SARMs S4 and PCT?

[MesomorphosisGuy]

At high bodybuilding doses, it likely contributes to HPTA shut down. In small doses, not.

Solo

S-4 didn't influence the levels of FSH and LH even at 0,75 mg/day, which was the maximum anabolic dose in castrated rats.

S-1behaved differently, and markedly reduced both FSH and LH at effective doses of 0,5-0,75 mg/day.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040238/?tool=pubmed.

Naturally, if you use such crazy useless dosages like 150 mg/day, the suppression of endogenous hormones will occur.

 

[carter]

I read somewhere that the UG S4 is tainted with methanol which is toxic to humans and might be causing the yellow vision/bad night vision.

I've ready this too, and believe (hope) it to be unfounded.. The studies which have been done so far on S4 for geriatric use, which are limited, do indicate slight vision occurences, change of color, problems with night vision, etc..certainly these university studies aren't using UG S4................

 

[buddy1]

This stuff sounds promising. I think I'll wait on using it until we know more about the long term effects. The vision thing is pretty scary, even if it goes away when discontinuing usage.

 

[Conciliator]

S-4 didn't influence the levels of FSH and LH even at 0,75 mg/day, which was the maximum anabolic dose in castrated rats.

That's not what the paper said. To quote them, "The activities of S-4 on LH and FSH were similar to those produced by TP. S-1 and S-4 partially suppressed LH production at dose rates of 0.5 mg/day or higher."

An absolute dose of 0.5 mg/day is equivalent to 1.9 mg/kg/day in the rats studied. When corrected for body surface area and converted to dosing for humans, you get 0.31 mg/kg (1.9 * 0.162). As a theoretical extrapolation, for a 100 kg (220 lb) man, a dose of only 31 mg/day is where you'd start to see "partially suppressed LH production."

 

[Conciliator]

The studies which have been done so far on S4 for geriatric use, which are limited, do indicate slight vision occurences, change of color, problems with night vision, etc.

I believe that only one study (singular) has been done on S4 (ostarine) in the elderly. And from what I've read. there was no mention of any vision abnormalities. For example, http://phx.corporate-ir.net/phoenix.zhtml?c=148196&p=irol-newsArticle&ID=940363&highlight= the press release. If you have any evidence to support your contention that they found "slight vision occurrences, change of color, problems with night vision, etc" please post it.

 

[Millard]

That's not what the paper said. To quote them, "The activities of S-4 on LH and FSH were similar to those produced by TP. S-1 and S-4 partially suppressed LH production at dose rates of 0.5 mg/day or higher."

What does this mean for libido?

 

[Michael Scally MD]

SARMs

The future use of SARMs is of interest for a number of reasons. First, anyone stating they have access to SARMs is likely lying. There is a considerable amount of fraudulent AAS on the street and this is undoubtedly another source to scam people out of their money. Second, the literature regarding the HPTA is extremely limited, possibly due to the fact that the companies do not want this information public (for obvious reasons - FDA approval).

In SARM publications, they do state that LH is suppressed. Selectivity with regard to gonadotropin suppression represents a significant barrier to the clinical use of SARMs. [Gao W, Dalton JT. Ockham's Razor and Selective Androgen Receptor Modulators (SARMs): Are We Overlooking the Role of 5{alpha}-Reductase? Mol Interv 2007;7(1):10-3.] It will be interesting to view the results for the serum testosterone.

See: Ockham?s Razor and Selective Androgen Receptor Modulators (SARMs): Are We Overlooking the Role of 5?-Reductase? ? MI or Ockham's Razor and Selective Androgen Receptor Modulators (SARMs): Are We Overlooking the Role of 5?-Reductase?

Do not expect these authors to be more forthcoming about these compounds. The reason - Dalton is now an employee of GTXI. GTXI, along with LGND (Ligand) are the companies pursuing SARMs for FDA approval.

