Quick Question - Dht Inhibition. Not Important:)

[Throwaway94]

Right okay now that makes a lot more sense! I think I forgot to factor in the difference of enzymes (type 1,2 & 3). So just to clarify on your very last statement.. would the remaining 60% of scalp dht concentration left behind be all type 1? And if so, do we know for certain that type 2 is doing all the damage? Very informative thanku

It's mostly type 1 that's produced in the sebaceous glands and type 2 that's produced locally in the hair follicle. We don't know for sure that type 2 is doing all the damage, as I'm positive that not all DHT produced in the sebaceous gland is consumed by that gland and some will venture over to the hair follicle, but realistically the biggest dent in relevant scalp DHT you can make is by type 2 inhibition.

 

[SausageDawg]

What I said was actually pretty dumb since the same enzyme responsible for DHT is responsible for all the neurosteroids so they should be affected the same way, I'm just thinking that maybe there's a difference for the isoenzyme that finasteride also covers that might differ. Absolutely agree though the lowest dose is safer.

Ah okay I see, sorry to pick your brains on this but do you have any hypothesis on why the guevedoces dont seem to experience any symptoms of neurosteroid deprivation? If I'm correct in saying they're are absent of the 5ar enzyme yet from all the footage/stories I've seen.. in fact they generally seem like a healthy population! I can never wrap my head round that one lol

 

[Throwaway94]

Ah okay I see, sorry to pick your brains on this but do you have any hypothesis on why the guevedoces dont seem to experience any symptoms of neurosteroid deprivation? If I'm correct in saying they're are absent of the 5ar enzyme yet from all the footage/stories I've seen.. in fact they generally seem like a healthy population! I can never wrap my head round that one lol

Lol I had to Google guevedoces. They appear to be deficient in type 2 only - best I can come up with right now is that the tissue in which 5-ar2 is expressed isn't critical in the role of cognitive development. Type 1 is more abundant in the brain whereas type 2 seems limited mostly to the prostate / genitals / I suppose hair follicles too

Absolutely just spitballing here though (AKA talking sh*t) since I didn't get anything from any study besides the isoenzyme distribution across tissues.

 

[SausageDawg]

Lol I had to Google guevedoces. They appear to be deficient in type 2 only - best I can come up with right now is that the tissue in which 5-ar2 is expressed isn't critical in the role of cognitive development. Type 1 is more abundant in the brain whereas type 2 seems limited mostly to the prostate / genitals / I suppose hair follicles too

Absolutely just spitballing here though (AKA talking sh*t) since I didn't get anything from any study besides the isoenzyme distribution across tissues.

Haha mate you've explained so much dont even worry about it!! Dont expect you to know everything ever;-) the guevedoces thing always plays havoc with my brain when people mention the neuro-steriods issue or even the pfs sufferers who complain of total erectile dysfunction.. despite boys castrated before puberty can still achieve erections. They're seems to be so many examples of healthy life without dht yet it clearly causes issues when inhibited!

 

[Throwaway94]

Haha mate you've explained so much dont even worry about it!! Dont expect you to know everything ever;-) the guevedoces thing always plays havoc with my brain when people mention the neuro-steriods issue or even the pfs sufferers who complain of total erectile dysfunction.. despite boys castrated before puberty can still achieve erections. They're seems to be so many examples of healthy life without dht yet it clearly causes issues when inhibited!

Honestly man, I think the PFS thing is overblown. I'm sure there are people with lasting side effects but this whole "I was fine before but now I'm suicidal and am completely 100% unable to get a boner" thing is pretty unrealistic.

Can it exacerbate existing depression? Maybe but that could also be caused by the progression of hair loss that you feel you can't treat anymore. Can it cause lasting erection problems? Maybe but so can depression, and so can psyching yourself out because you think you can't perform because of medication.

 

[AndrewBarnes]

According to the first study I found on Google, Finasteride decreases Scalp DHT by up to 70%.

