The Arguments for Downregulation of ARs

Jul 06, 2020

The Arguments for Downregulation of ARs

Professional athletes and bodybuilders who enjoy using steroids as a way of upping their game and improving their muscle mass are probably familiar with the way steroids work. People who are very much into steroids read a lot about it, in order to find the right measure for using steroids properly and getting the best results out of it. This is why spreading false and unfounded information can be very harmful. An example of such information is the claim that androgen receptors (ARs) tend to downregulate if you start using taking higher doses of steroids. This hypothesis is disproven in practice and it is problematic even in the domain of theory. However, in order to explain why this theory doesn’t hold true, we need to take a look at some frequent arguments used to prove it.

Arguments in Popular Literature

First, we need to take a look at some of the common misconceptions present in the popular literature because this one is read by wide readership and often taken for granted.

One of the arguments say that users of anabolics have elevated levels of androgens, but they have very few testosterone receptors in their muscles. The paradox for natural bodybuilders is the fact they have plenty of receptors but that they don’t have sufficient amount of testosterone.

This argument is simply not verifiable as there are no studies in the literature demonstrating it. The above statement is an assertion only, and therefore cannot be accepted as evidence that steroid use in athletes leads to downregulation the androgen receptors.

Another argument goes like this: Anabolic users have more androgens than they need, so their workout plan should be oriented solely towards re-opening the testosterone receptors.

This argument points to the issue of sensitivity, not of regulation. This claim too is unsupported. Users of anabolic steroids find beneficial and more effective increased doses of androgen. Advanced users may also need all that they are using simply to maintain their far-above normal muscle mass, let alone gain further mass. The argument about re-opening the receptors is confusing as the receptors are not closed. In scientific literature there is no indication that they can be closed under any circumstances, or that there is a cure for treating this completely unknown condition.

There is also a statement which says that the first cycle of steroids always gives the best results because as you keep on using steroids you will either lack testosterone or receptors.

Such argumentation that the first cycle gives the most prominent results is true, but not for the reasons which are frequently added to it. More precisely, the cycle starting at the lowest muscular bodyweight will have the greatest effects on our body. This probably because the closer you are to your untrained starting point, the easier it is to gain muscles. In order to prove this logic let’s imagine a person who achieved excellent development with several years of training without using steroids or any other workout supplements. Then this person decides to try steroids and he gains yet more size with several steroid cycles. Then, he decides to quit training for a longer period of time and shrinks back almost to his original untrained state. If he resumes training and uses steroids, his routine will give more effects than his first steroid cycle. Because his first steroid cycles came at the time when he already had significant muscle mass, they would be less effective than when he started again almost from the scratch. There is no counter inside muscle cells counting off how many cycles one has done. This does not prove upregulation, but it is strong evidence against the permanent-downregulation-which should come if the theory about the benefits from the first cycle were true. However, this example shows that it cannot be true, and such an argumentation cannot support the theory about downregulation. What is true is the fact that the greater the gains one has already made, the harder further gains are. However, this is always true, whether you use steroids or you train without using any supplements.

Therefore, we can conclude that the theory explaining the effectiveness of the "first cycle" cannot explain anything regarding receptors regulation. Regulation is short term phenomenon, operating on the time scale of hours and days. However, if it was permanent or long- lasting, as authors advocating this theory believe, then if steroid use was ceased for a long time, one had to shrink back to a smaller state than was previously achieved naturally, despite constant training. That would be the consequence because one would have fewer active receptors, because many of them were damaged during that very effective first cycle. That, of course, can never hold true and no science can support such claims.

In many articles and forums available online you can also find claims that as a bodybuilder's level of androgens increases, so does the level of testosterone receptors in his muscles. In these articles, testosterone is said to be able to upregulate its receptors in the muscles. Logically, the more testosterone receptors you have, the more anabolic testosterone will be. The result of the above reasoning is that it gives license to all sorts of excesses.

This theory too is quite illogical. If such an argument was true, sedentary people using steroids – for improving cognitive skills and memory, for example -- would become huge. The extra testosterone in the organism would increase the amount of testosterone receptors. Consequently, the anabolic effect of testosterone would become significantly stronger. In practice, people who don’t train and use steroids for other purposes have very limited muscle growth. They rapidly become immune to testosterone's anabolic effect. So, this real-life example cannot confirm receptors upregulation for the obvious reasons.

First of all, no one has stated that weight training is not needed for the steroid-using bodybuilder. Resistance training is proven to upregulate the receptor, for example, and also incentivizes growth in other ways. Therefore, it is logical that those who lead sedentary lifestyle do not gain nearly as much muscle as those train regularly. The argument that steroid use alone, without any workout, will not produce a muscular bodybuilder proves nothing with respect to how the AR is regulated. Also, the concept that upregulation could only exist as an uncontrollable upwards spiral is completely false. Rather, for any given hormone level, there will be a given receptor level.

