A brief report on the 'new' dutasteride study!

[Bryan]

About a month and a half ago, Guillermo alerted us all to a supposedly "new" dutasteride study that had just appeared in one of the medical journals. As I pointed out at the time, it wasn't actually anything new, just the formal publication of the same clinical trial for hairloss that Glaxo did a few years ago. The essential data from that trial (haircounts, side-effect percentages, etc.) have already been available for a long time and have been widely discussed on these hairloss sites. However, I just obtained the full 10-page study from the medical library this evening, and I've given it a quick read-through. All the haircount data is exactly the same as what we've known for a long time, but there are a couple of other minor surprises which I wasn't expecting:

1) They also performed both serum and scalp before-and-after testosterone and DHT measurements on the various treatment groups (dutasteride, finasteride, and placebo)!

2) The main efficacy end-point was the haircount data, but they also did expert panel and investigator photographic assessment of not only vertex improvement, but also frontal improvement!

I personally have never been particularly interested in measurements of scalp DHT, for reasons which I've already explained until I'm blue in the face. However, I know that many of the rest of you are, so I'll quote a few passages from the text of the study on what their results were, along with their own brief discussion of another earlier study which got very different results. Also, this theory about losing frontal hair on dutasteride has been all the rage lately, so I'll quote what they said about the photographic assessment of the frontal part of the scalp while on dutasteride and finasteride. Here are the two sections, one after another:

Materials And Methods. Scalp testosterone and DHT concentrations were determined in 4-mm biopsy specimens taken at baseline and again at 24 weeks. The biopsy specimens were taken anterolateral to the leading edge of the vertex bald spot, adjacent to the target area for hair counts. Scalp testosterone and DHT were measured after tissue homogenization and ether extraction, using the same assay as for serum measurements. Results. [...] Scalp DHT concentrations in the dutasteride groups were also significantly suppressed compared with placebo in a dose-related manner. As with serum DHT, the 0.1-mg dutasteride and finasteride groups showed a comparable degree of scalp DHT suppression (32% and 41%, respectively). Scalp DHT decreased by 51% with 0.5-mg dutasteride and by 79% with 2.5-mg dutasteride. Scalp testosterone levels significantly increased in all active treatment groups compared with placebo, increasing by 23%, 39%, 99%, and 222% with 0.5-, 0.1-, 0.5 and 2.5-mg dutasteride, respectively, and 23% with finasteride.

Materials And Methods. [...] For expert panel assessment of global changes in the amount of hair, photographs were taken of both the vertex and frontal scalp. A panel of experts (Drs Olsen, Savin and Whiting), blinded as to treatment, was shown pairs of photographs from baseline and either 12 or 24 weeks of treatment from each view. The panel graded the changes in hair growth on a 7-point rating scale: greatly, moderately, or slightly decreased; no change; slightly, moderately, or greatly increased; ratings were then converted to numbers (-3 to +3) for statistical analysis. [...] Investigator and subject assessments were done at baseline and at 12 and 24 weeks. For the investigator assessments, baseline photographs were provided for comparative purposes and the investigators used the same 7-point rating scale al already described for the expert photographic panel. The subjects were asked to rate changes in the size of the vertex spot, hair loss on top of the scalp, bitemporal recession, the amount of hair shedding, hair quality, and overall satisfaction with hair growth on a 3-point scale (improved, no change, or worse). Results. [...] In the frontal region, the dutasteride 0.1, 0.5, and 2.5 mg groups improved significantly more than placebo at both 12 and 24 weeks. Finasteride was not significantly different from placebo at 12 weeks (P = .69) but was at 24 weeks (P < .001). At 12 weeks, the improvement in the 0.5-mg dutasteride group (0.28 +/- 0.40) and in the 2.5-mg dutasteride group (0.37 +/- 0.46) was significantly greater than the finasteride group (0.09 +/- 0.39, P = .009 and P < .001, respectively). At 24 weeks, the improvement in the 2.5-mg dutasteride group (0.85 +/- 0.79) was also significantly greater than the finasteride group (0.51 +/- 0.66, P = .002). The proportions of patients judged to have improved hair growth (slightly to greatly increased) at 24 weeks in the frontal photographs were 12%, 22%, 33%, 48%, and 61% for placebo, 0.05, 0.1, 0.5 and 2.5 mg dutasteride, respectively, and 45% for finasteride. The proportion of patients with moderate or greater increases was higher with dutasteride 0.5 and 2.5 mg than with finasteride for both vertex and frontal photographs. Investigators' Global Assessment. [...] At the frontal scalp....the 2.5-mg dutasteride group also showed a significant increase compared with finasteride (P < .001) at 12 weeks. At 24 weeks, dutasteride 0.1, 0.5, and 2.5 mg and finasteride groups showed significantly more improvement than the placebo group. The 2.5-mg dutasteride group (1.38 +/- 0.93) was also significantly more improved than finasteride (0.83 +/- 0.95, P < .001).

