Consequences of Cortisol Excess​

"Measurements of serum androgens, testosterone, dihydroepiandrosterone sulphate (DHEA), and free testosterone levels have failed to demonstrate a reproducible difference between cases and controls [for androgenic alopecia] (51). A study that assessed different hormonal levels in MAA and age-matched controls measured elevated levels of cortisol and androstenedione in those experiencing MAA [male androgenic alopecia] (52). This study further suggests a broad range of hormones may influence androgenetic alopecia. Even though scalp hair loss and hirsutism are essential features of hyperandrogenism in women, several investigations failed to demonstrate raised androgen levels in women (53). Therefore it is suggested that normal levels of androgens are sufficient to cause hair loss in genetically susceptible individuals."​

SOURCE: Male Androgenetic Alopecia - Endotext - NCBI Bookshelf​

Stress obviously can trigger depressive symptoms, and it's well known that stress can cause alopecia areata, but there's this disconnect that treats MPB as a divergent condition even in spite of the evidence that testosterone has gabergic properties and increases stress tolerance significantly (similar to progesterone).

Therefore, to support "androgenic alopecia," the syndrome has to be divorced from the context of stress in spite of the observation that stress increases the activity of the 5-ar enzyme:

DHT Production Depends On Stress

Stress (including cortisol) can acutely raise in tandem with DHEA:

"...the enhancement of plasma levels of DHEAs were dependent on cortisol, as shown by the close correlation between both hormones..."​

SOURCE: [Study of the stress response: role of anxiety, cortisol and DHEAs]. - PubMed - NCBI​

The DHEA elevations in response to acute stress act as a protective adaptation.

Further, estrogen has a masculinizing effect (similar to testosterone):

"The masculinization of these cells is independent of AR but can be induced by either testosterone or estrogen, indicating a role for aromatase in sexual differentiation of these neurons."​

SOURCE: [Study of the stress response: role of anxiety, cortisol and DHEAs]. - PubMed - NCBI​

It's also mentioned that serotonin released from platelets (induced by gut irritation or psychological stress) can increase the aggressive response in the context of hyperandrogenism with elevated estrogen levels:

"When males were treated with fadrozole (an aromatase inhibitor), aggressive behavior was reduced, although castration did not reduce aggression."​

SOURCE: Individual differences in estrogen receptor alpha in select brain nuclei are associated with individual differences in aggression. - PubMed - NCBI​

Here are symptoms of hyperandrogenism:

• Hirsutism - male-pattern hair growth.
• Alopecia - balding.
• Masculine appearance.
• Hidradenitis suppurativa.
• Polycystic ovarian syndrome.
• Oligomenorrhea - menstrual irregularities.
• Acne.
• Obesity.

Hirsutism - male-pattern hair growth. (and its correlation insulin resistance caused by estrogen, which contributes to obesity and metabolic syndrome)

"...women, who have androgen and estrogen excess, also have altered apolipoprotein metabolism, which correlates with insulin resistance. They often have android obesity, which appears to aggravate their metabolic alterations. Insulin resistance seems to have more of an influence on altered apolipoprotein metabolism than does endogenous ovarian androgen or estrogen, at least in hirsute women who are obese. It is hypothesized that adrenal dehydroepiandrosterone sulfate may modify the effects of insulin resistance, as reflected in androgen and apolipoprotein lipid metabolism. These hormonal interactive influences, which require further investigation, may hold clues to why men and women differ in the time of onset of the multifactorial problem of coronary vascular disease."​

Hidradenitis suppurativa occurs more often in women:

"HS is more common in women, and the disease severity appears to vary in intensity according to the menstrual cycle."​

"...decreasing levels of progesterone and estrogen seem to coincide with disease flares in premenopausal women..." [and assumedly a declining progesterone to estrogen ratio, given what we know about menopause]​

SOURCE: The Role of Androgens and Estrogens in Hidradenitis Suppurativa - A Systematic Review. - PubMed - NCBI​

Testosterone can certainly increase aggression through its conversion into estrogen, and it's well known that bodybuilders who use anabolic steroids suffer from acne, mood swings and aggression, weight gain without adding an aromatase inhibitor (AI), and it's reasonable to posit that other side effects of using AAS including the sometimes drastic hair loss may involve estrogen as well.