The coauthor of the above article is an employee of GTXI! The company does not state the problem of AIH. Instead, this will be a blockbuster drug. In my opinion, the company has a very high hurdle for FDA approval. Their clinical endpoint is a soft target and probably not acceptable.

The chief executive officer of GTx Inc said his company's experimental Ostarine medicine to build muscle mass in cancer patients and in the elderly has enormous sales potential and is several years ahead of rival treatments in clinical trials.

Mitchell Steiner said Ostarine has greater sales potential than GTx' best-known experimental drug, called toremifene, which is now in late-stage studies to prevent prostate cancer and to prevent side effects caused by standard treatments for prostate cancer.

"I do believe the market ultimately is larger; it's a huge market," Steiner said, when asked if Ostarine being developed in partnership with Merck & Co had bigger sales potential than the company's flagship toremifene product.

http://www.pharmaceutical-technology.com/news/news41419.html

Finally, if these compounds do not cause AIH, they will potentially show the existence of AAS dependency (maybe called SARM dependency). However, as expected, SARMs from the available public literature cause AIH.

 

[Michael Scally MD]

James T. Dalton

James T. Dalton, Ph.D., Vice President, Preclinical Research and Development.

GTx Management Team

 

[Michael Scally MD]

Following up on my prior posts, a few things of possible interest. The two companies pursuing SARMs are GTXI and Ligand. These companies have serious money behind the R&D. Backers include Merck, Johnson & Johnson, and TAP.

Links:
GTXI: GTx. Hormone pathways to treat cancer, bone loss, muscle wasting
LGND: Ligand Home

Thanks Conciliator for pointing out the importance of data. The doses of these drugs can not be translated one to another. But as Conciliator states, taking an approximate between S-1 and S-4 is clear for using orders of magnitude too high a dose. This is darn good judgment.

Side effects are a dangerous omen of things going terribly wrong in a nonapproved drug. If the skin is turning yellow, this is probably one of the most dangerous signs of all - liver toxicity demonstrating a rise in bilirubin. This can prove to be fatal.

There are theoretical and academic exercises to explore if these drugs do not induce hypogonadism. However, until shown conclusively to be the case, it is smart to assume that after stopping androgens (steroidal and nonsteroidal), androgen induced hypogonadism ensues. For this reason, one should get blood work to check out the HPTA status.

 

[Michael Scally MD]

Otc sarm

I mention that the chance of obtaining an actual SARM is small, most likely receiving bogus product. There are multiple instances, though, where the real McCoy is present. I see this in my own practice. In fact, I was responsible for the nationwide seizure of Triax, a purported weigh loss supplement. This was a result of my reporting to MedWatch and the immediate follow-up with a visit by FDA officials. Thanks to Millard for sending me the link (full text) for the following article (see below). Following is the abstract:

Mario T, Hans G, Matthias K, Wilhelm S. Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product. Drug Testing and Analysis 2009;1(8):387-92.

Non-steroidal and tissue-selective anabolic agents such as selective androgen receptor modulators (SARMs) represent a promising class of therapeutics for the treatment of various diseases such as sarcopenia or cancer cachexia. Advanced compounds of SARMs are based on an arylpropionamide-derived structure and leading drug candidates have successfully completed phase-II-clinical trials. Although none of these therapeutics have been approved, their performance-enhancing qualities and the black-market availability of these products makes them a viable target for misuse in the athletic community. In 2008, SARMs were added to the Prohibited List established by the World Anti-Doping Agency (WADA). That SARMs are the subject of misuse even without clinical approval was proved for the first time by the detection of the drug candidate Andarine (also referred to as S-4, S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide), advertised, sold and supplied via the Internet. The oily liquids, declared as green tea extracts and face moisturizer, were assayed using state-of-the-art analytical procedures and S-4 was found at concentrations of approximately 150 mg/mL. The authenticity of the product was demonstrated in comparison to reference material by liquid chromatography, high resolution/high accuracy (tandem) mass spectrometry using positive and negative electrospray ionization, and comparison to reference material. Moreover, an impurity resulting from poor product purification was detected, accounting for approximately 10% of S-4. This consisted of 2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-3-(4-nitro-3-trifluoromethyl-phenylamino)-propionamide.The ease of purchasing non-approved drug candidates that could potentially increase athletic performance demonstrates the need to operate proactively in the continued fight against doping. The early inclusion of emerging drugs into routine sports drug testing procedures is a key element of preventive doping research, limiting the options for cheating athletes who aim to undermine the doping control system. Copyright 2009 John Wiley & Sons, Ltd.

