Theory As To Why Hair Follicles In The Androgenetic Alopecia Region Have Higher 5ar Expression Than Occipatal Zone

[Feelsbadman.jpg]

I have been doing some research on the metabolic effects of dutasteride in light of studies showing increased risk for type 2 diabetes and NAFLD and in the process, may have stumbled upon a (partial) explanation as to why 5AR is expressed in higher amounts in certain areas of the scalp apart from simply saying, "it's genetic". Everything is a genetic reaction to environment and this is an attempt to explain the mechanisms behind this "genetic" expression. This is largely speculation but I do believe there is merit to it.

Firstly, do 5AR levels differ in amount from different regions of the scalp? This study says yes.

https://www.hindawi.com/journals/bmri/2014/767628/

However, most women with FPHL have no other signs or symptoms of hyperandrogenism and have normal androgen levels, indicating that our understanding of the pathogenesis of the disorder remains incomplete. The age-related increase in FPHL and the highest rates in postmenopausal women may suggest a protective role of the estrogen. Supporting this theory, Sawaya and Price conducted a study in 12 young women and 12 young men (ages from 14 to 33) suffering from Androgenetic Alopecia or FPHL [15]. Scalp biopsies were taken and androgens, expression of androgen receptor, type I and type II 5-reductase, and cytochrome p-450 aromatase enzyme genes were measured in hair follicles. Both young women and young men had higher levels of type I and type II 5-reductase and androgen receptors in frontal hair follicles compared to occipital hair follicles explaining probably the patterned hair loss. However, the levels in women were approximately half the levels in men [15]. The findings of this study suggest that the milder expression of FPHL may in part be the result of lower levels of 5-reductase and androgen receptors in frontal follicles of women compared to levels in men. Additionally, young women had much higher levels of cytochrome p-450 aromatase, enzyme capable of converting testosterone to estradiol, in frontal and occipital follicles than men. Those notable increased aromatase levels seem to play a protective role in the development of hair loss in women [15]. Furthermore, supporting the androgen-dependent etiopathogenesis, low levels of sex hormone-binding protein (SHBG), glycoprotein that binds to androgens, inhibiting thereby their activities, have been linked to diffuse hair loss [16]. Another part of FPHL and Androgenetic Alopecia pathogenesis is the gradual shortening of the growth phase of hair follicles. Over the successive hair cycles, the duration of anagen phase shortens from a normal duration of a few years to only weeks to months [2].

So what causes elevated 5AR levels? Based on the following studies focusing on metabolic effects of 5 AR inhibitors, 5AR levels increase to enhance glucocorticoid (cortisol) clearance. Glucocorticoids in the presence of insulin can promote fat gain and NAFLD (non-alcholic fatty liver disease) which in turn worsens insulin sensitivity. As a protective mechanism, 5AR increases to lower glucocorticoids and preserve hepatic phenotype.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701851/

Clinical studies have highlighted the potential role for 5α-reductase in the regulation of metabolic phenotype, although there is still debate as to whether the abnormalities observed represent the cause or consequence of disease. Cross-sectional studies have demonstrated increasing 5α-reductase activity with insulin resistance (12) and increasing adiposity (10) and decreases after weight loss (29). A recent study examined the metabolic impact of selective SRD5A inhibition in humans (16). After a 3-month treatment period, they observed inhibition of insulin-mediated suppression of global lipolysis by dutasteride as well as a reduction in peripheral insulin sensitivity, which they suggested might reflect the role of SRD5A1 within skeletal muscle. In comparison with the current study, there are important differences to consider in terms of the duration of treatment, volunteer demographics (age, BMI), and methodology (adipose microdialysis, doses of insulin used in the clamp studies, MRS to quantify liver fat before and after treatment) as well as the analysis of the serum metabolome. Taken together, these studies would seem to complement each other and provide evidence as to the potential detrimental impact of the dual SRD5A1 and SRD5A2 inhibition.

https://www.endocrine-abstracts.org/ea/0019/ea0019oc18

Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD, is highlighted by patients with GC excess, Cushing’s syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1) or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR).