"Testosterone treatment significantly increased manic scores on the YMRS (P=.002), manic scores on daily diaries (P=.003), visual analog ratings of liking the drug effect (P=.008), and aggressive responses on the Point Subtraction Aggression Paradigm (P=.03)."​

SOURCE: Effects of Supraphysiologic Doses of Testosterone on Mood and Aggression in Normal Men​

As a side note, weight gain appears alongside hot flashes, and progesterone relieves both hot flashes and obesity:

"...weight gain was independently associated with hot flash occurrence (OR 2.1, 95% CI 1.1–4.4) and hot flash severity (OR 2.6, 95% CI 1.3–5.0) ...these results support the thermoregulatory model of hot flashes and argue against a protective effect of body fat in this population."​

SOURCE: Weight gain is associated with increased risk of hot flashes in breast cancer survivors on aromatase inhibitors​

"Oral micronized progesterone is effective for treatment of hot flushes and night sweats in healthy women early in postmenopause."​

SOURCE: Oral micronized progesterone for vasomotor symptoms--a placebo-controlled randomized trial in healthy postmenopausal women. - PubMed - NCBI​

Estrogen strongly correlates with endometrial cancer, obesity and insulin resistance:

"In the normal endometrium, the proliferative effects of estrogen are normally countered by progesterone,...One of the major emerging causes of the estrogen/progesterone imbalance is obesity. Obesity is associated with several hormonal derangements as well as dysregulation of insulin/insulin-like growth factor activity, which collectively contribute to hyperplasia and carcinogenesis in the endometrium. Given that endometrial cancer is clearly associated with obesity, we put forth the hypothesis that a large portion of these cancers might be prevented by treatment with progesterone."​

SOURCE: Catch It Before It Kills: Progesterone, Obesity, and the Prevention of Endometrial Cancer​

"...Waist circumference was the best predictor of progesterone levels in a multivariate model including steroid concentrations as well as waist circumference, BMI and subcutaneous adipocyte diameter. In conclusion, plasma progesterone was negatively associated with markers of obesity such as BMI, waist circumference and subcutaneous adipocyte diameter in this sample of men. Circulating DHEA-S level was the best steroid correlate of plasma progesterone. We suggest that the low progesterone levels observed in obese men may reflect decreased adrenal C(19) steroid production in the adrenal cortex. Further research is needed to confirm this hypothesis." [Given what we know about stress, it's likely that the progesterone elevations in the context of elevated pertain to its protective role against estrogen.]​

SOURCE: Circulating progesterone and obesity in men. - PubMed - NCBI​

Hypogonadism (and low testosterone) has a strong correlation with obesity (in accordance with the study above that I posted, which shows the appearance of insulin resistance in women with hirsutism):

"Low testosterone levels are frequently encountered in obese men who do not otherwise have a recognizable hypothalamic-pituitary-testicular (HPT) axis pathology. Moderate obesity predominantly decreases total testosterone due to insulin resistance-associated reductions in sex hormone binding globulin. More severe obesity is additionally associated with reductions in free testosterone levels due to suppression of the HPT axis. Low testosterone by itself leads to increasing adiposity, creating a self-perpetuating cycle of metabolic complications. Obesity-associated hypotestosteronemia is a functional, non-permanent state, which can be reversible, but this requires substantial weight loss. While testosterone treatment can lead to moderate reductions in fat mass, obesity by itself, in the absence of symptomatic androgen deficiency, is not an established indication for testosterone therapy. Testosterone therapy may lead to a worsening of untreated sleep apnea and compromise fertility. Whether testosterone therapy augments diet- and exercise-induced weight loss requires evaluation in adequately designed randomized controlled clinical trials."​

SOURCE: Lowered testosterone in male obesity: mechanisms, morbidity and management​

As a side note, estrogen's implicated in sleep apnea and increased FSH (which decreases fertility):

"...those with an apnea-hypopnea index (AHI) greater than 10/hrs of sleep had significantly lower levels of 17-OH progesterone, progesterone, and estradiol..." [and again an assumedly worse progesterone to estrogen ratio which regularly appears in menopause]​

SOURCE: Women with sleep apnea have lower levels of sex hormones. - PubMed - NCBI​

"Follicle-stimulating hormone (FSH) levels are not suppressed as rapidly or to the same degree as luteinizing hormone (LH) levels in ovariectomized rats treated with either gonadotropin-releasing hormone (GnRH) antagonist or estrogen. The acute inhibitory effects of various doses of estrogen on FSH and LH secretion were examined in cannulated, 2-wk ovariectomized rats. No dose of 17 beta-estradiol, up to 2,500 ng injected intravenously, suppressed FSH..."​

SOURCE: Estrogen inhibition of LH and FSH secretion: effects of a GnRH antagonist. - PubMed - NCBI​

Posted on my blog: Depression, Cortisol and Male Pattern Baldness

 

[xetawaves]

So do you guys believe that the follicles completely die or are just dormant and able to be fully revived?

