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Androgen receptor down-regulation and its effects on muscle growth. Short vs Long Cycles.

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Taeian clark

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Androgen receptor down-regulation and its effects on muscle growth. Short vs Long Cycles.

Short cycles, supplements to improve androgen receptor content, why androgen receptor content matters for muscle growth, why gains stop by week 6.


Androgen receptor down-regulation due to anabolic steroid use has been touted as a myth for a very long time now. A myth due to only looking at the studies that show the initial usage of anabolic steroids and not further into the steroid cycle. These studies that showed anabolic steroids caused an upregulation of the androgen receptor during the initial weeks of use. But, what about after the first few weeks of anabolic use. What about week 4, week 5, week 6 etc. So let's take a look at what happens past the initial weeks of anabolic steroid use.

First cycle newbie gains producing immense amounts of muscle mass without trying?
Many wonder why their first anabolic steroid cycle ends up resulting in astonishing gains in muscle growth and strength, even when they have poor training and dietary habits. Everyone calls it the magic first cycle. Where you can train poorly, eat poorly and still see astonishing results. Yet no other cycle after that first cycle comes even close to comparison in results. But this effect isn't only seen with the first cycle of anabolic steroid use. It's also seen when users have a long lay off as well from anabolic steroid use.
So here is the real picture on how anabolic steroids affect the androgen receptor as time goes on and also why its effects on the androgen receptor are more important than the androgen serum levels as well.

Supporting Data 1;
Below here is a study that actually tested the androgen receptor expression from month 1 to month 6. As the study shows androgen receptor expression was over double during the first month of testosterone use and had basically returned to baseline come month 6.
"TE administration significantly increased skeletal muscle AR protein expression at 1 mo (P < 0.05), but AR returned to baseline levels at 6 mo. Figure 2 shows a representative autoradiogram of a Western blot for skeletal muscle AR from a subject receiving testosterone and a graph of the densitometry data from the treatment group. There was no correlation between the serum testosterone concentration at 1 mo and the change of AR expression from baseline to 1 mo for individuals. "
"The return of AR expression to pretreatment values after 6 mo of continuous androgen administration indicates a steady-state adaptation to the treatment paradigm."
https://physiology.org/doi/full/10.1152/ajpendo.00362.2001
https://academic.oup.com/jcem/article/88/1/358/2846079

Supporting Data 2;
Another snippet here from the study shows us an increased protein synthesis during the initial month again of testosterone use that returns to baseline when retested again at the 6-month mark. However, the benefit of reduced protein break-down is still seen even when androgen receptor content returns to baseline. A minor benefit at best in comparison to the increased AR content on hypertrophy and strength.

"The studies were performed at the General Clinical Research Center at University of Texas Medical Branch. Subjects received stable isotope infusions to determine skeletal muscle protein metabolism at baseline and after 6 months of treatment. "
"Exogenous amino acids increased protein synthesis in both placebo and T groups, but to a lessor degree after 6 months of T treatment."
https://physiology.org/doi/full/10.1152/ajpendo.00362.2001
https://academic.oup.com/jcem/article/88/1/358/2846079

Supporting Data 3;
And here we have some real-world applicable data with a study on the anabolic steroid oxandrolone, where the men had taken the drug for 12 weeks in total. But, the researchers had noted that the men had seen 90 percent of the strength and size gains during the first 6 weeks, and the rest of the 6 weeks only netting a 10 percent benefit in strength and size.
Now even if these were not bodybuilders on a typical bodybuilding diet, this study shows us how powerful anabolic steroids can be, and well magical in its effects on strength and size in normal people within 6 weeks. And yet, only to give disappointing results in the following 6 weeks netting a mere 10 percent more effects in size and strength for double the time on an anabolic steroid cycle. Why would you want to waste 6 weeks of your hard work and time for 10 percent extra results in strength and size when you could come off for a short period to then see those amazing benefits again.