We characterised metabolic phenotype and hepatic cortisol metabolism in patients with histologically proven NAFLD (n=15) compared with a BMI-matched control group (n=30).

Intra-hepatic fat (measured by liver:spleen attenuation ratio (L:S) on CT) was significantly higher in the NAFLD group (L:S 0.81±0.08 vs 1.13±0.04, P<0.01). Twenty-four hours urinary steroid metabolite analysis by GC/MS showed increased 5αR activity in patients with NAFLD (5αTHF/THF ratio, 1.12±0.22 vs 0.80±0.07, P<0.01). Absolute values of all 5α-, and not 5β-reduced metabolites, were significantly increased in the NAFLD group. Furthermore, total cortisol metabolites were increased in the NAFLD group indicative of increased GC production rate (12168±1028 vs 8690±786 μg/24 h, P<0.01). Fasting serum free fatty acids were increased in the NAFLD group (422±54.9 vs 335±16.9 μmol/l, P<0.05) and correlated with the 5αTHF/THF ratio in both groups (r=0.4, P<0.05).

Endorsing these clinical observations, immunohistochemical analysis of NAFLD liver biopsies confirmed increased 5αR1 and 2 expression. 11β-HSD1 activity measured by both urinary steroid metabolite ratios and cortisol generation profiles after oral cortisone acetate 25 mg, did not differ between NAFLD and controls.

In conclusion, patients with NAFLD have increased hepatic metabolism of cortisol due to increased 5αR activity with concomitant HPA axis activation. We propose that this represents a compensatory mechanism to decrease local GC availability in an attempt to preserve hepatic metabolic phenotype.
Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD, is highlighted by patients with GC excess, Cushing’s syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1) or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR).

We characterised metabolic phenotype and hepatic cortisol metabolism in patients with histologically proven NAFLD (n=15) compared with a BMI-matched control group (n=30).

Intra-hepatic fat (measured by liver:spleen attenuation ratio (L:S) on CT) was significantly higher in the NAFLD group (L:S 0.81±0.08 vs 1.13±0.04, P<0.01). Twenty-four hours urinary steroid metabolite analysis by GC/MS showed increased 5αR activity in patients with NAFLD (5αTHF/THF ratio, 1.12±0.22 vs 0.80±0.07, P<0.01). Absolute values of all 5α-, and not 5β-reduced metabolites, were significantly increased in the NAFLD group. Furthermore, total cortisol metabolites were increased in the NAFLD group indicative of increased GC production rate (12168±1028 vs 8690±786 μg/24 h, P<0.01). Fasting serum free fatty acids were increased in the NAFLD group (422±54.9 vs 335±16.9 μmol/l, P<0.05) and correlated with the 5αTHF/THF ratio in both groups (r=0.4, P<0.05).

Endorsing these clinical observations, immunohistochemical analysis of NAFLD liver biopsies confirmed increased 5αR1 and 2 expression. 11β-HSD1 activity measured by both urinary steroid metabolite ratios and cortisol generation profiles after oral cortisone acetate 25 mg, did not differ between NAFLD and controls.

In conclusion, patients with NAFLD have increased hepatic metabolism of cortisol due to increased 5αR activity with concomitant HPA axis activation. We propose that this represents a compensatory mechanism to decrease local GC availability in an attempt to preserve hepatic metabolic phenotype.

So in the presence of increased glucocorticoid production, the response of the organ is to increase 5AR to increase glucocorticoid metabolism into inactive metabolites in order to preserve metabolic phenotype (by enhancing glucocorticoid clearance, the opportunity for cortisol to interact with insulin to promote hepatic lipid accumulation is minimized). 5AR is a protective mechanism for excessive cortisol and the increased level of DHT could quite possible just be an unintended consequence.

If we extrapolate this model into the hair follicle (this is a bit of a leap but it seems probable to me, the hair follicle is an organ after all), the zones that have higher 5AR have higher glucocorticoid production. Can hair follicles actually synthesize glucocorticoids peripherally (inside the hair follicle itself) though?