There is no feedback system, by which this would then lead to yet higher hormonal level, leading to yet higher receptor level in return. There is actually negative feedback, since upregulation of the androgen receptors in the hypothalamus and pituitary in response to higher androgen would cause greater inhibition of LH/FSH production, hence, some reduction in androgen production.

Also, some authors claim that the heaviest steroid users are found among bodybuilders, so in these cases upregulation of androgen receptors can be observed. The androgens would cause their receptors to multiply and get increasingly more potent as time went on.

However, if androgen receptors were truly upregulated that way, steroid users would get their best gains as the time went by, which means near the end of a cycle, not the beginning, and professional bodybuilders who took many steroid cycles would get far better results out of their cycles than people using it for the first time, which is not true.

There is no reason to believe that upregulation becomes more potent with time. Control of regulation is very quick. The theory that receptor activity is can be measured by gains is simply false. The function of the activated androgen receptor is not to give you gains per se, but actually to enhance protein synthesis. This will only result in gains if muscle catabolism is less than the anabolism. As muscle mass becomes greater, so does catabolism. At one moment, under some hormonal and workout stimulus, equilibrium is accomplished, and there are no more gains. With high dosage of steroid this equilibrium point is at a far higher muscle mass than if androgen levels were at normal levels.

The statement that steroids no longer work for professional bodybuilders because they increased their doses, cannot be true. Even after many cycles and while taking very high doses of steroids, while already being very muscular, you can still have the gains, but you will not observe the results as quickly as with the first cycles and with a very insignificant muscle mass.

Moderate dosage of steroids, even though it is sufficient to occupy the receptors, cannot give you anything near the results you can get with high doses of steroids. Since there is only limited number of ARs and at moderate and even low doses they are all occupied, better results cannot be the effect of higher occupancy at higher doses.

Yet another false theory states that if you use certain dosage for a longer period of time, you will need to increase it in order to compensate for the loss of potency.

In practice, professional bodybuilders don’t start losing muscle mass if they continue taking the same dosage. This theory makes a mistake of mixing up gains slowing down or stopping with effects stopping. Actually, we should take into consideration the muscular level we can accomplish by training without supplements and the levels that are possible to reach with steroids, which are much higher. Once we achieve or nearly achieve the possible levels with the workout/supplement routine we are on at the moment, gains slow down or stop completely. Additionally, even if the body has not yet achieved the higher mass that is possible with a given dosage of steroids, it is harder for many reasons for the body to continue growing after it has recently grown significantly. It needs some time to rest before it is ready to grow a bit more. This phenomenon is expected for people who take steroids and for people who never took any supplements. It is simply the way our body works. Authors who claim that downregulation of AR ensues after the initial cycle, then must believe that downregulation of AR happens even without taking any supplements, since the gains slow down after a couple of months of natural training too.

Another prominent false theory states that androgen upregulation happens in all the muscle cells throughout our body and not just in exercised muscles.

You don’t need to be a scientist to know that this is not true. Imagine if this statement actually held true. If you don’t like doing your legs, you could simply skip all leg trainings, take your steroid dosage and train your arms. Your muscle leg would simply follow and look perfectly trained because you did your biceps training. Unfortunately, this is not how steroids work, and this theory is easily refuted by science as well as real-life experience of bodybuilders. Training together with AAS use is needed to shape your body beyond the limits of natural training. Use of steroids alone is not sufficient. If steroids work without the training, you would just need to take AAS while watching TV and your muscles would be getting bigger and bigger every day.

Yet another popular statement which argues that potency of steroids gets lost simply because certain period of time passed goes like this-The muscle fights the excess and immunizes itself against androgens, which is the main reason why steroids become less potent over time.

The statement that the body immunizes itself against androgens is incorrect form the scientific and medical standpoint. Since such an argument cannot be proven either in practice or by facts, it has to be thrown away as one of the unfounded theories circling around some popular magazines and blogs.


If you read about steroid consumptions online, you will come across many theories and statements which are simply false. Many of them will state that androgen receptors, very important for processing steroids, simply downregulate as the time passes. Based on these theories, this process leads to steroids losing potency, and gains slowing down or completely ceasing after a period of time. Luckily, this is not how steroids work. Gains do slow down, but because there is a limit to what you can accomplish with certain type of workout and steroid doses. Higher steroid doses don’t cause downregulation, and they are necessary for acquiring beyond-natural muscle mass that bodybuilders have.

• Dec 28, 2020