Propecia and 5AR1
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hairrific
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I think your missing the target.
If I remember correctly finasteride lowers your serum dht to around 65-70-% and 32% locally at the scalp follicles where you really need it to be lowered.
Just because there is around a 15% increase in T, it does not mean more will be converted to DHT. The body needs 2 or 3 days to make more 5AR for the conversion of T to DHT and it cannot do so because you keep popping that crazy little pill every day.
5AR type 1 seems to have little effect on hair loss, compared to 5AR type 2. dutasteride does give better results but probably mostly because of greater reduced 5AR type 2 over finasteride and also the reduced 5AR 1 may be a secondary factor why dutasteride is more effective.
If I remember correctly finasteride lowers your serum dht to around 65-70-% and 32% locally at the scalp follicles where you really need it to be lowered.
Just because there is around a 15% increase in T, it does not mean more will be converted to DHT. The body needs 2 or 3 days to make more 5AR for the conversion of T to DHT and it cannot do so because you keep popping that crazy little pill every day.
5AR type 1 seems to have little effect on hair loss, compared to 5AR type 2. dutasteride does give better results but probably mostly because of greater reduced 5AR type 2 over finasteride and also the reduced 5AR 1 may be a secondary factor why dutasteride is more effective.
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JohnNYC said:
What "hairrific" said below you is correct: 5a-reductase type 1 activity is only very weakly associated with hair loss, so don't lose any sleep over a very slight increase in its activity!
It's greatly overshadowed by the inhibition of type 2 by finasteride. Type 2 activity is STRONGLY associated with hair loss.Bryan said:JohnNYC said:
What "hairrific" said below you is correct: 5a-reductase type 1 activity is only very weakly associated with hair loss, so don't lose any sleep over a very slight increase in its activity!
I am not so sure this is true. Let me dig up an interesting paper I saw on the subject.
Certainly, my own experience with Finasteride and Dutasteride supports my position.
The importance of dual 5a-reductase inhibition in the treatment of male pattern hair loss: Results of a randomized placebo-controlled study of dutasteride versus finasteride
Elise A. Olsen, MD,a Maria Hordinsky, MD,b David Whiting, PhD,c Dow Stough, MD,d Stuart Hobbs, PharmD,e Melissa L. Ellis, PharmD,e Timothy Wilson, MS,e and Roger S. Rittmaster, MD,e for the Dutasteride Alopecia Research Team* Durham and Research Triangle Park, North Carolina; Minneapolis, Minnesota; Dallas, Texas; and Hot Springs, Arkansas
"In conclusion, 2.5-mg dutasteride, a dual 5a- reductase inhibitor, improved hair growth in balding men more rapidly and to a greater degree than finasteride, a selective type 2 inhibitor. Dutasteride was generally well tolerated. The results of this study demonstrate the significant additive effect of inhibit- ing both type 1 and type 2 5a-reductase in the treatment of MPHL."
http://www.hairstransplanted.com/articl ... n_MPHL.pdf
Elise A. Olsen, MD,a Maria Hordinsky, MD,b David Whiting, PhD,c Dow Stough, MD,d Stuart Hobbs, PharmD,e Melissa L. Ellis, PharmD,e Timothy Wilson, MS,e and Roger S. Rittmaster, MD,e for the Dutasteride Alopecia Research Team* Durham and Research Triangle Park, North Carolina; Minneapolis, Minnesota; Dallas, Texas; and Hot Springs, Arkansas
"In conclusion, 2.5-mg dutasteride, a dual 5a- reductase inhibitor, improved hair growth in balding men more rapidly and to a greater degree than finasteride, a selective type 2 inhibitor. Dutasteride was generally well tolerated. The results of this study demonstrate the significant additive effect of inhibit- ing both type 1 and type 2 5a-reductase in the treatment of MPHL."
http://www.hairstransplanted.com/articl ... n_MPHL.pdf
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JohnNYC said:
The title of that recent study shows that they were mainly just speaking "off the top of their heads". That title wasn't a very serious scientific evaluation.