According this study, yes.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3381079/

Cortisol has major impacts upon a range of physiological homeostatic mechanisms and plays an important role in stress, anxiety and depression. Although traditionally described as being solely synthesised via the hypothalamic-pituitary-adrenal (HPA) axis, recent animal and human studies indicate that cortisol may also be synthesised via a functionally-equivalent ‘peripheral’ HPA-like process within the skin, principally within hair follicles, melanocytes, epidermal melanocytes and dermal fibroblasts. Current data indicate that basal levels of cortisol within hair vary across body regions, show diurnal variation effects, respond to the onset and cessation of environmental stressors, and may demonstrate some degree of localisation in those responses. There are conflicting data regarding the presence of variability in cortisol concentrations across the length of the hair shaft, thus challenging the suggestion that hair cortisol may be used as a historical biomarker of stress and questioning the primary origin of cortisol in hair. The need to comprehensively ‘map’ the hair cortisol response for age, gender, diurnal rhythm and responsivity to stressor type is discussed, plus the major issue of if, and how, the peripheral and central HPA systems communicate.

Not only is cortisol made in the hair follicle, but their is the functional equivalent of the HPA axis in hair follicles. This means there is a negative feedback loop as well. When Cortisol is high, signals are sent to stop making more and vice versa. With overactive 5AR, this can create a vicious feed forward cycle. Due to high glucocorticoid release, 5AR is increased and clears out the glucocorticoid which in turn signals for the release of more glucocorticoid and in turn more 5AR is produced. High 5AR can overstimulate the HPA axis potentially.

From the same study

Prolonged and elevated expression of cortisol leads to increased serum lipids, endothelial damage and resultant incidence of coronary heart disease (CHD)

This could be the link (or part of it) between male pattern baldness and cardiovascular disease. High glucocorticoids and consequently, high 5 AR to clear them out.

So what causes hair follicles to increase glucocorticoid production? Well we know that Botox actually regrows hair.

 

[Feelsbadman.jpg]

From the Discussion section of this study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5782443/

The exact pathogenesis of male pattern baldness is not yet known. There are various causative factors implicated in causation of male pattern baldness. Orentreich[6] proposed that minituarization of hair follicles occurs in genetically predisposed androgen-sensitive hair follicle. This androgenetic theory has been the most prevailing theory for male pattern baldness and antiandrogens such as finasteride are successfully used for the management of this condition.[6] Zappacosta[7] described treatment of male pattern baldness in patients receiving minoxidil for hypertension, and suggested topical minoxidil as an effective treatment. Few experimental studies suggested that subcutaneous blood flow in the scalp of a patient with male pattern baldness was greatly reduced as compared to controls. Goldman et al.[8] conducted an experiment in which they measured transcutaneous pO2 of the scalp in male pattern baldness and to find out whether bald scalp actually has some microvascular insufficiency. They found that resting transcutaneous pO2 was significantly lower in frontal bald scalp as compared to temporal hair-bearing scalp in patient with male pattern baldness. Transcutaneous pO2 in frontal bald scalp was also significantly lower as compared to hair-bearing frontal scalp of controls and transcutaneous pO2 of hair-bearing frontal and temporal scalp in controls were not significantly different.[8] This relative microvascular insufficiency possibly results because frontal and vertex areas are supplied by supratrochlear and supraorbital arteries, which are smaller branches of internal carotid artery, and it overlies galea aponeurotica, which is relatively less vascular as compared to the temporal and occipital areas, which overlie muscles.[9] The androgenetic theory states that minituarization of hair follicle results from the action of DHT. Hair follicles contain 5α-reductase enzyme that is responsible for peripheral conversion of testosterone to more active DHT. There is an increased accumulation of DHT in the affected follicle and disturbed DHT to estradiol ratio due to relative microvascular insufficiency, which leads to minituarization of hair follicle.[10]

