Why dutasteride may not work as good as finasteride in some people

[Jack]

I was having a look at the dutasteride phase 2 results again at
http://www.regrowth.com/hairloss-remedy ... esults.cfm
and some thoughts accured to me when I read that 0.5mg dutasteride increased free Testosteron by 27% (and 104% for so called scalp test.) but 5mg finasteride only increased it by 4.4% (+24% scalp ):

1. This larger increase in Test. in the dutasteride-group results from its unique DHT type 1 reduction. There is far more DHT type 1 produced in the follicles than dht type 2, and because 50% of these are inhibited , testosterone levels rise considerable. DHT type 2 exists only in much smaller quantities (but is MUCH worse for hair) and therefore finasteride increases test only slightly.

2. I was searching in the forum and found out that both Testosterone and DHT type 1 are bad for hair , but I'm unsure which is worse - the dutasteride trials clearly indicate that dht type I is worse, but I was thinking that maybe for some people test is more of a problem than dht type 1 ...the trial was rather small , with only about 110 people using 0.5mg and more dutasteride a day .

SO the ranking for hair killers is as follows :
1. DHT type 2 by a large margin.
2. DHT type 1
3. testosterone
With 2. and 3. beeing supposly interchangeable for some people ?
I know the studies clearly contradict this , and Every test molecule which isn't converted to DHT is supposed to be a HUGE success for Hairloss prevention but I'm still not satisfied on the DHT I vs Testosteron question ..

 

[Nighthair]

I am just talking out of my *** here but i think it could be that too much DHT can cause baldness but too little DHT can also damage hair. Maybe in order to have a full head of hair, we need a "just-right" amount?

 

[OverMachoGrande]

I am just talking out of my *** here but i think it could be that too much DHT can cause baldness but too little DHT can also damage hair. Maybe in order to have a full head of hair, we need a "just-right" amount?

Actually I sort of agree with this statement. I tried 2.5 mgs of dutasteride for awhile and it definitely made things worse, I scaled back to 1 dutasteride per week and things got better.

 

[Jack]

I am just talking out of my *** here but i think it could be that too much DHT can cause baldness but too little DHT can also damage hair. Maybe in order to have a full head of hair, we need a "just-right" amount?

Yes my 2nd theory was similiar to yours - as in : Too much DHT inhibition causes reflex hyperandrogenity and makes matters worse..
But again , there are no studies which indicate this , not even the long time 5years+ avodart studies for BPH showed increased hyperandrogenity.
Avodart is not THAT strong , it's not a true anti-androgen like flutamide which is known for the hyperangrogenity it causes.
Even if there is some upregulation - meaning increased number of androgen receptors - the dht inhibition should still protect the hair due to the dht inhibition.

 

[hairrific]

QUOTE:
Although the rise in Testosterone may seem high, the Testosterone levels were almost always within normal range according to Rittmaster.

Is he talking about scalp testosterone or in the blood?

I was under the impression type I has little effect on scalp hair and is not predominate there.

 

[Mew]

The reason why is because both drugs affect the 5AR enzymes differently, and researchers are calling on GENOTYPING men PRIOR to therapy to determine which drug would be the better choice in terms of response.

http://jme.endocrinology-journals.org/c ... l/34/3/617
http://www.propeciahelp.com/forum/viewtopic.php?t=1407

The Androgen Receptor is also involved, in terms of CAG triplet repeat length, which also determines response to Finasteride. There is now a test you can take before starting the drug to determine your potential response to it:
http://www.hairdx.com

 

[Jack]

Hmm the FAQ on this site only states that the gene test will tell you if you have a high chance of balding or not balding ...how does it tell you if avodart or finasteride works better?
I already know I'm balding , don't need such tests.

 

[Jack]

Nevermind , I just had a closer look at this site and they offer a specific finasteride response test . Too bad they don't compare it to dutasteride , which makes this test pretty much useless .......if you fail the test , there is no guarantee that dutasteride works any better , or infact worse than finasteride.

On the other hand the studies you provides came up with this conclusion :

In summary, our systematic analysis of both constitutional and somatic (prostate cancer) variants of steroid 5-reductase type II indicates that dutasteride is a more efficient steroid 5-reductase type II inhibitor than finasteride in vitro for most of the enzyme variants, and that dutasteride treatment is also expected to result in lower pharmacogenetic variation in vivo than finasteride treatment. However, the pharmacogenetic variation we uncovered for both finasteride and dutasteride is still very significant and this should be taken into account when designing protocols for treatment and/or chemoprevention of prostatic diseases with either one of these drugs.

Which contradicts these anecdotes on here that finasteride is a safer bet than dutasteride , because there are alot of fail-stories here with dutasteride.(and these people had unsuccessful treatment prior with finasteride ...).

Yeah , after reading these studies the genotype variation thing seems far more plausible than the testostorone or the hyperandrogenity theories :agree:

I may consider switching if I have unfavoreable dutasteride results after 12 months .

 

[Bryan]

1. This larger increase in Test. in the dutasteride-group results from its unique DHT type 1 reduction. There is far more DHT type 1 produced in the follicles than dht type 2, and because 50% of these are inhibited , testosterone levels rise considerable. DHT type 2 exists only in much smaller quantities (but is MUCH worse for hair) and therefore finasteride increases test only slightly.

Actually, the larger increase in testosterone is undoubtedly caused by a combination of the partial type 1 inhibition AND a more complete inhibition of type 2.

I don't know where you got your information that there is "far more DHT type 1" in hair follicles than type 2, but I find that claim rather speculative. There have been conflicting studies on the distribution of those enzymes in the whole structure of hair follicles, and I think we simply don't know for sure what their relative activites are. In the all-important dermal papilla, though, it now seems clear that the type 2 enzyme predominates, which explains why finasteride works and MK386 doesn't.

