SARMS for hairloss

[dallasboy]

This is from a thread on elitefitness.com :

I would have some remarks concerning the anabolic/androgenic effects of SARMS and possible implications for side effects (mainly hairloss). More concretely, I would like to comment on four propionamides including Andarine (S-4) and Ostarine (MK-2866). The internet information is often inaccurate and there are a plenty of myths surrounding this stuff. I would like to note that I am not a chemist, but still, I do hope that my contribution will be interesting.

First of all, let‘s look at S-1 and Andarine (S-4) that have the same structure on the A-ring (with NO2 and F3).
(UNFORTUNATELY, I DON'T KNOW, WHY THE IMAGES DON'T APPEAR ON THIS PAGE, SO YOU MUST CLICK ON THE LINKS.)

S-1:
http://lenule056.ic.cz/S-1.jpg

S-4 (Andarine):

S-1
In studies done in rats, S-1 turned out to be minimally androgenic, but not much anabolic. Even at 1 mg/day (=ca. 5 mg/kg, i.e. a dose that would roughly correspond to 70 mg/day in the average human trainee), S-1 was not able to restore the weight of the levator ani muscle to that of an intact animal, but its effect on the prostate was negligible.

S-4 (Andarine)
In S-4, the anabolic effect was higher, but so was the androgenic effect.

http://lenule056.ic.cz/S-4 CURVE.jpg


The comparison of S-1 and S-4 with anti-androgens and finasteride
When in another study both S-1 and S-4 were compared with testosterone (TP) in castrated and intact rats, some interesting effects were revealed (dosages 0.5 mg/day):

As you can see, the results in castrated rats are similar to the previous study: S-1 was little androgenic and anabolic, S-4 was both more androgenic and anabolic and vastly superior in this regard to testosterone.

However, prostate weight in intact rats treated with S-1 and S-4 decreased, which suggests that these compounds work as competetive agonists of dihydrotestosterone in the prostate. In other words, they block the binding of dihydrotestosterone to androgen receptors, and considering that they are little androgenic, the androgenic action in the prostate decreases.

S-1 was subsequently compared with an anti-androgen (hydroxyflutamide) and finasteride in intact rats. At relatively high doses (5-25 mg/kg), S-1 decreased prostate weight to ca. 50%, i.e. to a similar extent like these compounds. This is really very interesting, because it indicates that the more you take it, the less your sensitive tissues (hair, prostate) are affected by androgenic side effects!

We can suppose that S-4 would be less effective in this regard (I would guess that it would be able to reduce prostate weight to ca. 65% at most, judging from the constant 15% difference between S-1 and S-4 in the graphs), but still, it would be a very, very safe stuff for the user, because even megadoses of S-4 (10 mg/kg, which would correspond to ca. 145 mg/day) don’t restore prostate weight to 100%. (Although it is true that S-4 in this study shows a considerably less androgenic activity than in other studies.)

Would the anti-androgenic effect of propionamide SARMS be reversed at a certain point? It is quite expectable and a study of S-23 (a compound that is structurally more similar to Ostarine) indeed suggests that this would happen.

S-23

Ostarine

S-23
S-23 was investigated in a special study, and this curve of its anabolic/androgenic effect was obtained:

Apparently, S-23 is highly anabolic even at very low doses, and its anabolic/androgenic ratio is very advantageous at low doses as well, but above 0.3 mg/day (=ca. 1.5 mg/kg, i.e. roughly 20-25 mg/day in humans), its androgenicity sharply increases.

The effect of S-23 in intact rats largely confirms, what I said: S-23 decreases prostate weight up to a certain point (0.3 mg/day), but then this trend is reversed, in accordance with the rapid increase of androgenic activities in the graph above. Thus, this stuff has its „sweet point“ with a very benefical effect on the body, yet at higher doses, it becomes quite harsh.

CONCLUSION:
What are possible implications for people taking propionamide SARMS? Well, we must take into consideration that lab tests done in animals do not translate perfectly to humans, but these compounds apparently share some typical characteristics.

S-1 and S-4 have a very favourable profile, as for the risk of hair loss. In fact, they probably work against hair loss and could be used for this purpose in a similar way like finasteride. They seem to be very safe in this regard, and even megadoses of S-4 like 100 mg/day and S-1 like 400 mg/day should be beneficial. (But other side effects at these doses are another story, of course, and especially in S-1 that was not practically investigated in humans.)

As for S-23, I mentioned it, because it is structurally similar to Ostarine. Unfortunately, I couldn’t find any animal studies on Ostarine, so I can only speculate that it shares some characteristics with S-23. S-23 is very effective in low dosages, and its half-life is also quite long (11-12 hours), similarly like in Ostarine.