Injection of botulinum toxin relaxes the muscle, which reduces pressure on the musculocutaneous and perforating vasculature, thereby potentially increasing the blood supply and transcutaneous pO2. This increased blood flow can also lead to washing out of accumulated DHT, thereby reducing the signal for minituarization of hair follicle. We found that botulinum toxin is an effective therapy for Androgenetic Alopecia management in our pilot study; however, larger studies and controlled trial to compare it with existing FDA-approved modalities need to be conducted. Transcutaneous pO2 and blood supply before and after botulinum injection, if conducted, will also provide some insight into the pathogenesis of this common disease and mechanism of action of botulinum toxin in Androgenetic Alopecia management.

The authors believe that botulinum toxin works for Androgenetic Alopecia due to increased blood flow which "washes out" accumulated DHT. I don't believe this to be the correct explanation. By relieving tension and improving blood flow, hair follicles are less compromised metabolically which in turn will reduce glucocorticoid production which in turn also reduces the need for 5AR and results in decreased 5AR levels in the follicle.

To be clear, I am not stating that scalp tension and lack of blood flow are the cause of Androgenetic Alopecia (not directly anway). While these issues will negatively effect the hair follicle and lead to poor hair growth, I don't believe they will result in Androgenetic Alopecia by themselves. It is the stress that these factors place on the hair follicle that leads to higher 5AR levels in order to metabolize the higher levels of glucocorticoids that are produced in this stressed (literally) environment that leads to higher DHT which causes Androgenetic Alopecia. I believe DHT is an unintended byproduct from the organ's attempt to mitigate the detrimental effect excessive glucocorticoid exposure on metabolic phenotype through increased 5 alpha reductase. I am basing this off of the results of studies done on 5 alpha reductase and liver metabolism as it pertains to nonalcoholic fatty liver disease.

Nature is not perfect. No organism can be perfectly adapted to a dynamic and ever changing environment and I believe our body's solution to excessive glucocorticoid production is evidence to this. In this study https://www.ncbi.nlm.nih.gov/pubmed/24080367, 60% of rats fed a western diet w/ sedentary lifestyle developed liver cancer after 1 year. Rats fed the same diet but had 5AR1 inhibited developed NAFLD faster, but 0% had liver cancer after 1 year. This is most likely due to the carcinogenic nature of DHT. So increasing 5AR in the short term provided benefit by lessening NAFLD but in the long run led to cancer because of the unintended(by this I mean the organ's purpose of increasing 5AR was to clear glucocorticoids, not produce DHT) byproduct from 5AR, DHT.

Studies showing androgen receptor signalling involved in liver cancer.
https://www.ncbi.nlm.nih.gov/pubmed/17369855
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110552/

To superimpose this scenario on to a separate organ, the hair follicle, does not require a leap of faith. Hair follicles under duress over produce glucocorticoids and in an attempt to metabolize and deactivate the excess cortisol inadvertently subject themselves to the processes of Androgenetic Alopecia due to the overproduction of DHT, the carcinogenic byproduct of metabolizing cortisol through 5AR

To reiterate, this is not an attempt to discredit the role of androgens in Androgenetic Alopecia, it is merely offering an explanation as to why the 5AR enzyme is expressed so highly in certain areas of the scalp and not others.


So why do follicles in the occipatal zone have less 5AR? I think it is because they are not under any tension or physical duress that interferes with normal metabolic activity to any appreciable degree and therefore don't produce excessive glucocorticoids.

This thread interestingly maps out structural stress of the scalp through an engineering technique called Von Mises Model and I feel it does accurately lay out stress points and tension which fall in line with the typical Androgenetic Alopecia pattern.

https://www.hairlosstalk.com/intera...alopecia-von-mises-2d-analysis-models.113276/

So anything that "stresses" (by stress I mean interfere with normal metabolic function) the follicle could result in increased glucocorticoid production and consequently increased 5AR.

