Back to the roots: Causes and effects of elevated DHT

[Ventures]

You are still confused about how male pattern baldness works.

The balding gene does not get 'activated'. The hair follicle miniaturizes under the cumulative effect of androgen exposure, something only DHT can do with high enough firepower to drive a hair follicle dead over a number of years. This is the simplest way I can explain it.

I didn't want to use word activate to confuse you or other users, more appropriate word used in that context would be regulate. I marked a sentence in your quote which is important to understand; By that you mean there is a threshold. And when that threshold of androgen stimulus on AR is reached, chemical/molecular signals are sent by certain paths and mechanisms. If intensity of that stimulus is less than threshold then nothing would happen, and no signal and instructions would be sent to nucleus. So, only if stimulus is equal or bigger than threshold, chemical signals which regulates balding process/instructions of DP would be sent to nucleus. According to you statement hair follicle can be exposed to certain androgen stimulus for infinitely long time, but as long as that stimulus is less than critical threshold, nothing would happen ?



Can you please give answers on this questions:

Do you think when DHT binds to AR site that "stimulus" is more stronger compared to stimulus when T binds to the same receptor ?
Do you think that DHT (dihydro-testosterone) and T transmit different signals/instructions after binding to the same AR or their only difference is how successfully /effectively they bind to AR site ?

Brian never said testosterone causes male pattern baldness. I believe he was always in support of the pseudohermaphrodite model.

Well, in this thread he gave explanation why is castration more effective in halting male pattern baldness: http://www.hairlosstalk.com/interac...8-DHT-levels?p=1089252&viewfull=1#post1089252

We used to get the occasional post from people who wonder and speculate about why castrated men have what appears to be a TOTAL suppression of male pattern baldness that apparently lasts for life, but for years I've always said that that's probably due to a more complete suppression of androgens than just what you get with finasteride. Castration causes about the same DHT suppression as finasteride, but causes a very striking reduction of testosterone, compared to what you get with finasteride (which actually tends to go UP a little).

The amount that gets converted to DHT by 5-AR depends on the amount of aromatase enzyme, SGBH, free testosterone quantities, and regulation of the androgen/estrogen ratio by the HPTA. It's generally around 5-10% in a normal healthy male. But it can be higher (or lower) otherwise, which is one of the reasons for the early prevalence of male pattern baldness in recent decades.

I definitely agree with your statement conversion process depends on the amount of aromatase enzyme, SGBH, (FreeT, T, DHT) / E ratio and other factors. It's pretty much stochastic process and we must consider all hormones and enzymes which compete with each other in order to bind to AR.

5-AR levels and activity does not really change in general. The changes are mostly signals from specific organs needing 5-AR metabolite molecules to function properly.

I believe 5-ard activity increases as we age, in order to produce stronger androgen effect in target tissues. Benjt has proposed theory of DHT as hormone for local amplification of androgen effects, other endocrine experts share this theory. It would be logical to assume body produces 5ard to generate more potent derivative of testosterone - DHT to compensate lack of total T. And this makes sense.

What exactly you mean by signals from specific organs. Do you think that body produces same quantity of 5ard in scalp, for instance, but AR in DP cells, sebaceous glands become more sensitive in old age ? And because of that they produce more sebum and you can see many old slick bald guys have very oily scalp.

The only scientific study showing AR upregulation was in the case of exogenous sexual steroid administration. Because testosterone increases the number of ARs and their sensitivity, like it increases protein synthesis around the whole body. So even though there is a 10% increase in T from finasteride, it is unlikely to cause a huge anabolic effect either way.

Hope this helps.

Can you please provide the link to that study ?

 

[xRedStaRx]

Hi,
where is the study about pseduohermaphrodites that never go bald?. Only there is a reference from Hamilton. I did read the work and it is not very good, ancient, scarcy methods of measuring hormones, a few people, and possibly other explanation. I could say the same with women..... BTW there is eunuchs suffering baldness, in Japan.
Regarding "Bald scalps have higher DHT/T ratio than non-balding scalps on the same person" I would like very much read a study in healthy persons,..., with different DHT in different zones of scalp. It is posible that the problem arise when you suffer from common baldness, and it is a consequence, not a cause ...
The androgenetic theory have many holes.....