Besides finasteride (a specific type 2 inhibitor), Merck also developed a drug they call "MK386", which is a very specific 5a-reductase type 1 inhibitor. There have been several studies on MK386, including one on its use with balding stumptailed macaques, which showed that there was no noticeable effect; that contrasts sharply with earlier studies of finasteride with stumptailed macaques, which showed the same beneficial effect on those monkeys that it does with humans. Furthermore, Merck did an early, unpublished trial of MK386 with humans, showing (again) no effect on hair loss.
It's been well-established over the years that 5a-reductase type 1 inhibition has relatively little effect on androgenetic alopecia. The superiority of dutasteride over finasteride for that purpose is mostly because of the fact that dutasteride inhibits the type 2 enzyme more completely than finasteride (about 98%-99% by dutasteride, compared to only about 85%-90% by finasteride).
I am not saying that type 1 is more responsible. Nor am I saying type 1 inhibition alone will have any effect. I am saying that so some, inhibition of both are required. This has been my experience and that view is also supported by Dr. C at the u of PA
Bryan said:
That is interesting... how come this is so? Why does a drug need to block type 1 5AR in order to block more of type 2 5AR?
Why can't finasteride or dutasteride be formulated in a way that blocks 98%-99% of type 2 5AR without blocking type 1 5AR?
I guess I'm just wondering if it is POSSIBLE for a drug to block 99% of 5AR2 alone, or if there is some reason that this can't be achieved...
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revolt said:
It DOESN'T need to do that! The numbers I cited are just the ones for finasteride and dutasteride specifically.
revolt said:
If you altered their chemical structures in some way so that they'd block more 2 5AR, they would no longer be finasteride or dutasteride!
revolt said:
Sure, that can be achieved. But it would be a different drug!
Thanks for all the feedback everyone. I remember reading somewhere that 5AR2 accounts for about 70% of serum DHT and and the rest comes from 5AR1. So if a high percentage of 5AR2 is being inhibited systemically then then systemic T levels increase as a result. This increase in systemic T means there is more of a chance that they will bind to 5AR1 and convert to DHT locally within the hair hair follicle thus leading to a hypothetical increase of activity at this 5AR1 site (again, I cannot recall what specific part of scalp hair contains 5AR1 and 5AR2). But I would also like to point out that I've read that heavy cardio can increase T binding to the SHBG and reduces free T in the blood which will lead to less DHT!
A new thought occurred to me when I was reading going through a forum one day. Someone cited a study that showed that T injections and DHT injections led to hair loss (can't remember if rats or humans, but most likely rats). Anyone else seen or heard of this? Because I thought castrated men or men born without 5AR do not experience male pattern baldness all the while experiencing normal T levels.
thank you
A new thought occurred to me when I was reading going through a forum one day. Someone cited a study that showed that T injections and DHT injections led to hair loss (can't remember if rats or humans, but most likely rats). Anyone else seen or heard of this? Because I thought castrated men or men born without 5AR do not experience male pattern baldness all the while experiencing normal T levels.
thank you
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kumarhk said:
Happle & Hoffman found that the dermal papilla (the "nerve center" of the hair follicle) seems to contain almost entirely type 2 5a-reductase. There may be some type 1 in other areas of the follicle.
kumarhk said:
If you do something to increase the production of SHBG in the bloodstream, don't you think your body would simply make more testosterone as a result? Don't you know that the body notices little things like how much available testosterone there is in the bloodstream?? :dunno:
kumarhk said:
Do you really think rats have androgenetic alopecia?
kumarhk said:
Most of the damage done to hair follicles by DHT comes about from DHT that's generated INSIDE hair follicles; nevertheless, I don't think anybody would find it very prudent to go injecting DHT into your blood!
Quantum Cat
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interesting thread. One of the reasons I would be wary of taking Dutasteride is because it unnecessarily inhibits Type I, which apparently has no role in male pattern baldness.
A drug that inhibited all of Type II but only Type II sounds like it would be ideal.