If it were true, it means that Ostarine would be extraordinarily advantageous when taken in low doses, but after a certain „sweet point“, its side effects could quickly outweigh benefits. Well, this is a pure speculation, but it could give us some insight into the Ostarine’s mode of action. Personally I would be careful with the dosage of Ostarine, because I have been on minoxidil for nearly 16 years and I value my hair more than muscles.

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More:

Update: Ostarine (1 mg/day) decreases prostate size in intact rats, similarly like S-1 (to 64% of its original size) and S-4 (to 79%) at 0.5 mg/day.

The comparison of dihydrotestosterone (black bars) with Ostarine (striped bars):

http://lenule056.ic.cz/OSTARINE - intact prostate.jpg

I can't find the original source of this graph, but in any case, the decrease is about -25%. The dosage 1 mg/day would correspond to ca. 5 mg/kg, i.e. ca. 0.80 mg/kg in humans.

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The theory, and GTX filed a patent on this and was granted it earlier this year, is that SARMS bind to the AR in the prostate and hair follicles and block DHT similar to the way finasteride does. BUT, your body still producs DHT and you get the intended benefits, just they cannot attack the hair follicle (or are diminished in doing so). If your not familiar with SARMS, google them.

 

[WarLord]

LOL This is actually my post. Thanks! Well, in theory, it really works very well. S-1 even showed a somewhat better effect on rats' prostate than a superdose of finasteride. In fact, the more you take it, the less your hair should be affected! This may work only up to a certain point, of course, when the rising androgenicity of a SARM matches DHT. But most of these propionamide SARMs are so little androgenic that they can't restore prostate weight even at very high dosages. The only exception seems to be S-23. The problem is that what works well in rats may not work so well in humans. But the results are very consistent, fortunately.

What is interesting on that patent, however, is the fact that the authors presented SARMs rather as potential DHT blockers, not as competetive agonists. The text is very long and repetetive
http://www.faqs.org/patents/app/20100280107
but you can find the Example 1 "Interaction Between Compound VI and Human 5α-Reductase", where this anti-DHT effect is mentioned. As far as I know, the anti-DHT effect of SARMs is very small, and can hardly be achieved in vivo. The competetive agonist activity is therefore more interesting, and is demonstrated in the example 2 "Pharmacologic Activity and Tissue Selectivity of Compound VI in Rats of Varying Hormonal Status". The compound VI is Andarine (S-4).

 

[dallasboy]

LOL This is actually my post. Thanks! Well, in theory, it really works very well. S-1 even showed a somewhat better effect on rats' prostate than a superdose of finasteride. In fact, the more you take it, the less your hair should be affected! This may work only up to a certain point, of course, when the rising androgenicity of a SARM matches DHT. But most of these propionamide SARMs are so little androgenic that they can't restore prostate weight even at very high dosages. The only exception seems to be S-23. The problem is that what works well in rats may not work so well in humans. But the results are very consistent, fortunately.

What is interesting on that patent, however, is the fact that the authors presented SARMs rather as potential DHT blockers, not as competetive agonists. The text is very long and repetetive
http://www.faqs.org/patents/app/20100280107
but you can find the Example 1 "Interaction Between Compound VI and Human 5α-Reductase", where this anti-DHT effect is mentioned. As far as I know, the anti-DHT effect of SARMs is very small, and can hardly be achieved in vivo. The competetive agonist activity is therefore more interesting, and is demonstrated in the example 2 "Pharmacologic Activity and Tissue Selectivity of Compound VI in Rats of Varying Hormonal Status". The compound VI is Andarine (S-4).

Hey WarLord, didn't mean to not give ya credit ;-). It's all very interesting stuff and thanks for the research!

 

[WarLord]

I should add that in August 2012 I experienced an unprecedented hair regrowth on minoxidil+finasteride+SARMs (ca. 10-15 mg Ostarine/day, 30-40 mg S4/day). For a while, it looked that I could restore my Norwood1 hairline again. However, after I quitted SARMs in late August, the regrowth immediately stopped, and since late October 2012, I was going through an ordeal: My hairloss resumed after long 16 years again. It was not much dramatic, but it was an incessant, continuous loss. I hoped that it was only a temporary "finasteride shed", but it wasn't. I found a laboratory doing tests of blood DHT levels and it turned out that my DHT is low, but still within the normal range. Finasteride was doing basically nothing. In early February 2013 I lost patience and I jumped on dutasteride, which eventually saved me. My DHT is currently almost unmeasurable.

I suspect that the combined use of finasteride and SARMs was beneficial for regrowth, but that it also upregulated androgen receptors. After I quitted SARMs, the rising androgen levels overpowered both finasteride and minoxidil, despite the fact that my DHT must have been much lower than before the start of finasteride use. It is bizarre, but otherwise I couldn't explain the subsequent loss. In any case, I won't use SARMs again. It is an unpredictable stuff.