Other theories about scalp tension include skull expansion. DHT plays a role in bone growth and calcium metabolism. Danny Roddy has talked extensively about parathyroid hormone and it's relation to hair loss. Perhaps bone growth in combination with depleting subcutaneous fat layers exerts pressure on the follicles resulting increased glucocorticoid production.

Another avenue could be fluid pressure. Minoxidil works by opening up potassium channels supposedly. Interestingly, DHT increases aldosterone, a hormone which elevates sodium potassium ration in favor of sodium and increases blood pressure. https://www.ncbi.nlm.nih.gov/pubmed/19428991

Point is botox did not work for everyone in the study. Scalp tension may be caused by multiple factors and not just one.



There is also the 800 lb gorilla still dominantly asserting its position against this theory: Hair Transplants.

Why do they not suffer the same fate if they are transplanted into a tense cortisol inducing environment? I don't have a satisfactory answer for this but I don't believe this is a contradiction and that there is a logical explanation, I just can't see it yet.

Some initial thoughts are:

Hair transplants are implanted deeper into the dermis than endogenous follicles and capillary networks are built up around the implants.

Perhaps follicles taken from the occipatal zone do not have the capacity to produce as much glucocorticoids as follicles native to the Androgenetic Alopecia zone. Perhaps the stress response is set in when the follicles are being created?

 

[Schmiggy]

Is there study that looks at the true longevity of hair transplants? Strictly anecdotally speaking I see a lot of good results a year or 2 out, but in person I’ve seen a ton of strip scars with nothing left on top. Are we 100% certain those transplanted follicles are immune to the affects of the zone they are transplanted into?

 

[Koupka]

Is there study that looks at the true longevity of hair transplants? Strictly anecdotally speaking I see a lot of good results a year or 2 out, but in person I’ve seen a ton of strip scars with nothing left on top. Are we 100% certain those transplanted follicles are immune to the affects of the zone they are transplanted into?

that's a good question.
I've also seen quite a few bald men with a huge FUT strip but nothing less than maybe 10-20 hairs on top of their scalp, especially at the hairline.

 

[Koupka]

All in all everything is already known, it's all about tension, bloodflow etc.
This just explain well or better the process the scalp goes when you start loosing your hair.

 

[Feelsbadman.jpg]

Is there study that looks at the true longevity of hair transplants? Strictly anecdotally speaking I see a lot of good results a year or 2 out, but in person I’ve seen a ton of strip scars with nothing left on top. Are we 100% certain those transplanted follicles are immune to the affects of the zone they are transplanted into?

https://www.ncbi.nlm.nih.gov/pubmed/12269871

Recently hair transplantation has been widely applied not only to correct androgenetic alopecia, but also to correct hair loss on other parts of the body such as the eyebrows and pubic area. It is believed that the transplanted hairs will maintain their integrity and characteristics after transplantation to new nonscalp sites.

OBJECTIVE:
To evaluate whether the transplanted hairs maintain their hair growth characteristics after transplantation to a new anatomic site other than the scalp.

METHODS:
Three study designs were used. Study I: Hair transplantation from the author's occipital scalp to his lower leg was performed and clinical evaluations were made at both 6 months and at 3 years after the transplantation. Study II: After finding changes in hair growth characteristics, transplanted hairs were harvested from the leg and retransplanted to the left side of the nape of the neck (group A). As a control study, occipital hairs were transplanted to the opposite side (group B). Observations were made at 6 months after the operation. Study III: An observational study was done in 12 patients with androgenetic alopecia about 1 year after transplantation of occipital hair to frontal scalp. At each step, survival rates were documented and the rate of growth and the diameter of the shafts were measured for both recipient and donor sites.

RESULTS:
Study I: Surviving hairs on the lower leg showed a lower growth rate (8.2 +/- 0.9 mm/month), but the same diameter (0.086 +/- 0.018 mm) compared with occipital hairs (16.0 +/- 1.1 mm/month, 0.088 +/- 0.016 mm). The survival rate 3 years after transplantation was 60.2%. Study II: There was no significant difference in the growth rate, shaft diameter, and survival rate between retransplanted hairs (group A) and controls (group B). Groups A and B showed a lower growth rate, but the same diameter, compared with occipital hairs. Study III: There was no significant difference in the growth rate and shaft diameter between the transplanted hairs on the frontal scalp and the occipital hairs.