A drug that inhibited all of Type II but only Type II sounds like it would be ideal.
ladysmanfelpz
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You guys got it all wrong. I think i've told you this before quantum. It is the type I that plays a larger role in male pattern baldness. I did a huge undergraduate research project on this stuff and I concluded its more type I. Have you noticed that all guys with thick hair also have very clear skin? Its because they have a low 5AR I. Type I dht is found predominantly in the hair follicles of our face and skin. In one study in my project on BPH, they clearly stated that patients on dutasteride had the added benefit of hair REGROWTH due to the inhibition of type I dht. Type II dht is the hormone involved in all sexual development and sexual activity, so complete inhibition of that is the stupidest idea ever. Inhibition of type I by 70% and type II by 30-50% percent I believe would be the ideal medication. I do believe both forms of dht play a role in male pattern baldness but type I more since it acts directly on the hair follicle. All I know is I had terrible acne and crazy oily face as well as my hair loss that started at 17 and only continued to get worse. See teenagers have the oily face and acne because their DHT levels have increased so the body sexually develops correctly. I however didn't grow out of this stage and my acne kept getting worse until it reached its peak at about 21 and my hairloss was the worst it had been as well. I started finasteride and it stopped my hairloss completely, but did not do anything for my acne or greasy face. I started dutasteride and it cleared me right up. Within a week I was clear. My skin feels better the more I dose as it inhibits more of type I with greater dose, even though it does not have much more of an affect on type II at higher doses. Now acne is a thing of the past for me and I'm finally getting regrowth after about being 3 months on dutasteride.
Quantum Cat
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yet you're taking Dutasteride which inhibits practically all Type II. If you think it's the stupidest idea ever why are you doing it?
In theory, DHT isn't supposed to have any essential role in the ADULT body, which is why DHT blockers were greenlit as an acceptable drug to use. Obviously that's been much debated on here, but I think that's the current accepted scientific position. Despite the small but vocal claims of side effects from finasteride, many men take finasteride and have no sexual problems at all - so suppressing 65% of Type II doesn't appear to matter.
as for your theory that Type I has the greater role in male pattern baldness, publish it, and if it gets peer reviewed and is accepted by the scientific community, you'll have contributed to our understanding of male pattern baldness.
ladysmanfelpz
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I posted this yesterday but for some reason it didn't go through.
"The key enzyme in the formation of DHT is steroid 5α-reductase. It is present throughout the body in two forms, type 1 and type 2, which are encoded by the genes SRD5A1 and SRD5A2, respectively [4]. The type 2 5α-reductase is the predominant isozyme in the male accessory sex glands and in the prostate, including benign prostatic hyperplasia and prostate adenocarcinoma tissues, whereas the type 1 isozyme predominates in skin [5]. Both forms are expressed in the liver. Finasteride was the first available 5α-reductase inhibitor and is selective for the type 2 isoenzyme [6]. Its clinical utility in relieving symptoms associated with benign prostatic hyperplasia (BPH) has been well documented in several clinical trials. In addition, finasteride was tested as a potential chemopreventive agent in the prostate cancer prevention trial[7]. A second 5α-reductase inhibitor, namely dutasteride, became available for treatment of BPH. It inhibits both types of 5α-reductases and suppresses serum DHT levels to a greater extent than finasteride [8]. However, whether there is a clinical difference between the two inhibitors has not been established."
Citation: Stanczyk, F. Z., Azen, C. G., & Pike, M. C. (2013). Effect of finasteride on serum levels of androstenedione, testosterone and their 5alpha-reduced metabolites in men at risk for prostate cancer. The Journal of Steroid Biochemistry and Molecular Biology,
"Type II 5α-reductase is the predominant isozyme in the human prostate and is targeted by Finasteride, which decreased prostate size by 25% on average in men with BPH, improved LUTS, and increased urinary flow rates (Kaplan et al., 2008). Another 5α-reductase inhibitor, Dutasteride, inhibits 5α-reductase types I and II; because type I 5α-reductase is the predominant isozyme in the hair follicle it has the added benefit of increasing hair growth in male pattern hair loss (Olsen et al., 2006). Less is known about 5α-reductase type III but it may also participate in prostatic proliferation because it is expressed in prostate cancers (Uemura et al., 2008). "
Citation: Nicholson, T. M., & Ricke, W. A. (2011). Androgens and estrogens in benign prostatic hyperplasia: Past, present and future. Differentiation; Research in Biological Diversity, 82(4-5), 184-199.