So there you have it: despite some pretty wild conspiracy theories floating around here that the researchers noticed frontal thinning during the Glaxo trial and that that's at least one of the reasons why they stopped further male pattern baldness development for dutasteride, that claim isn't supported by this study. Both the expert panel and the investigators reported significantly improved FRONTAL hair in the dutasteride groups than in the finasteride group.

Bryan

 

[SkylineGTR]

excellent.

 

[techprof]

Bryan,
thanks very much. Hopefully this will stop the whining about frontal loss with dutasteride.

 

[bubka]

wow, now that is some awesome data...

i always speculated that dutasteride would be best at .1mg for male pattern baldness as it compares to the finasteride male pattern baldness ratio; however, it seems that a higher dutasteride dosage is beneficial in reducing scalp dht, though the major increase in T is concerning... i have to read into this some more

thanks Byran, what was the source?

though with it so promising, and their date showed this over finasteride, why did they not let it go further??? because of the dramatically higher dosage over the BPH dosage which is the opposite of finasteride? no that I don't think that is a really decent reading, but i don't know?

 

[plusryan]

Thanks a lot Bryan, this gives me more hope for my hairline and my overall confidence!

 

[Old Baldy]

Way to go Bryan!! Thanks for the info.!

 

[Bryan]

thanks Byran, what was the source?

It's unusual for me not to provide a source like that. I guess I was in a hurry to get all that information out!

"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." J Am Acad Dermatol 2006;55: 1024-23.

though with it so promising, and their date showed this over finasteride, why did they not let it go further??? because of the dramatically higher dosage over the BPH dosage which is the opposite of finasteride? no that I don't think that is a really decent reading, but i don't know?

I think it's mainly simple economics: they didn't think they'd make enough money to be worth paying the huge additional amount for FDA approval for the new indication (male pattern baldness).

Bryan

 

[Guest]

Bryan,

few questions if you don't mind:

1) Do you think that taking 2.5 mg of dutasteride every day for a year is "safe"?

2) Do you think that the extra gains from taking 2.5 mg of dutasteride over 0.5 mg of dutasteride could be maintained if one switched back to 0.5 mg after regrowth was complete?

3) How can we explain the people on here who claim that dutasteride gave them terrible frontal sheds that never grew back? Are they simply mistaken or do you think some of them had some kind of weird reaction to the drug? I don't understand how the drug could cause irreversible frontal sheds. I personally think that people just don't give the drug enough time to work. They see a nasty shed and stop the drug, and in some cases the hair never grows back. What do you think? I had a nasty shed after about 5 weeks on the drug but I'm approaching 5 months on avodart now and it seems to have all come back along with a bit extra.

Thanks.

 

[Bryan]

Bryan,

few questions if you don't mind:

1) Do you think that taking 2.5 mg of dutasteride every day for a year is "safe"?

Probably, but the thought of going much longer than that makes me queezy.

2) Do you think that the extra gains from taking 2.5 mg of dutasteride over 0.5 mg of dutasteride could be maintained if one switched back to 0.5 mg after regrowth was complete?

Dunno for sure, but I tend to doubt it.

3) How can we explain the people on here who claim that dutasteride gave them terrible frontal sheds that never grew back? Are they simply mistaken or do you think some of them had some kind of weird reaction to the drug?

Dunno. That's the "$64,000 Question" (that's a reference from long before your time! ). There's even a fellow who posts on hairsite who made such a claim, and I trust his judgement. He's a very technical type who works for a drug company. I just don't know what to make of those claims.

I don't understand how the drug could cause irreversible frontal sheds.

Me neither.

Bryan

 

[Bertie]

A few quibbles about the study.

In the "Discussion" section the authors write:

The greater efficacy of 2.5-mg dutasteride[compared with 5mg finasteride] shown herein supports the dual role of type 1 and type 2 5α-reductase in the pathogenesis of MPHL.

Well, no, not really, because the improved performance of dutasteride could also be due to its superior performance at inhibiting the type 2 enzyme. If I remember right from other data posted on this site, Proscar gives 90% type 2 inhibition while Avodart gives 98.5%, or something like that, and it is certainly possible that that alone accounts for the difference in performance as a male pattern baldness treatment, not anything to do with type 1 5AR.

The results of this study also highlight the importance of scalp DHT in the pathogenesis of MPHL.

Again, not really. The study does establish that scalp DHT is reduced more by dutasteride than finasteride, but does not establish that scalp DHT is actually that relevant -- the authors do mention in passing that 5AR is present in the hair follicle without considering that that 5AR might be what really matters.

(Has anyone attempted to measure DHT reduction or 5AR inhibition within the follicle on various drugs, as opposed to the more blunt "scalp DHT" measurments?)