Eunuchs do not go bald, if castration occurs before losing hair. This is commons knowledge.

 

[Ventures]

Eunuchs do not go bald, if castration occurs before losing hair. This is commons knowledge.

I think there is a plenty of evidence that castration (chemical, or surgical), despite when it it has been done, halts or to be more precise slows down process of Androgenetic Alopecia to a level which can be considered to be negligible or stopped. There are transsexual persons on oral spironolactone who do not loose hair, and even get decent regrowth.

The famous picture of "bald" chinese eunuch doesn't disprove this theory since the frontal loss of his hair might be because of several other reasons, after all exception doesn't always prove the rule, since there are lot more eunuchs who never went bald.

So, I think it is not correct to give statment, if you remove your testcles after puberty that would not save your hair. Yes it would, but you would probably not get significant regrowth since it is important for missing follicles to be exposed to estrogen, estradiol which is not the case when you do castration. Castration only decreases androgens to a level which is enough to cease future balding process.

It's not related to your post since you haven't said that, but I am curious are there any cases of people castrated after the onset of puberty who developed Androgenetic Alopecia ?

 

[waynakyo]

My question is: we know that DHT can induce hair loss in people who are prone to male pattern baldness. What is not clear is the process and I am talking from the perspective of TIME. When we were kids our DHT was on the roof, yet most were not balding yet

The standard answer was: The impact of DHT is a very gradua and cumulative process on the follicle. That sounds convincing...


... but, how come these people who reduce DHT suddenly within few weeks start having thicker hair...

...how come me and so many others have noticed that any activity/supplement that increase (reduce) DHT has had an impact on shedding within days...

... This forum is full of people who claim that increasing RU halted the shedding within days.. you might not want to believe them, but how about the people who grew tons of hair and had a thicker hair after few months of finasteride...

That does not seem to go well with the story that balding is the gradual and cumulative effect of DHT in male pattern baldness prone subjects...

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It seems to be more consistent with a threshold story, or some other process that correlates with DHT but happens to kick in later in life...

 

[Armando Jose]

I would like to read about this plenty of evidence that castration (chemical, or surgical), despite when it it has been done, halts or to be more precise slows down process of Androgenetic Alopecia to a level which can be considered to be negligible or stopped.

 

[uncomfortable man]

Lifelong pursuit is lifelong. You guys are going to be doing this **** when your eighty and still no cure.

 

[xRedStaRx]

I didn't want to use word activate to confuse you or other users, more appropriate word used in that context would be regulate. I marked a sentence in your quote which is important to understand; By that you mean there is a threshold. And when that threshold of androgen stimulus on AR is reached, chemical/molecular signals are sent by certain paths and mechanisms. If intensity of that stimulus is less than threshold then nothing would happen, and no signal and instructions would be sent to nucleus. So, only if stimulus is equal or bigger than threshold, chemical signals which regulates balding process/instructions of DP would be sent to nucleus. According to you statement hair follicle can be exposed to certain androgen stimulus for infinitely long time, but as long as that stimulus is less than critical threshold, nothing would happen ?



Can you please give answers on this questions:

Do you think when DHT binds to AR site that "stimulus" is more stronger compared to stimulus when T binds to the same receptor ?
Do you think that DHT (dihydro-testosterone) and T transmit different signals/instructions after binding to the same AR or their only difference is how successfully /effectively they bind to AR site ?




Well, in this thread he gave explanation why is castration more effective in halting male pattern baldness: http://www.hairlosstalk.com/interac...8-DHT-levels?p=1089252&viewfull=1#post1089252








I definitely agree with your statement conversion process depends on the amount of aromatase enzyme, SGBH, (FreeT, T, DHT) / E ratio and other factors. It's pretty much stochastic process and we must consider all hormones and enzymes which compete with each other in order to bind to AR.




