Here's the MK386 study with stumptailed macaques

[Bryan]

This abstract was published in J Invest Dermatol 1995; 104:658.

"Effects of a 1 Year Treatment With Oral MK386, an Inhibitor of Type 1 5a-reductase, in the Stumptailed Macaque (Macaca Arctoides)". Linda Rhodes, Raymond Primka, Charles Berman, Gloria Gato, Joanne Audette-Arruda, Bill Pikounis, Bozena Matuszewska and James Harper, Merck Research Laboratories, Rahway, N.J. and West Point, PA., Brown University, Providence, R.I.

Human type 1 5a-reductase (5a-R) is the enzyme that converts testosterone to dihydrotestosterone (DHT) in non-genital skin and sebaceous glands. A specific inhibitor of type 1 5a-R, MK386 (4,7b-dimethyl-4-azacholestan-3-one), was used to test the effect of such a compound on hair growth in the stumptail macaque, a commonly used model of human androgentic alopecia. Animals were matched by weight, age and sex and divided into two groups; MK386 treated (oral 1 mg/kg/day; n=6 females, 7 males) or vehicle treated (n=5 females, 6 males). Hair shaved from a pre-marked 1 sq in. area was weighed and blood was collected once/month. Samples from 19 months were collected; 7 months baseline, 12 months on treatment. DHT was measured in serum of selected animals. Preliminary data from males showed MK386 treatment caused a 30-50% decrease in serum DHT. Final analysis of hair weights from all animals showed mean weights were similar in both groups (p>0.25). Large monthly variations in hair weights were observed (p<0.001), emphasizing the need for long term studies in this model. These results contrast with those from a previous study in stumptailed macaques using an inhibitor of type 2 5a-R (finasteride, 1 mg/kg/day, orally) which caused an increase in hair weights during 6 months of treatment. (1)

(1) Rhodes, et al., J. Clin. Endocrinol. Met. 79: 991-996, 1994.

 

[michael barry]

Bryan,

Thank you very much for posting this. I suppose this should end the debate on type 1 alpha 5 DHT, but I know that there is some contrarian jerk-off out there who will still insist that its a cause of male pattern baldness, just to debate for the fun of it.

Great stuff Byran.

 

[CCS]

One thing I find interesting is that in the phaseII FDA dutasteride hair loss trials, 2.5mg/day regrew about 25% more hair on average than 0.5 mg/day, even though 0.5mg/day inhibits 98.5% (if I remember correctly) of DHT production from 5ar type 2. I have to wonder if hairs are so sensitive that the extra 1% of DHT made in the follicle made that much of a difference, or if the DHT from type 1, which dropped 85% instead of just 50%, could have some part in this.

I believe that DHT produced inside the follicle does the majority of the damage, perhaps 90%, but that DHTf from the nearby sebacious glands does do some small damage, whose fluctuation is more noticeable when most follicle produced DHT is gone. However, due to brain issues, I do not think it is worth going after the 5ar1 for the small extra benifit, since there still are other androgens doing damage. I believe topical 5ar1+2 blockers and androgen receptor blockers are the next line of defense after 0.5mg/day. So are SODs.

 

[Aplunk1]

Bryan, is this one study enough to rule out, for good, the possibility of 5AR-I as a possible treatment for Androgenetic Alopecia?

 

[Bryan]

Bryan, is this one study enough to rule out, for good, the possibility of 5AR-I as a possible treatment for Androgenetic Alopecia?

Oh, heavens no. I think that inhibiting 5AR-I definitely IS a treatment for Androgenetic Alopecia, it's just not a very good one when used alone. The fact that the Glaxo trial with dutasteride showed that the 2.5 mg/day dose produced about an 11.4% better haircount improvement (compared to placebo) than the 0.5 mg/day dose seems to prove that inhibiting the type 1 enzyme is helpful, at least when you've already suppressed type 2 sufficiently. At either one of those two doses, the type 2 enzyme is inhibited almost completely; the only difference is the degree of inhibition of the type 1 enzyme.

I've always been careful to mention that I feel that indigenously-produced follicular DHT is responsible for the great majority of male pattern balding, but not ALL of it. Dutasteride's slightly better effectiveness at larger doses is apparently due either to its greater suppression of total serum DHT, or perhaps to the additional suppression of the type 1 enzyme found in certain other areas of the hair follicle, or both of those.

BTW, I should also mention here that a well-known poster on these hairloss sites told me a while back that he talked to a Merck doctor/scientist on the phone, and was told that Merck also did a trial with HUMANS with a specific type-1 inhibitor (very likely MK386), and got no noticeable results. The Merck guy admitted that they were "surprised" at the lack of results for balding. Funny how much we've learned in just the last few years! :wink:

Bryan

 

[Felk]

It always amuses me how these things are worded

Ie "The women were shaved, and hair count weights were obtained"

The image of a bunch of mad scientists applying creams and shaving monkeys and hirsute women... it's almost like something out of the Far Side :lol:

 

[Guest]

I believe topical 5ar1+2 blockers and androgen receptor blockers are the next line of defense after 0.5mg/day. So are SODs.

What topical 5ar1+2 blockers are there besides spironolactone? I assume spironolactone is one of them? I keep hearing about RU this and RU that but is it even available and affordable yet?

 

[Felk]

I believe topical 5ar1+2 blockers and androgen receptor blockers are the next line of defense after 0.5mg/day. So are SODs.

What topical 5ar1+2 blockers are there besides spironolactone? I assume spironolactone is one of them? I keep hearing about RU this and RU that but is it even available and affordable yet?

You import the raw chemical powder from China, and mix your own. If you use 2ml a day, it's $100 a month, $50 if you use 1ml. I hope this helps... :shock:

 

[CCS]

Felk, that would depend on the concentration.

Jayman, spironolactone is not a 5ar blocker. it is just an AR blocker. 5 18 carbon fatty acids might be 5ar blockers, but I suspect they just reduce the number of 5ar enzymes, which would appear the same to scientists unless they could isolate 5ar.

As for AR blockers, there is spironolactone, fluridil, RU, and oleic acid. Other 18 carbon fatty acids also work, but again, I think the fatty acids reduce the number of androgen receptors, rather than block them.

I've not seen any studies on this. I just strongly suspect it.

 

[Felk]

Yeah, that's true, but I'm just going off the recipe suggested to me by Faith Eagle's representative (the one stax used too, with great success)

 

[CCS]

It always amuses me how these things are worded

Ie "The women were shaved, and hair count weights were obtained"

The image of a bunch of mad scientists applying creams and shaving monkeys and hirsute women... it's almost like something out of the Far Side :lol:

I want to do a study to see if spironolactone reduces female pubic hair. I'll be one of the scientists who does the shaving. But I'll screen the study participants so only the hot ones join.