"These changes were >90% of the gains in total and appendicular LBM (3.0 +/- 1.5 kg and 1.3 +/- 0.9 kg, respectively) after 12 weeks. Total thigh and hamstring muscle volume increased by 111 +/- 29 mm(3) (p =.001) and 75 +/- 18 mm(3) (p =.001), respectively, after 12 weeks. Maximal strength increased for the leg press 6.3 +/- 5.6% (p =.003), leg curl 6.7 +/- 8.6% (p =.01), chest press 6.9 +/- 6.5% (p =.001), and latissimus pull-down 4.8 +/- 6.3% (p =.009) with oxandrolone after 6 weeks; these increases were different than those with placebo (p <.001) and were 93%, 96%, 74%, and 94% of the respective gains at week 12. There were no improvements in functional measures. Treatment with a potent anabolic androgen may produce significant increases in muscle mass and strength after only 6 weeks in healthy older men. However, such treatment did not improve leg muscle power or walking speed."
https://www.ncbi.nlm.nih.gov/pubmed/16424293

Supporting Data 4;
Here we have a study that was done on a long ester steroid, testosterone enanthate. Which showed that the peak increase in strength and size was seen by week 3. The increases in strength and size were still seen past week 3 of course, but it had already started to level off by just week 3 alone. Which goes against the popular myth that long ester steroids take 4 plus weeks alone just to kick. Which clearly isn't true just by looking at the graph alone in the study.
https://journals.lww.com/nsca-jscr/...ect_of_Short_Term_Use_of_Testosterone.11.aspx

Why does androgen receptor content matter more than the dose of an anabolic you take?
Lastly, we have why does having optimal androgen receptor expression matter? Well, here we have a study showing us that our androgen levels do not matter in the long run for muscle growth but the actual androgen receptor content itself. Men with better androgen receptor content see immensely more muscle growth compared to men with equal androgen serum levels. So a naturally gifted person with higher androgen receptor content will respond much better to resistance training with higher increases in strength and size than someone with lower androgen receptor content regardless of the androgen serum levels.
This study here shows us what the prior studies have above discussed. That upregulating your androgen receptors is the main factor in your muscle and strength gains. 90 percent of your muscle and strength gains to be exact.

"Unlike intramuscular free testosterone, dihydrotestosterone, or 5α-reductase, there was a linear relationship between androgen receptor content and change in LBM (P < 0.01), type 1 CSA (P < 0.05), and type 2 CSA (P < 0.01) both pre- and post-intervention. These results indicate that intramuscular androgen receptor content, but neither circulating nor intramuscular hormones (or the enzymes regulating their intramuscular production), influence skeletal muscle hypertrophy following RET in previously trained young men."
https://www.frontiersin.org/articles/10.3389/fphys.2018.01373/full

Continued...
 

Taeian clark

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Suggestions;
Wrapping things up with some of my suggestions and ideals that I implement regarding androgen receptor upregulation for muscle growth and strength gains.

Keep your cycles short, even with long esters. Have a mini-break in between cycles and restart with a new cycle.

Use items that are proven to increase androgen receptor content such as the amino acid L-Carnitine. Which I've had clients use this and report a feeling of being on a high dose cycle of anabolics when they were on a simple HRT dose of anabolic. Or even naturals such as Aaron Curtis who I had suggested using Carnitine, which resulted in him hitting a PR on his deadlift when he had only been getting back into the gym for a short period after an almost 2 year lay off of being very inconsistent. And elite powerlifter Chris Duffin who I also told him to use the supplement carnitine, and out of nowhere his weight had shot up 7lbs after it had been stagnant for a long time and also saw an immense boost to strength as well. So even on top athletes the simple addition of carnitine lead to mind-blowing effects.

The thyroid hormone T3, also a great item for upregulating androgen receptors. A hormone when used properly that has always been known for "enhancing" the effects of a users steroid cycle. And above is the reason why. The addition of T3 thyroid hormone is also great for the fact anabolic steroids tend to decrease thyroid hormone values as much as 20 percent. T3 also plays a large role in protein synthesis on its own.