I believe 5-ard activity increases as we age, in order to produce stronger androgen effect in target tissues. Benjt has proposed theory of DHT as hormone for local amplification of androgen effects, other endocrine experts share this theory. It would be logical to assume body produces 5ard to generate more potent derivative of testosterone - DHT to compensate lack of total T. And this makes sense.

What exactly you mean by signals from specific organs. Do you think that body produces same quantity of 5ard in scalp, for instance, but AR in DP cells, sebaceous glands become more sensitive in old age ? And because of that they produce more sebum and you can see many old slick bald guys have very oily scalp.





Can you please provide the link to that study ?

I think there is a plenty of evidence that castration (chemical, or surgical), despite when it it has been done, halts or to be more precise slows down process of Androgenetic Alopecia to a level which can be considered to be negligible or stopped. There are transsexual persons on oral spironolactone who do not loose hair, and even get decent regrowth.

The famous picture of "bald" chinese eunuch doesn't disprove this theory since the frontal loss of his hair might be because of several other reasons, after all exception doesn't always prove the rule, since there are lot more eunuchs who never went bald.

So, I think it is not correct to give statment, if you remove your testcles after puberty that would not save your hair. Yes it would, but you would probably not get significant regrowth since it is important for missing follicles to be exposed to estrogen, estradiol which is not the case when you do castration. Castration only decreases androgens to a level which is enough to cease future balding process.

It's not related to your post since you haven't said that, but I am curious are there any cases of people castrated after the onset of puberty who developed Androgenetic Alopecia ?

Your posts are a little long, but I'll still try to answer briefly. :jump:

There is no stimulus or threshold most probably that induces signals. Similar to androgenic hair, scalp hair experiences a reversal of growth through androgen exposure, unlike other types of hair on the body which get longer and heavier by androgens. Genetic factors determine both individual levels of androgen and the hair follicle's sensitivity to androgens. Now male pattern baldness, unlike some androgenic hair like arms and pubic area, is dimorphic, meaning that it is generally a sexually differentiated trait triggered through the type of 5-AR enzymes responsible for male sexual development. The evolutionary and genetic reason behind male pattern baldness in some individuals is not fully known, there might have been an evolutionary advantage towards men who went bald. On the other hand, it might not have been naturally selected because it posed no harm either way,

"According to you statement hair follicle can be exposed to certain androgen stimulus for infinitely long time, but as long as that stimulus is less than critical threshold, nothing would happen ?"

No, that's not what I meant. DHT is much more likely to bind to ARs on the dermal papilla, and stay there for a longer period of time, this cumulative androgenic exposure sets the course for progressive follicular miniaturization exclusive to mid-anterior regions of the scalp. Testosterone on the other hand, is an endocrine hormone, this is the main difference.

Do you think when DHT binds to AR site that "stimulus" is more stronger compared to stimulus when T binds to the same receptor ?

Yes, DHT is more androgenic than testosterone, and has more affinity towards AR binding.Do you think that DHT (dihydro-testosterone) and T transmit different signals/instructions after binding to the same AR or their only difference is how successfully /effectively they bind to AR site ?

No, they do not. They are both androgenic but with different potencies, see above.

What exactly you mean by signals from specific organs. Do you think that body produces same quantity of 5ard in scalp, for instance, but AR in DP cells, sebaceous glands become more sensitive in old age ? And because of that they produce more sebum and you can see many old slick bald guys have very oily scalp.

Androgen receptors normally get less ​sensitive as we age. On the other hand, the hair follicles would have been exposed to a higher volume of cumulative androgen exposure, coupled with oxidation and other aging and senescence processes, gives you male pattern baldness well into your 50s. Although it should not progress much after that.

Some organs are androgen intensive and need certain levels to function properly, they send autocrine/paracrine signals to stimulate 5-AR activity and increase tissue concentrations of DHT.