Wiley InterScience :: Session Cookies

 

[MesomorphosisGuy]

That's not what the paper said. To quote them, "The activities of S-4 on LH and FSH were similar to those produced by TP. S-1 and S-4 partially suppressed LH production at dose rates of 0.5 mg/day or higher."

An absolute dose of 0.5 mg/day is equivalent to 1.9 mg/kg/day in the rats studied. When corrected for body surface area and converted to dosing for humans, you get 0.31 mg/kg (1.9 * 0.162). As a theoretical extrapolation, for a 100 kg (220 lb) man, a dose of only 31 mg/day is where you'd start to see "partially suppressed LH production."

S4 still looks less suppressive than testosterone in this regard.

The data must be taken with a grain of salt.

 

[carter]

I need to get me some S4!

 

[StabMe]

Re: Otc sarm

What would be the lowest dose (mg/kg) you guys would recommend, which would still exert an anabolic or at least anticatabolic effect? I plan to use it during PCT after a long cycle and hope it will help me save some muscle, but i don't want those nasty side effects and want to try the lowest effective dose.

 

[Conciliator]

Re: Otc sarm

What would be the lowest dose (mg/kg) you guys would recommend, which would still exert an anabolic or at least anticatabolic effect? I plan to use it during PCT after a long cycle and hope it will help me save some muscle, but i don't want those nasty side effects and want to try the lowest effective dose.

I'd say 10-30 mg/day.

 

[StabMe]

Re: Otc sarm

I'd say 10-30 mg/day.

Think i am gonna try it this PCT. Thanks.

 

[rich818dubs]

ostarine is the way to go much better than s-4 in my opinion. Love the stuff if anyone needs a good source pm me.

 

[porky little keg]

I think that the yellow vision and impaired night vision that people are reporting are side effects of acute overdose of S-4. Chavo, who's selling it over on Pro Muscle, was recommending a dose of 1-3 mg/kg/day "based on current clinical trials," so that's what guys have started using it at. I knew he was full of shit, so I pressed him on what those clinical trials were. He had nothing to say, because they don't exist. The only clinical trials on S-4 are the ones that GTx is doing for Ostarine (their brand name for S-4). But their clinical trials used up to 3mg TOTAL per day, not per kg of bodyweight per day. That's a difference of a couple orders of magnitude. The dosing for this chemical has been WAY too high, because one of the primary people selling it does not understand the research.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2040238 on S-4 in rats found that anabolism in muscle was maxed out at around 0.75 mg or 2.82 mg/kg per day (see results in the levator ani http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2040238&rendertype=figure&id=F5). When corrected for body surface area and converted to dosing for humans, the dose that maxes out the anabolic response would be around 0.46 mg/kg. In a 200 lb male, that works out to about 40 mg/day. That may sound low, but it's still 13 times higher than the highest dose they used in the clinical trials. You sure as hell don't need hundreds of mgs per day.

From my own clinical trials...... at a svelte ~290# I was seeing great results with .5ml a day on non-workout days, and an extra .5 before workouts for a total of 1ml a day at most. Any more than that didn't really do anything more.

Some yellow tint when there was an extreme contrast of light to dark, such as driving at night and having an oncoming car with the headlights on..... it was actually kind of nice to have those dimmed. Got a little stronger, a little less soreness, no aggression, but a lot of increased stamina and endurance.

Never needed PCT as it doesn't suppress.

 

[toothache]

An old thread but a good one!

Excellent info, here!