Carnitine;
"In summary, these data demonstrated that: 1) feeding after RE increased AR content, which may result in increased testosterone uptake, and thus enhanced luteinizing hormone secretion via feedback mechanisms; and 2) LCLT supplementation upregulated AR content, which may promote recovery from RE."
https://www.ncbi.nlm.nih.gov/pubmed/16826026?dopt=Abstract
T3;
"while the in vitro addition of testosterone or T3 or both hormones together augmented the ARs in the cytosol to a greater extent, resulting in an increase in their total (cytosolic and nuclear) content in the cells. The present data suggest that T3 down-regulates ERs and up-regulates ARs in peripuberal Sertoli cells. The additive effect of testosterone and T3 in up-regulating ARs could possibly involve a role for T3 in influencing the androgen responsiveness of the Sertoli cells during spermatogenesis."
https://www.ncbi.nlm.nih.gov/pubmed/8568470

"The up-regulated genes also included nuclear receptor coactivator 4, a coactivator of androgen receptor and peroxisome proliferator-activated receptor (Yeh and Chang 1996)."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC155277/



Conclusion;
Keep your cycles short. This is why I suggest 6 week steroid cycles. Why stay on any longer and waste time for a mere 10 percent benefit when 90 percent of your strength and size gains are seen within the first 6 weeks. Staying on an extra 4 or 6 weeks for a 10 percent benefit when you could have had that time as off time to let your androgen receptors recover from the stimuli of anabolics. And then be back on cycle again by that time, for the immense gains in strength and muscle size anabolics are known for.

And as for more merit to this way of cycling, have a quick search on just how many pro bodybuilders have sworn by this method without even knowing the science but instead going by just their experiences. Kevin Leverone in an article stated he only liked 6-8 week cycles during the offseason. Dorian yates same thing. Ian Harrison stated specifically how he only saw gains during the first 6 weeks of a cycle so why bother staying on any longer and he would rather get off cycle sooner to get back on cycle sooner. Many pros have made such statements but most have always wanted to believe pros cycling for such short durations for growing were flat out lies. Not realizing there is actually science backing their ways that they realized worked by experience alone.
 

madg

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Interesting

After 6 weeks you go off ? What about ppl on trt ?
 

Taeian clark

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Go off or go back onto your TRT. From my experiences the guys who were on TRT even prior to ever running a real cycle and with TRT breaks still have amazing results. Example picture below of a TRT based person after 6 weeks done right. Depending on the ester is your time off. Trust me on the carnitine though, even if on right now. Add it, both forms suggested above. It will feel like you just mega dosed your cycle.

Edit; Pic wont attach
 

hawkmoon

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I just saw the video by MDMD on this; well done.

I don't think anyone is advocating coming totally off at 6 weeks, just progress stops without changing something upward.

Coming off, or dramatically down can re-sensitize as well, but I'd argue if you take a few weeks off and then go back on as Dorian and Ian often reported you need to come back into something more aggressive in some aspect, otherwise you will be repeating your previous progress-loop.

This increase can be food, intensity, or drugs.
TBH I think most of us do this in some way if paying attention anyway. We just refer to it as a plateau and increase food or drugs as needed.

Good to see some science behind the process though, even if not fully understood. Also glad to see that myostatin is not the concrete limiting agent of progress.
 

Taeian clark

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Main part is, many staying on much longer when the anabolic benefits are gone and almost wasting time, only getting a anti catabolic effect. Hence why so many pros seemed to have done this by experience. Use gear whole cut, but off season burst were short for many who have always been open about it. So guys taking their bulks to 12 plus week cycles are wasting a lot of the magic period of steroids. And would be better off like many pros have felt by experience limiting it to 6 week blast. Essentially putting the science here on halting it at 6 week to save people time and get more gains in during their off season by halting at week 6 off sooner to get on quicker.