 

[Bryan]

I am just talking out of my *** here but i think it could be that too much DHT can cause baldness but too little DHT can also damage hair. Maybe in order to have a full head of hair, we need a "just-right" amount?

How do you explain people with CAIS (Complete Androgen Insensitivty Syndrome), who have great hair? They have mutated, non-functional androgen receptors, and get no androgenic stimulation at all.

 

[Jack]

I don't know where you got your information that there is "far more DHT type 1" in hair follicles than type 2, but I find that claim rather speculative.

I got it from the quoted article , specifically :

Scalp DHT measurements were also assessed for both DHT and Testosterone. Scalp DHT was decreased 27% for 0.05mg Dutasteride, similarly for Finasteride (38%) and Dutasteride 0.1mg (37%), 54% for 0.5mg, and 82% for 2.5mg Dutasteride. Rittmaster concluded that these results show that most of the DHT in the scalp comes from type 1 5-alpha reductase.

I know people don't like the term scalp dht , but I figured that blood testosterone or scalp testosterone have to reflect the percentages somehow .

Also if you compare the Test. % between 0.1mg dutasteride and 5mg finasteride , you have to wonder where this large difference in testosterone comes from

Testosterone increased 4.4% for Finasteride, 6.4% for 0.05mg Dutasteride, 16% for 0.1mg Dutasteride,

considering that 0.1mg dutasteride has similiar DHT type II reduction compared to finasteride and only slight dht type I reduction I would have expected the numbers to be closer together.
This is why i concluded that the total dht type I quantities must be much higher , but I see my error of thinking now - there is no evidence of how much of this DHT type I is produced in the follicle itself :woot:

 

[Bryan]

I don't know where you got your information that there is "far more DHT type 1" in hair follicles than type 2, but I find that claim rather speculative.

I got it from the quoted article , specifically :

Scalp DHT measurements were also assessed for both DHT and Testosterone. Scalp DHT was decreased 27% for 0.05mg Dutasteride, similarly for Finasteride (38%) and Dutasteride 0.1mg (37%), 54% for 0.5mg, and 82% for 2.5mg Dutasteride. Rittmaster concluded that these results show that most of the DHT in the scalp comes from type 1 5-alpha reductase.

Yes, but that's referring to the whole SCALP, not HAIR FOLLICLES specifically. The "scalp" includes sebaceous glands, which are rich in the 5a-reductase type 1 enzyme. This is exactly why I don't like the use of the word "scalp" when talking about hair problems: it's too easy to confuse sebaceous gland issues with hair follicle issues!!

I know people don't like the term scalp dht , but I figured that blood testosterone or scalp testosterone have to reflect the percentages somehow .

Not consistently enough to be useful for our purposes.

Also if you compare the Test. % between 0.1mg dutasteride and 5mg finasteride , you have to wonder where this large difference in testosterone comes from

Testosterone increased 4.4% for Finasteride, 6.4% for 0.05mg Dutasteride, 16% for 0.1mg Dutasteride,

considering that 0.1mg dutasteride has similiar DHT type II reduction compared to finasteride and only slight dht type I reduction I would have expected the numbers to be closer together.

Where did those numbers come from? The same source as the other quote? Personally, I take numbers like that with a grain or two of salt, because there's inconsistency even in studies reporting testosterone increases for the SAME drug (like finasdteride). Sometimes it's almost nothing, other times it's more substantial like 10% to 15%. Those numbers vary so much for reasons I don't fully understand (part of it may have to do with the difficulty and unreliability of measuring testosterone and DHT in tissue samples and biopsies), I really don't think they're particularly useful for anything.

 

[Jack]

I got the numbers from http://www.regrowth.com/hairloss-remedy ... esults.cfm , which cites Rittmaster at the American Academy of Dermatology (AAD) meeting who was presenting the Phase II results.

Normally I also would just think these are normale insignificant hormone fluctuations , BUT these numbers where taken from 50-60 men for each dosage group , and the Testosterone rise was consistent across the board. Except for 0,5mg and 2,5mg which both showed an increase of 27% ?? :woot:

Testosterone increased 4.4% for Finasteride, 6.4% for 0.05mg Dutasteride, 16% for 0.1mg Dutasteride, and 27% for 0.5mg and 2.5mg Dutasteride. Although the rise in Testosterone may seem high, the Testosterone levels were almost always within normal range according to Rittmaster.

I'm getting an idea now , maybe the DHT type I inhibition across the body does rise blood testosterone significantly (dutasteride's type I inhibition is not so high as type II's BUT 40-50% of alot is still alot) and thus there is more potential for it to attach to androgen receptors . So in the end you have more Testosterone at the follicle than you would have had DHT type I , had you never taken any drugs. The idea is that the testosterone which comes from various DHT type 1 producing sites in the body (due to dutasteride doing it's work there) can now attach to the hair follicle.
Please disprove this paranoid and frightening thought

 

[Bryan]

I'm getting an idea now , maybe the DHT type I inhibition across the body does rise blood testosterone significantly (dutasteride's type I inhibition is not so high as type II's BUT 40-50% of alot is still alot) and thus there is more potential for it to attach to androgen receptors . So in the end you have more Testosterone at the follicle than you would have had DHT type I , had you never taken any drugs. The idea is that the testosterone which comes from various DHT type 1 producing sites in the body (due to dutasteride doing it's work there) can now attach to the hair follicle.
Please disprove this paranoid and frightening thought

The Gisleskog et al studies of finasteride and dutasteride estimate that the fraction of DHT formed by 5a-reductase type 2 is 83%. Does the remaining 17% that's produced by the type 1 enzyme seem like "a lot" to you? Using dutasteride and reducing that remaining 17% by half or so doesn't seem to be all that spectacular a factor.