Results: Scalp skin DHT levels declined significantly by 13.0% with placebo and by 14.9%, 61.6%, 56. 5%, 64.1%, and 69.4% with 0.01, 0.05, 0.2, 1, and 5 mg doses of finasteride, respectively. Serum DHT levels declined significantly (P <.001) by 49.5%, 68.6%, 71.4%, and 72.2% in the 0.05, 0.2, 1, and 5 mg finasteride treatment groups, respectively.

https://pubmed.ncbi.nlm.nih.gov/10495374/

 

[Selb]

Well the question is how much does this vary? Maybe reduction of scalp dht isn’t effective for a lot of people with oral finasteride. That’s why using topical finasteride alongside oral finasteride might actually be effective at reducing scalp dht enough to halt hair loss

 

[Gold24]

One thing also to consider which has kinda already been alluded to here is actual ‘follicular DHT’ which is the actual DHT at the hair follicle.

Bryan who was one of the most knowledgable guys on this forum was very interested in this subject. In some thread he mentioned that ‘scalp DHT’ is irrelevant because it is a measure of DHT around different areas of your scalp not just the hair follicle. If I remember correctly he actually estimated that finasteride actually inhibited roughly around 85% of ‘follicular DHT’. That is DHT which is present at the hair follicle. I could try dig up the discussion but it might take a while since it’s quite an old one.

 

[Rudolphus]

One thing also to consider which has kinda already been alluded to here is actual ‘follicular DHT’ which is the actual DHT at the hair follicle.

Bryan who was one of the most knowledgable guys on this forum was very interested in this subject. In some thread he mentioned that ‘scalp DHT’ is irrelevant because it is a measure of DHT around different areas of your scalp not just the hair follicle. If I remember correctly he actually estimated that finasteride actually inhibited roughly around 85% of ‘follicular DHT’. That is DHT which is present at the hair follicle. I could try dig up the discussion but it might take a while since it’s quite an old one.

Exactly! I've been looking through some of Bryan's old posts about this subject, and it is correct that follicular DHT is what matters most in male pattern baldness. Specifically, it is the DHT within the dermal papillae of the hair follicles that is primarily responsible. The 5AR within the dermal papillae has been shown to consist almost entirely of 5AR type 2 (of which finasteride is a selective inhibitor). Finasteride was found to very potently inhibit this 5AR within the dermal papillae, which explains why finasteride works so well for hair loss.

I've pasted below an excellent post about this subject by Bryan in an old thread:

"For a long time there's been conflicting information about which type of 5a-reductase occurs in human hair follicle cells. Some earlier studies claimed to find large amounts of the type 1 enzyme, with little or no type 2 at all. Then along came a study by Happle and Hoffmann (1) which seemed to find type 2 almost EXCLUSIVELY within dermal papilla cells. So how does that jive with those ealier studies? One possible clue is that Happle & Hoffman used freshly dissected hair follicles. They went to work on them as soon as they were extracted from their human test subjects! Under those specific conditions, they found that finasteride was BY FAR the main inhibitor of 5a-reductase activity within those hair follicle cells.

The final key to the puzzle, in my opinion, was published in a Japanese study a couple of years after that (2). They found that 5a-reductase type 2 activity in hair follicles evidently is lost fairly quickly when cultured in vitro, but is normally present in vivo. So the bottom-line to all this is that if you do an in vitro study of human hair follicles and add testosterone to them to see how it affects their growth rate, the observed suppression MAY be due more to the direct effect of the testosterone, because less and less of it is being converted into DHT as time goes by.

(1) "Finasteride is the main inhibitor of 5a-reductase activity in microdissected dermal papillae of human hair follicles", Hoffmann and Happle, Arch Dermatol Res (1999) 291: 100-103.

(2) "5-Reductase type 2 is constitutively expressed in the dermal papilla and connective tissue sheath of the hair follicle in vivo but not during culture in vitro", Asada et al, J Clin Endocrinol Metab 86: 2875-2880, 2001.