Not mpmd btw incase that was thought.
 

hawkmoon

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Main part is, many staying on much longer when the anabolic benefits are gone and almost wasting time, only getting a anti catabolic effect. Hence why so many pros seemed to have done this by experience. Use gear whole cut, but off season burst were short for many who have always been open about it. So guys taking their bulks to 12 plus week cycles are wasting a lot of the magic period of steroids. And would be better off like many pros have felt by experience limiting it to 6 week blast. Essentially putting the science here on halting it at 6 week to save people time and get more gains in during their off season by halting at week 6 off sooner to get on quicker.


Not mpmd btw incase that was thought.
Didn't think you were Derek, I just literally watched the video a couple hours ago. ;)

I read Ian's old interview and saw the theory at the time of short cycles and backing off, then repeating.

"I can tell you exactly how I've used gear for the last four years, it's never varied. I've always done six-week cycles, I've always androgen loaded for two weeks, and then used a fast-acting androgen for the last four weeks. Then I've got three weeks to clean out. " - Harrison

I have to question however if three weeks cleared much of anything out.
 

Taeian clark

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Well remember Ian ended with fast ester steroids right. Such as prop which is actually a 0.8 day half life. And we see other parameters return to baseline within 2 weeks such as myostatin. So it seems other areas can return to baseline very quickly.

So adding this in with real world experiances is where I add it all together. Peoples real world experiances on diff time frames and the studies even if some cannot tell us in every area. But bodybuildings always been a sport where experiance is king in those who are successful.
 

madg

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So if doing lets say primo e for 6 weeks , how many weeks off , 4 ?
 

Taeian clark

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So if doing lets say primo e for 6 weeks , how many weeks off , 4 ?
Primo e solo? Assuming your longest ester. Here I prefer 5 to 6 week break. Have done less but feel the extra week or 2 really bumps gains up.

How do I upload pictures from my fb to show some results of others. It won't let me attach files.
 

coma

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You rarely see Taeian mentioned on forums, so it's great seeing this here. Taeian has been preaching this science for years now. I've been doing the 6 on/6 off for a few years. My brother and I spent over a year blasting Deca and Tren, and just got so burnt out. This exact method is the only way we'll do it now. Here's a link to his article posted long before I've seen others talk about it. The few people I've mentioned this method to don't believe me until they try it. Don't forget your potassium! Oh, and check out his Deca Solo article, too. Changed my life

 

raizer

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Interesting

After 6 weeks you go off ? What about ppl on trt ?
About T3! Do you suggest just a replacement dose something like 12,5mcg-25 mcg( because of the 20 procent decrease) or more in the range of 50+ mcg for protein synthesis and upregulation of androgen receptors. If we go by this theory 50 mcg would be a better choise. Do you cut after 6 weeks cycle your T3 out or taper it down and keep it then at replacement dose?
 

Taeian clark

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You rarely see Taeian mentioned on forums, so it's great seeing this here. Taeian has been preaching this science for years now. I've been doing the 6 on/6 off for a few years. My brother and I spent over a year blasting Deca and Tren, and just got so burnt out. This exact method is the only way we'll do it now. Here's a link to his article posted long before I've seen others talk about it. The few people I've mentioned this method to don't believe me until they try it. Don't forget your potassium! Oh, and check out his Deca Solo article, too. Changed my life


Appreciate kind words much.
 

madg

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Primo e solo? Assuming your longest ester. Here I prefer 5 to 6 week break. Have done less but feel the extra week or 2 really bumps gains up.

How do I upload pictures from my fb to show some results of others. It won't let me attach files.
100 mg test , 600 primo , 200 tren hex pet week

6 on /6 off then as i understand ?

Will give this a go seems interesting
 

Taeian clark

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About T3! Do you suggest just a replacement dose something like 12,5mcg-25 mcg( because of the 20 procent decrease) or more in the range of 50+ mcg for protein synthesis and upregulation of androgen receptors. If we go by this theory 50 mcg would be a better choise. Do you cut after 6 weeks cycle your T3 out or taper it down and keep it then at replacement dose?

Ok so. 12.5mcg is shutting yourself down and essentially making yourself hypothyroid. So worsening gains.