CONCLUSION:
These results strongly suggest that the recipient site affects some characteristics of transplanted hairs, such as their growth and survival rates.

This is only 1 year but it shows no change, they grow just fine in frontal scalp with no change in diameter.

I have heard of anecdotal reports of transplant hairs beginning to thin after x amount years (there are even more reports of the hair growing just fine though), some even on this board but I do not know of any studies that evaluate hair transplants after 10 years.

One thought I had is, if you are transplanting into a bald/mostly bald area, the structural changes have already happened and the transplanted hairs have a capillary network built in this environment so there is not much change from that point onward.

 

[Feelsbadman.jpg]

All in all everything is already known, it's all about tension, bloodflow etc.
This just explain well or better the process the scalp goes when you start loosing your hair.

Yea no. Everything is not already known. Not even close. Tension and blood flow alone do not explain Androgenetic Alopecia. Where are you getting your information?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536995/pdf/jnma00008-0023.pdf

“If we accept that the main androgen hormone active on the skin target cells is dihydrotestosterone, a metabolite of circulating testosterone, then the enzymatic control of the alpha-reduction
of testosterone into dihydrotestosterone is assumed by the 5-alpha-reductase. If this enzyme can be inhibited in the scalp, seborrheic alopecia will probably be reduced. One of the most powerful non-toxic enzyme inhibitors is hypoxia. Through surgery, by ligature of the scalp arteries, hypoxia can be induced in the scalp (by reducing the speed of the normal blood flow through replacing the arterial flow by capillaries and by obtaining a diminished P02 in the ligated area). By creating hypoxia in the scalp, testosterone metabolism will be reduced and the condition improved.”

Results
Of the 1300 cases followed, 987 patients had very favorable results. Approximately 76 percent of cases revealed a reduction in hair shedding. A lengthening of the time necessary for the hair to become greasy (rarefying dandruff and reducing scalp itching) was also noted. Results are obtained at variable periods of time. Often, improvement of seborrhea comes before improvement of hair loss. Sometimes, it appears as soon as the 15th day; but usually, four to eight months are required before improvement reaches its maximum level or complete cure is obtained. None of those who had surgery showed recurrence of the illness. Approximately 17 percent of cases showed a regrowth of hair at the bald regions. Twenty-four percent of patients having ligature of the arteries of the scalp showed no improvement in their seborrheic alopecia.

Complete opposite of what you are proposing.

 

[Koupka]

Yea no. Everything is not already known. Not even close. Tension and blood flow alone do not explain Androgenetic Alopecia. Where are you getting your information?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536995/pdf/jnma00008-0023.pdf



Complete opposite of what you are proposing.

well, quoting from the study you've linked :
how does the blood arrive in the ligated area?
The blood of the neighboring regions
penetrates the adjacent capiliaries in
order to establish a non-pulsed circula-
tion in the ligated area.

Ligaturing arteries does pretty much the same as minoxidil in fact, opening and allowing blood to go in the capiliaries. Tension doesn't shut off completely the blood flow in the main veins, there is still blood flow, but it's reduced to the main vascular system, not the peripherical.

I'm not saying there isn't blood anymore in the scalp, if it was the case skin would just necrose at some point. Also it would would required a lot of tension to shut off completely blood, and we would easely see it.
But all the skin isn't irrigate properly, especialy the peripherical capillaries, that are constricted.

 

[Koupka]

https://www.ncbi.nlm.nih.gov/pubmed/12269871


This is only 1 year but it shows no change, they grow just fine in frontal scalp with no change in diameter.

I have heard of anecdotal reports of transplant hairs beginning to thin after x amount years (there are even more reports of the hair growing just fine though), some even on this board but I do not know of any studies that evaluate hair transplants after 10 years.