Bryan"


For your interest, here is the thread: https://www.hairlosstalk.com/interact/threads/dht-and-testosterone-kills-hair-directly-study.22820/

 

[Norwoody]

So in your opinion Rudolphus, does this mean that we should strive to use 5ARIs topically?

 

[Rudolphus]

So in your opinion Rudolphus, does this mean that we should strive to use 5ARIs topically?

Yes, I would say so, but it is easier said than done in terms of getting the desired effect. Ideally, we need to remove as much DHT within the hair follicles as we can while removing as little systemic DHT as we can. Topical finasteride has a tendency to go systemic. I've heard that topical dutasteride is less likely to go systemic, especially when used in certain formulations such as liposomal. There are anecdotal reports on these forums of people who claim to have got regrowth on topical dutasteride without any of it going systemic (confirmed by blood tests). However, further research is needed to support these anecdotes. I'd like to see a study done on topical finasteride (or topical dutasteride) that compares the amount of DHT suppression within the dermal papillae of the hair follicles with the amount of DHT suppression in the blood serum. Such a study would really be putting the usefulness of topical 5AR inhibitors to the test. It might not be easy to perform such a study though, unfortunately. Without research of this kind, we basically have to rely on a fair amount of guesswork.

 

[bluecyclone]

How are people able to get Scalp DHT measured?

 

[Gold24]

Exactly! I've been looking through some of Bryan's old posts about this subject, and it is correct that follicular DHT is what matters most in male pattern baldness. Specifically, it is the DHT within the dermal papillae of the hair follicles that is primarily responsible. The 5AR within the dermal papillae has been shown to consist almost entirely of 5AR type 2 (of which finasteride is a selective inhibitor). Finasteride was found to very potently inhibit this 5AR within the dermal papillae, which explains why finasteride works so well for hair loss.

I've pasted below an excellent post about this subject by Bryan in an old thread:

"For a long time there's been conflicting information about which type of 5a-reductase occurs in human hair follicle cells. Some earlier studies claimed to find large amounts of the type 1 enzyme, with little or no type 2 at all. Then along came a study by Happle and Hoffmann (1) which seemed to find type 2 almost EXCLUSIVELY within dermal papilla cells. So how does that jive with those ealier studies? One possible clue is that Happle & Hoffman used freshly dissected hair follicles. They went to work on them as soon as they were extracted from their human test subjects! Under those specific conditions, they found that finasteride was BY FAR the main inhibitor of 5a-reductase activity within those hair follicle cells.

The final key to the puzzle, in my opinion, was published in a Japanese study a couple of years after that (2). They found that 5a-reductase type 2 activity in hair follicles evidently is lost fairly quickly when cultured in vitro, but is normally present in vivo. So the bottom-line to all this is that if you do an in vitro study of human hair follicles and add testosterone to them to see how it affects their growth rate, the observed suppression MAY be due more to the direct effect of the testosterone, because less and less of it is being converted into DHT as time goes by.

(1) "Finasteride is the main inhibitor of 5a-reductase activity in microdissected dermal papillae of human hair follicles", Hoffmann and Happle, Arch Dermatol Res (1999) 291: 100-103.

(2) "5-Reductase type 2 is constitutively expressed in the dermal papilla and connective tissue sheath of the hair follicle in vivo but not during culture in vitro", Asada et al, J Clin Endocrinol Metab 86: 2875-2880, 2001.

Bryan"


For your interest, here is the thread: https://www.hairlosstalk.com/interact/threads/dht-and-testosterone-kills-hair-directly-study.22820/

Very interesting stuff. Thanks for this.

 

[rapper dude]

How are people able to get Scalp DHT measured?

? DOES ANYONE KNOW

 

[Gold24]

? DOES ANYONE KNOW

It’s called a scalp biopsy. I believe a small bit of skin is removed from the scalp and examined.