Can you please provide the link to that study ?

A simple Google search will show you plenty

http://www.ncbi.nlm.nih.gov/pubmed/9550125
http://joe.endocrinology-journals.org/content/162/3/341.full.pdf
http://www.ncbi.nlm.nih.gov/pubmed/19429451

But I am curious are there any cases of people castrated after the onset of puberty who developed Androgenetic Alopecia ?

Not that I'm aware of, no. It should be impossible to develop androgenic alopecia without much, if any testosterone.

 

[PreCueBall]

I've been wanting to ask a few questions regarding DHT and since it appears that the main educated hair loss gangsters on this site are posting in this thread, it seems like the right place to do it.

First off, how many of you are on finasteride? And if you are what have been your experiences with sides effects? I'm currently debating taking the plunge right now but am obviously terrified about having the sexual drive of a eunuch.

Has anyone tampered with anti-estrogens (either some hardcore **** or just natural onces such as Broccoli and Cauliflower) while taking finasteride? What would be the implications if both anti-DHT and anti-estrogens are being used at the same time? What would the Free T convert to and what would be the long term implications of this? I ask because it seems like the up in estrogen rather then the lack of DHT could be the main protagonist for a majority of the negative side effects associated with finasteride.

My last questions regards peoples experiences/opinions regarding black tea as a natural substitute for DHT inhibition. Apparently it reduced DHT by the same level as finasteride (assuming you take the converted amount of black tea which was used in the study group of mice, which I believe is 1.25 g/day for a human) which is around 70% but upped Total Test by 34% instead of finasteride's 10%.

My bad if I'm derailing the thread at all.

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Oh, and has anyone taken finasteride while on synthetic testosterone? Whether for practical purposes such as gaining muscle mass or to offset the side effects of finasteride.

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Lifelong pursuit is lifelong. You guys are going to be doing this **** when your eighty and still no cure.

Quit pooping on the party bro Rome wasn't built in a day.

 

[benjt]

I am not on finasteride. I am too young to risk anything in that field. I don't want systemic effects when only local effects are required and desired. Even if statistically the chances of side effects are around 7%, I am not willing to take that risk.

Thus, I also don't have any experiences with anti-estrogens. I assume, though, that when you lower both T->DHT and T->E conversion, that you will simply have more free T. As such, that would not lead to any negative side effects I could think of right now.

On the topic of black tea: Yes, it does work. I use it to get weaker DHT blocking than finasteride, and depending on how much I drink, I notice a decrease in libido. I try to drink "healthy" amounts around 3 to 4 pots a day, i.e. far away from the doses which are known to have prostate cancer risk increase (6 pots a day or something).

Total T increase, by the way, is neither a problem nor surprising. If less T is converted to DHT, of course more T will remain.

 

[drgs]

I use finasteride as "spot treatment" on the days of sex/masturbation, which for me averages to be 1-2 times per week.
I cannot prove or explain why, but personal experience has convinced me that the body produces more DHT with each ejaculation (I think primary because arousal/sex/orgasm raises T, considerably)

I was on finasteride for 4 months at first, had big positive effect on hair loss without a doubt, not so positive effects on my mental wellbeing, so I quit it, sort of, as described above

I've being doing it for 2 months, and my hair loss is still at halt, hasn't come back. It costs me about 1 proscar tablet a month

 

[PreCueBall]

I use finasteride as "spot treatment" on the days of sex/masturbation, which for me averages to be 1-2 times per week.
I cannot prove or explain why, but personal experience has convinced me that the body produces more DHT with each ejaculation (I think primary because arousal/sex/orgasm raises T, considerably)

I was on finasteride for 4 months at first, had big positive effect on hair loss without a doubt, not so positive effects on my mental wellbeing, so I quit it, sort of, as described above

I've being doing it for 2 months, and my hair loss is still at halt, hasn't come back. It costs me about 1 proscar tablet a month

That's interesting. I figure taking 1mg/day of the stuff is a bit of an overkill considering it keeps levels down for a couple days. So your basically taking 1mg of finasteride a week? My only concern with taking it like this would be the fluctuation in hormones causing hair loss.

