From EF:
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:
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S-4 (Andarine):
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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.
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S-4 (Andarine)
In S-4, the anabolic effect was higher, but so was the androgenic effect.
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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):
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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!
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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.)
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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
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Ostarine
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S-23
S-23 was investigated in a special study, and this curve of its anabolic/androgenic effect was obtained:
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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.
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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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