 

[Luckytype]

Turned off.

Its much too expensive to risk having to grow it again compared to just cutting power to it.

Other cases of this are with muscle. An observed disinhibition(turning off the "off" switch of a functional unit) comes long before size growth in untrained individuals and in those trained but deconditioned

 

[Travis]

"Measurements of serum androgens, testosterone, dihydroepiandrosterone sulphate (DHEA), and free testosterone levels have failed to demonstrate a reproducible difference between cases and controls [for androgenic alopecia] (51). A study that assessed different hormonal levels in MAA and age-matched controls measured elevated levels of cortisol and androstenedione in those experiencing MAA [male androgenic alopecia] (52). This study further suggests a broad range of hormones may influence androgenetic alopecia. Even though scalp hair loss and hirsutism are essential features of hyperandrogenism in women, several investigations failed to demonstrate raised androgen levels in women (53). Therefore it is suggested that normal levels of androgens are sufficient to cause hair loss in genetically susceptible individuals."​

This quote is hilarious, and exemplifies the type stubborn illogical thinking characteristic of middle‐aged researchers and medical doctors desperately clinging to a false paradigm to just save their profits and ego. Despite the author admitting there there is no real 'reproducible difference' in androgens observed, and hair loss is actually seen with 'low testosterone levels,' the author concludes that androgens surely must be the cause and they can cause hair loss despite this. He says this despite the fact that Valerie Randall has shown hair follicles to have practically no androgen receptors and DHT actually stimulates hair growth by acting on the ones the do have (and the ancillary papilla cells), just as they do on hair follicles everywhere else.

selenium disulphide is a prostaglandin D2 antagonist.

Ramatroban and Setipiprant are prostaglandin D₂ antagonists, acting as a displacing ligand on the cell membrane's receptors with first‐order kinetics. Selenite appears to inhibit cytokine translation by becoming a catalytic amino acid of glutathione peroxidase (as selenocysteine) which modifies redox‐sensitive transcription factors in the cell nucleus. These redox‐sensitive transcription factors are thought to transcribe for cytokines, meaning the cell produces defensive cytokines in response to H₂O₂. This has been proven in mast cells and mast cells do constitute a fraction of the skin. The selenite ion reduces prostaglandin D₂ levels ostensibly by reducing the cytokines which help to raise them.

 

[xetawaves]

Something else I've noticed is that a lot of the people I know that play tons of video games or sit and watch tv all day have thinning hair. Most software developers also have thinning hair. I assume this is from sitting slouched over all day with poor posture.

 

[Luckytype]

Something else I've noticed is that a lot of the people I know that play tons of video games or sit and watch tv all day have thinning hair. Most software developers also have thinning hair. I assume this is from sitting slouched over all day with poor posture.

With the exception of professional gamers(who likely can cope with the emotional stessors) also consider why people game and what kinds of coping mechanisms(cool heads vs raging) some of these guys have. I definitey see this too but im leaning toward stresses of situation too

 

[nbznj]

in the context of a very high cortisol does it make sense to use exogenous testosterone which is basically stable 24/7 and totally prevents cortisol from going anywhere?

I don't remember having read cases of hypo cortisolism when doing a TRT. SERMs and HCG were always a "meh" for me, and for many people it seems. I've done TRT / other androgens in the past and god, what a life it is with cortisol nice and low.

 

[DaveFoster]

So do you guys believe that the follicles completely die or are just dormant and able to be fully revived?

This quote is hilarious, and exemplifies the type stubborn illogical thinking characteristic of middle‐aged researchers and medical doctors desperately clinging to a false paradigm to just save their profits and ego. Despite the author admitting there there is no real 'reproducible difference' in androgens observed, and hair loss is actually seen with 'low testosterone levels,' the author concludes that androgens surely must be the cause and they can cause hair loss despite this. He says this despite the fact that Valerie Randall has shown hair follicles to have practically no androgen receptors and DHT actually stimulates hair growth by acting on the ones the do have (and the ancillary papilla cells), just as they do on hair follicles everywhere else.

Indeed. You just need to avoid all commentary most of the time and just reference data: something Dr. Peat does in his interviews, as with, "There was a study that showed x."