Now everyone has thyroid hormone receptor sensivity just like insulin receptor sensivity and androgens. And t3 monotherapy aka no t4 showed 25mcg to be normal was too low dose for many. So I do find 37.5 to 50mcg to be more optimal for most.

As studies on animals for example show us t3 improves muscle gains to a point then lowers. Simply always ensure enough protein namely to ve safe if on higher dose to only enhance gains. The carnitine however remember I said above id what will blow you out of the water trust me try it asap.

T3 requires about 3 weeks recovery coming off. So usually if doing back to back cycles best to stay on replacement dose.
 

DrBeefcake777

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Didn't think you were Derek, I just literally watched the video a couple hours ago. ;)

I read Ian's old interview and saw the theory at the time of short cycles and backing off, then repeating.

"I can tell you exactly how I've used gear for the last four years, it's never varied. I've always done six-week cycles, I've always androgen loaded for two weeks, and then used a fast-acting androgen for the last four weeks. Then I've got three weeks to clean out. " - Harrison

I have to question however if three weeks cleared much of anything out.
Fuckin Derek dude....

Hes become my favorite fitness YTer hands down.

Its very coincidental bc YT suggested me that exact vid about 2 hours ago and I watched it. I saw this and immediately thought of it.

Had me contemplating a little Test Prop action with some NPP maybe for that 40 day mini cycle then back on the Test Enan TRT for 8-12 weeks.

Its one of those things where trying it certainly wouldnt hurt. Im gonna be on TRT or 12-16 weeks of 500mg of hormones. Might need to try this 6 weekish short ester lowish dose cycle and see if after 2-3 the gains seem just as good.
 

Swifto

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I dont think the problem is "AR down-regulation", there is data supporting the opposite actually happens.

I think the problem is not adjusting calories, dealing with fatigue, changing training and diet when people have gained more muscle mass, then assuming their AAS cycle has stalled.

Show me some data that exogenous testosterone or AAS become less effective on anabolic pathways like increased protein synthesis, nitrogen retention and enhanced recovery over time? As I cant recall seeing any.
 

Taeian clark

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100 mg test , 600 primo , 200 tren hex pet week

6 on /6 off then as i understand ?

Will give this a go seems interesting
Yup 5 to 6 off. Likely good with 5 as optimal. Possibly 4 depending how fast you clear hormones
 

Taeian clark

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I dont think the problem is "AR down-regulation", there is data supporting the opposite actually happens.

I think the problem is not adjusting calories, dealing with fatigue, changing training and diet when people have gained more muscle mass, then assuming their AAS cycle has stalled.

Show me some data that exogenous testosterone or AAS become less effective on anabolic pathways like increased protein synthesis, nitrogen retention and enhanced recovery over time? As I cant recall seeing any.
If you read the article you'd see i posted data on everything you just said. Exogenous steroids upregulating aas then receptors returning to baseline. Literally posted and answered everytbing you said with studies. Read it

The studies literally show aas causing enhanced anabolic effects first part of use then causing no more anabolic effects after longer time on. Literally everything your asking is in the article and in the studies.
 

raizer

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Ok so. 12.5mcg is shutting yourself down and essentially making yourself hypothyroid. So worsening gains.

Now everyone has thyroid hormone receptor sensivity just like insulin receptor sensivity and androgens. And t3 monotherapy aka no t4 showed 25mcg to be normal was too low dose for many. So I do find 37.5 to 50mcg to be more optimal for most.

As studies on animals for example show us t3 improves muscle gains to a point then lowers. Simply always ensure enough protein namely to ve safe if on higher dose to only enhance gains. The carnitine however remember I said above id what will blow you out of the water trust me try it asap.

T3 requires about 3 weeks recovery coming off. So usually if doing back to back cycles best to stay on replacement dose.
I was of the same opinion thanx. Now if someone is already using 100 mcg T4 , then 25 mcg would be enough or stil stay on 37,5 mcg T3? and then just go to replacement dose of 50 mcg T4 and 12,5 T3 in the 4 weeks off cycle?
 
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