One thought I had is, if you are transplanting into a bald/mostly bald area, the structural changes have already happened and the transplanted hairs have a capillary network built in this environment so there is not much change from that point onward.

unfortunatelu, one year isn't relevant for a long term study on hair.
And based on my anecdotal experience, i would be very surprise if transplanted graft would last more than 10-15 years without treatment anykind of treatment in the aponevrosis...
But prove me wrong !

 

[cyclonus]

Many guys have thinning in the donor area over the years, so its not that suprising that some transplants fail.

 

[OtyMac]

So what causes hair follicles to increase glucocorticoid production? Well we know that Botox actually regrows hair.

I'm not aware the hair follicles have increased glucocorticoid production but the serum levels of cortisol are definitely higher in male and female pattern loss. https://pubmed.ncbi.nlm.nih.gov/8003325/
Full study:

https://www.tesble.com/10.1159/000211275

What causes the increased serum cortisol? Vitamin D deficiency is one possibility according to this study:

Effect of vitamin D supplementation on cardiovascular disease risk factors and exercise performance in healthy participants: a randomized placebo-controlled preliminary study - PMC

Evidence suggests associations between vitamin D deficiency and cardiovascular disease (CVD) risk factors, including hypertension and excessive cortisol levels. Also, vitamin D levels may impact exercise performance. Thus, we aimed to investigate ...

pmc.ncbi.nlm.nih.gov

In the intervention arm, at day 14, vitamin D supplementation significantly reduced SBP and DBP from 115.8 ± 17.1 and 75.4 ± 10.3 at baseline to 106.3 ± 10.9 (p = 0.022) and 68.5 ± 10.1 mmHg (p = 0.012) respectively. Also arterial stiffness was markedly reduced in the vitamin D group (from 7.45 ± 1.55 to 6.11 ± 1.89, p = 0.049).

Urinary free cortisol levels and cortisol/cortisone ratio were significantly reduced from 162.65 ± 58.9 nmol/day and 2.22 ± 0.7 to 96.4 ± 37.2 (p = 0.029) and 1.04 ± 0.4 (p = 0.017) respectively

_______________________________________
Also if we look at the full study in males, the androstenedione, luteinizing hormone and E2 levels are also elevated:

• Vitamin D deficiency is associated with higher levels of estradiol (E2) in men:
  • Study 1
    Men with deficient or suboptimal 25(OH)D levels had higher serum levels of E2, free testosterone, and luteinizing hormone (LH).
  • 
    
  • Study 2
    Men with vitamin D deficiency (25(OH)D <50 nmol/l) had higher levels of E2 and LH.
    
    
  • 
    
  • Study 4
    Men with vitamin D deficiency had higher total and free E2 concentrations than men with higher vitamin D status.
  Vitamin D plays a role in regulating enzymes involved in the production of sex hormones. Vitamin D deficiency is also associated with lower testosterone/estradiol ratios in young men.
  
  
  
  
  AI Overview
  Learn more
  
  Vitamin D deficiency is associated with increased serum androstenedione levels in males. This is one of a number of ways that vitamin D deficiency can impact male hormone levels, including:
  • Testosterone
    Vitamin D deficiency is associated with decreased total and free testosterone levels.
  • 
    
  • SHBG
    A 10 ng/ml decrease in 25(OH)D is associated with an average difference of −0.70 nmol/L in SHBG.
  Vitamin D regulates the production of steroid hormones, including sex hormones. It also metabolizes enzymes in the testis and ejaculatory tract, and is associated with sperm maturity.
  
  
  
  To reach a serum level of 25(OH)D above 30 ng/ml, adults need at least 1000 IU of vitamin D per day, but likely 1500–2000 IU. The main causes of vitamin D deficiency are inadequate sun exposure and insufficient vitamin D consumption.
• 
  
• Link to the study of vitamin D and the 1000 IU appears to be on the low end for optimal health:
• https://www.hairlosstalk.com/intera...-d-deficiency-hair-loss-a-case-report.139172/