And this study done by Bernstein Medical shows the significance of type 1 reduction.
In a test area at 24 weeks, results showed:
See as you can see hair growth is dose dependent with dutasteride. Even tho the inhibition of serum DHT from prescribed dose (.5mg at 92% reduction) to a higher dose (2.5 mg at 96% reduction) is marginal, the gains in hair regrowth is significant. This is done by the inhibition of more type 1 enzyme which is difficult. Low dose dutasteride had more regrowth than finasteride even tho finasteride lowered serum level more (32% .1mg dutasteride compared to 40% at 5 mg finasteride).
I am taking cut up dutasteride Quantum so roughly over a tenth of a mg. I was on finasteride for about 4-5 months and it didn't do **** for my skin. Got on dutasteride and my skin cleared up in a week. I am finally getting results so hopefully soon I will post a thread in the success forum explaining my program and the reasoning behind it.
"The key enzyme in the formation of DHT is steroid 5α-reductase. It is present throughout the body in two forms, type 1 and type 2, which are encoded by the genes SRD5A1 and SRD5A2, respectively [4]. The type 2 5α-reductase is the predominant isozyme in the male accessory sex glands and in the prostate, including benign prostatic hyperplasia and prostate adenocarcinoma tissues, whereas the type 1 isozyme predominates in skin [5]. Both forms are expressed in the liver. Finasteride was the first available 5α-reductase inhibitor and is selective for the type 2 isoenzyme [6]. Its clinical utility in relieving symptoms associated with benign prostatic hyperplasia (BPH) has been well documented in several clinical trials. In addition, finasteride was tested as a potential chemopreventive agent in the prostate cancer prevention trial[7]. A second 5α-reductase inhibitor, namely dutasteride, became available for treatment of BPH. It inhibits both types of 5α-reductases and suppresses serum DHT levels to a greater extent than finasteride [8]. However, whether there is a clinical difference between the two inhibitors has not been established."
Citation: Stanczyk, F. Z., Azen, C. G., & Pike, M. C. (2013). Effect of finasteride on serum levels of androstenedione, testosterone and their 5alpha-reduced metabolites in men at risk for prostate cancer. The Journal of Steroid Biochemistry and Molecular Biology,
"Type II 5α-reductase is the predominant isozyme in the human prostate and is targeted by Finasteride, which decreased prostate size by 25% on average in men with BPH, improved LUTS, and increased urinary flow rates (Kaplan et al., 2008). Another 5α-reductase inhibitor, Dutasteride, inhibits 5α-reductase types I and II; because type I 5α-reductase is the predominant isozyme in the hair follicle it has the added benefit of increasing hair growth in male pattern hair loss (Olsen et al., 2006). Less is known about 5α-reductase type III but it may also participate in prostatic proliferation because it is expressed in prostate cancers (Uemura et al., 2008). "
Citation: Nicholson, T. M., & Ricke, W. A. (2011). Androgens and estrogens in benign prostatic hyperplasia: Past, present and future. Differentiation; Research in Biological Diversity, 82(4-5), 184-199.
And this study done by Bernstein Medical shows the significance of type 1 reduction.
In a test area at 24 weeks, results showed:
| Placebo | -32.3 hairs |
| Finasteride 5mg | 75.6 hairs |
| Dutasteride 0.1 mg | 78.5 hairs |
| Dutasteride 0.5 mg | 94.6 hairs |
| Dutasteride 2.5 mg | 109.6 hairs |
I am taking cut up dutasteride Quantum so roughly over a tenth of a mg. I was on finasteride for about 4-5 months and it didn't do **** for my skin. Got on dutasteride and my skin cleared up in a week. I am finally getting results so hopefully soon I will post a thread in the success forum explaining my program and the reasoning behind it.