 

[Guest]

(Has anyone attempted to measure DHT reduction or 5AR inhibition within the follicle on various drugs, as opposed to the more blunt "scalp DHT" measurments?)

that's where the 98.5% number comes from, I believe, Bertie.

98.5% inhibition of 5ar type II in the follicles with 0.5 mg dutasteride every day.

50% inhibition of 5ar type I in the follicles with 0.5 mg every day

Just an example

Bryan can correct me if I'm wrong.

 

[Timi]

dutasteride

But the Sex drive is with dutasteride 0,5mg Daily Down
2,5 mg dutasteride was light better as 5mg Proscar (Study)
but 5mg Proscar to 1mg Proscar no better Effect
Result
than is 1mg Proscar nearly so Good as 2,5mg dutasteride

and who swallows 2,5mg dutasteride????

Timi

 

[Bryan]

A few quibbles about the study.

In the "Discussion" section the authors write:

The greater efficacy of 2.5-mg dutasteride[compared with 5mg finasteride] shown herein supports the dual role of type 1 and type 2 5α-reductase in the pathogenesis of MPHL.

Well, no, not really, because the improved performance of dutasteride could also be due to its superior performance at inhibiting the type 2 enzyme. If I remember right from other data posted on this site, Proscar gives 90% type 2 inhibition while Avodart gives 98.5%, or something like that, and it is certainly possible that that alone accounts for the difference in performance as a male pattern baldness treatment, not anything to do with type 1 5AR.

[quote:7fab6]The results of this study also highlight the importance of scalp DHT in the pathogenesis of MPHL.

Again, not really. The study does establish that scalp DHT is reduced more by dutasteride than finasteride, but does not establish that scalp DHT is actually that relevant...[/quote:7fab6]

I had exactly the same quibbles with the study! I thought it was rather superficial of them not to at least acknowledge the issues you mentioned above.

There's no doubt in my mind that both inhibitions (type 1 and type 2) from dutasteride contribute to its greater success over finasteride, but the really interesting question is, what is the relative degree of importance of the two? Is it about 50/50, or is it more 60/40 or 40/60? Or is it 90/10 or 10/90? :lol:

(Has anyone attempted to measure DHT reduction or 5AR inhibition within the follicle on various drugs, as opposed to the more blunt "scalp DHT" measurments?)

Not to my knowledge.

BTW, I like your use of the word "blunt" in that context! :wink:

Bryan

 

[Bryan]

(Has anyone attempted to measure DHT reduction or 5AR inhibition within the follicle on various drugs, as opposed to the more blunt "scalp DHT" measurments?)

that's where the 98.5% number comes from, I believe, Bertie.

98.5% inhibition of 5ar type II in the follicles with 0.5 mg dutasteride every day.

50% inhibition of 5ar type I in the follicles with 0.5 mg every day

Just an example

Bryan can correct me if I'm wrong.

I think what he means is, has anybody made DIRECT measurements of DHT within hair follicles, without merely assuming that the relative inhibitions of the two enzymes within hair follicle cells are about the same as they were measured to be (across the whole body) in the Gisleskog et al studies?

As far as I know, microdissecting hair follicles from scalp biopsies and subjecting them to such tricky and difficult testing hasn't been done.

Bryan

 

[Timi]

dutasteride

Hello Bryan

what ist the best dr. Procter Produkt for the Fronthairs?
i have the Shampoo (Daily)
and Prox-N but is empty (take it 2Month)

dutasteride
Daily 0,25mg but my Sex Drive is Down
this is for long time bad i have Hairs but No Sex

under Proscar No Problems

Timi

 

[chowmein]

Re: dutasteride

dutasteride
Daily 0,25mg but my Sex Drive is Down
Timi

Timi, how are you taking 0.25mg dutasteride ? How do you split the dutasteride gel cap?

 

[Fat-Elvis]

Re: dutasteride

dutasteride
Daily 0,25mg but my Sex Drive is Down
Timi

Timi, how are you taking 0.25mg dutasteride ? How do you split the dutasteride gel cap?

.5 every other day, maybe?

 

[CCS]

significant just means statistically significant, meaning there was indeed a difference on average.

I don't think anyone ever doubted that dutasteride was worse on the front than placebo. The good part about the study is it showed frontal hair improving with increased dose, and 0.5mg/day out performing proscar in front.

The only reason I'm skeptical still is those hormone levels are NOT the same as the ones in the famous phaseII study reported on hairsite.

And my front has definitely gone way down hill. I don't see how it can be a minoxidil shed if I was never that consistent with minoxidil.

 

[Timi]

dutasteride

chowmein

Yes i split the dutasteride Gel Cap
i put it in a emty Cap 50%old Cap -and 50% in a emty Cap

Timi

 

[SkylineGTR]

thats odd. why not just take one every other day.