So do you guys believe that the follicles completely die or are just dormant and able to be fully revived?

Anecdotally, I know people who have regrown their hair (from MPB) after taking thyroid.

Again, anecdotally, my hair will start to fill in if I keep my stress low (as after I've been taking lamotrigine, which lowers cortisol.) I've begun to see some longer vellus hairs start to fill in my crown.

Burn victims can regrow their hair.

Propecia (finasteride) can regrow hair (and not merely prevent its loss,) but it's a dangerous drug.

People who use red light lazer helmets like Over Macho Grande: Laser Therapy LLLT for Hair Loss | OverMachoGrande.com

Calcification's reversible.

Something else I've noticed is that a lot of the people I know that play tons of video games or sit and watch tv all day have thinning hair. Most software developers also have thinning hair. I assume this is from sitting slouched over all day with poor posture.

It's more likely from a lack of sunlight and downregulation of cytochrome c oxidase.

"low-intensity red and near-infrared light is acting on cells through a primary photoacceptor: cytochrome C oxidase, the terminal enzyme of the mitochondrial electron transport chain."

SOURCE: Low-Intensity Light Therapy: Exploring the Role of Redox Mechanisms

"thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate mitochondrial function in human epidermis...all HPT-axis members increased gene and protein expression of mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1)...T3 and TSH increased follicular heat production, whereas T3/T4 and TRH stimulated ATP production in cultured HF keratinocytes [epidermal cell]...T3 and T4 reduced ROS formation"

In regard to light therapy for MPB:

"LLLT is proposed to act by stimulation of mitochondria to produce more ATP and cyclic AMP, with activation of response to oxidative stress,[30–32] displacing NO from the cells and allowing more oxygen to enter."

SOURCE: Controversy: Is There a Role for Adjuvants in the Management of Male Pattern Hair Loss?

"Reactive oxygen species (ROS) cause sebaceous gland hyperplasia, promoting increased type I 5-AR enzyme activity and higher DHT formation.[15] Action of androgens is mediated through increased generation of superoxide, which is neutralized by super oxide dismutase (SOD).[15]"

Another study suggests an alternate mechanism of action of DHT resulting in miniaturization of hair follicles. According to this hypothesis, the adult cranial bones, especially the frontal and parietal bones, continue to grow in size even in adulthood under the influence of DHT, thus resulting in bone expansion and remodeling, which, in turn, compromises the blood flow through the capillary network in these areas and thus initiates miniaturization of hair follicles in the affected area.[18]"

SOURCE: Controversy: Is There a Role for Adjuvants in the Management of Male Pattern Hair Loss?

IGF-1 has anabolic effects on bone, but not the flat bones of the skull:

"With the exception of the flat bones of the skull and the clavicle, bone formation in the embryo occurs through an endochondral process that begins when mesenchymal stem cells form clusters or condensations via adhesion molecules."

SOURCE: Role of IGF-I Signaling in Muscle Bone Interactions

I might continue this later.

 

[nbznj]

nvm

 

[ddjd]

https://www.researchgate.net/profil...uinea_pigs/links/0046353c6c531d6599000000.pdf

These results show for the first time that only small amounts of systemically administered radioactive glucocorticoids are deposited in hair of guinea pigs, while measurement of large amounts of unlabeled GCM strongly suggests local production of glucocorticoids in hair follicles​

So that's basically the interesting part. Cortisol is massively produced in the hair follicles. I was listening to a KMUD interview with Ray, and he was saying that a lot of estrogen is produced in the skin, more than in the ovaries (of course also in men, LOL). I think ditto in the follicles and this probably has a lot to do with hair loss.

I think we're gonna find that in stress, the hair follicles create a lot of cortisol and estrogen and all the other stress hormones and that this causes hair loss. Pretty much like Danny Roddy has said.

What is interesting to me is that this occurs on the hair on the head but not on the chin or pubic region.

I think that most likely, there is a reason for this. Perhaps over the millennia, we have done better as men when we were bald if we were under stress, in order to get more sunlight on her scalp. I'm totally not kidding.

How do you explain the fact that taurine (an Adrenaline antagonist) stops hair loss and can even reverse it. I think maybe Adrenaline is more destructive than cortisol

 

[Wagner83]

How do you explain the fact that taurine (an Adrenaline antagonist) stops hair loss and can even reverse it. I think maybe Adrenaline is more destructive than cortisol

If it contracts blood vessels to keep the core warm and people end up with cold extremities then the scalp may be affected too.