 

[drgs]

That's interesting. I figure taking 1mg/day of the stuff is a bit of an overkill considering it keeps levels down for a couple days. So your basically taking 1mg of finasteride a week? My only concern with taking it like this would be the fluctuation in hormones causing hair loss.

Well, androgen hormones are not secreted evenly to begin with
Sex/ejaculation is one of the reasons for a testosterone spike, and the most common, I think.
In what other situations does it happen? I can think of heavy weightlifting, like squats etc (there are studies, however, days with heavy lifting are followed by a period of low T).
A period of low calorie diet with sudden switch to high calorie diet can trigger a rise in T and insulin
Certain social situations

finasteride serves for me as a reset button, sort of, whenever androgens get out of control, and I've learned to recognize when it happens

 

[benjt]

The thing is that sex/masturbation/ejaculation only increases systemic T and DHT, which has almost no effect at all on balding, since balding is a consequence of locally produced DHT in the scalp.

 

[PreCueBall]

This is gonna come out of left field but I'm hoping to get some insight on this since I can't find anything online about it. I've noticed the passed week that my Adams Apple is much larger and pointier then a few weeks ago? Its tripping me out because from what I understand is that it stops growing at the age of 18. Anyone think this has a relation to DHT?

Back on topic, if sex/masturbation/ejaculation increases systemic T and DHT and doesn't effect balding at all, then why does finasteride lower systemic DHT and have an effect on balding? The weird correlation with this and my pointier Adams Apple is that I gave up fapping for a solid 10 days (ended a few days ago).

 

[benjt]

Back on topic, if sex/masturbation/ejaculation increases systemic T and DHT and doesn't effect balding at all, then why does finasteride lower systemic DHT and have an effect on balding?

Because finasteride lowering systemic DHT is sort of a side effect. Primarily, it lowers 5ar all over the body. 5ar is the enzyme converting T do DHT. DHT exists as a certain base level (which is not remotely enough to "spill over" into the scalp to cause balding) systemically, but the real perpetrator is the local DHT in the scalp. Both are produced by 5ar (and thus, the production of both is hindered since finasteride blocks 5ar all over the body), but only the DHT in the scalp is the dangerous one, so to speak. Not because it is chemically in any way different from serum/systemic DHT, but simply because of its local availability and concentration. Systemic/serum DHT doesn't spill over in remotely sufficient amounts to the scalp.

 

[drgs]

The thing is that sex/masturbation/ejaculation only increases systemic T and DHT, which has almost no effect at all on balding, since balding is a consequence of locally produced DHT in the scalp.

From what is DHT converted locally in the scalp -- from systemic T or from local "scalp testosterone"?

 

[Armando Jose]

From local testosterone I suposse

 

[drgs]

Testosterone is produced in the skin of the scalp?
I know some testosterone is synthesized by the muscles, by thats as "local" as I can think of

 

[benjt]

Sorry, I was being unspecific. T is systemically produced and provided, but DHT is (for the most part) not.

 

[Armando Jose]

Testosterone is produced in the skin of the scalp?
I know some testosterone is synthesized by the muscles, by thats as "local" as I can think of

J Steroid Biochem Mol Biol. 2013 Sep;137:107-23. doi: 10.1016/j.jsbmb.2013.02.006. Epub 2013 Feb 19.
[h=1]Steroidogenesis in the skin: implications for local immune functions.[/h]Slominski A1, Zbytek B, Nikolakis G, Manna PR, Skobowiat C, Zmijewski M, Li W, Janjetovic Z, Postlethwaite A, Zouboulis CC, Tuckey RC.
[h=3]Author information[/h]

[h=3]Abstract[/h]The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7Δ-steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases. This article is part of a Special Issue entitled 'CSR 2013'.
http://www.ncbi.nlm.nih.gov/pubmed/23435015