Hard Gainer? Blame Your Androgen Receptors
Day after day, week after week, you hit the gym, lifting heavy, training with intensity, using the right exercise, and pushing for overload. You also make sure to eat enough protein and consume ample amount of calories to support your muscle-building efforts. And, to top it off you even get 8-9 hours of sleep each night.
Yet, month after month, you fail to see significant progress from your hard work. Still, you’re not deterred. Instead, you double your efforts. Meticulously tracking training, nutrition, and sleep. You even shell out some dough for the best muscle-building supplements, backed by numerous clinical studies, to help bring the gains.
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Alas, after months and months you still struggle to put on slabs of lean muscle mass. Yet, your friend, who trains with crappy form and horrible exercise selection, and lives on a diet of fast-food burgers and fries puts on mass simply by stepping up to the squat rack.
Did you do something to piss off the almighty granter of gains? Were you delinquent in your offerings at the altar of iron? Are you not using the right training program for your body type? Or, do you have low testosterone levels, high estrogen levels, and poor insulin sensitivity?
According to some new research, it’s none of these factors. The reason you struggle to put on mass while your friend can do it with ease, revolves around your androgen receptors.
What are Androgen Receptors?
As many of you probably know, androgens are male sex hormones, such as testosterone, dihydrotestosterone (DHT), androsterone, and Dehydroepiandrosterone (DHEA), that give men their “manly” characteristics.
Androgen receptors (AR) are the “docking bays” for androgens, that become activated when an androgen, such as testosterone, binds to it setting off a cascade of physiological processes that lead to protein synthesis. 
It’s commonly believed that the post-exercise increase in circulating anabolic hormones (e.g. testosterone) is what predicts and determines how responsive an individual is to resistance training, regarding hypertrophy. [3,4]
However, a new study by a group of researchers, including noted protein guru Dr. Stu Phillips, indicates that it isn’t so much how high or low these levels are that determines whether you are a low responder (“hardgainer”) or high responder to resistance training, but your androgen receptor content.
So, let’s look at the study and see what Dr. Stu and the gang discovered.
Dr. Stu and crew examined levels of circulating hormones and intramuscular hormones as well as intramuscular hormone-related variables in previously trained men before and after 12 weeks of resistance training. Specifically, researchers analyzed levels of:
- Free testosterone
- Dihydrotestosterone (DHT)
- Insulin-like growth factor-1 (IGF-1)
- Free insulin-like growth factor-1
- Changes in lean body muscle mass caused by resistance training
Based on the results, researchers grouped the men into one of two categories:
- High responders (HIR), or
- Low responders (LOR), what we commonly refer to as “hardgainers”
Interestingly, at the end of the 12 weeks, researchers observed that there were no differences in intramuscular testosterone or DHT between the high responders or low responders. So, they set out to determine what was the cause between certain individuals gaining more lean mass than others.
What they found out was that androgen receptor content was significantly higher both pre- and post-intervention in the high responders than the low responders. Therefore, researchers concluded that the amount of androgen receptors an individual has, not the levels of circulating hormones post-exercise, is the rate-limiting step on the anabolic effects of resistance training. 
In fact, during the analysis, researchers noted a clear linear relationship between androgen receptor content and change in lean body mass. 
“Androgen receptor content was unchanged with RET but was higher at all times in HIR. 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.” 
One important thing to note is that resistance training did not increase the number of androgen receptors. High responders had higher levels pre and post-intervention.
Based on the findings, the team of researchers concluded:
"These results indicate that intramuscular androgen receptor content, but neither circulating nor intramuscular hormones (or the enzymes regulating their intramuscular production) influenced skeletal muscle hypertrophy following RET (resistance training) in previously trained men." 
In other words, you either got “it” or you don’t, as your ability to gain muscle is directly related to the number of androgen receptors you have.
These findings are in line with previous work by Dr. Stu and others. [5,6]
So, what does this mean for the average gym bro struggling to make gains?
This study helps provide clarity as to why two people can perform the exact same weight training routine, diet, and sleep, yet experience vastly different results. Whereas bro A gains slabs of lean muscle following his diet and training program, bro B struggles to make even the most humble of gains due to his lack of androgen receptors.
If you are a hardgainer, does this mean that you can throw your hands up, and say, “f*** it” to training hard, dieting properly, and sleeping adequately?
You still need to train for overall health and longevity. And, while you may have a “low” androgen receptor content, you’re not completely devoid of them. So whil, your gains may be slow and hard to come by, you still can make them.
There have been several means suggested for increasing androgen receptor density and sensitivity, including:
- Supplementing with L-Carnitine L-Tartrate (1-2g/day). However, more research is needed before the LCLT-androgen receptor density link can be cemented. Plus, if you think about it, if there was a natural compound that increased androgen receptor density, it probably would have been patented by a drug company to be used in hospital settings to treat individuals with muscle-wasting diseases.
- Intermittent fasting. 
- Electroshock therapy.  But this study was in rats, and I don’t know how many casual gym goers are willing to sign up to have their muscles zapped just to make some bigger gains.
- Supplementing with forskolin. 
What about Exogenous Testosterone?
While this study, showed that circulating hormones levels had little to with how much size individuals gained. This doesn’t mean having high levels of anabolic hormones won’t help. In fact, the research is pretty clear that exogenous testosterone is damn effective for adding muscle.
This is due to the fact that exogenous testosterone creates round-the-clock elevations in testosterone levels, whereas exercise only boosts T-levels a maximum of 30-50%, and for only about 30 minutes at most. 
EVen then, if two IFBB pros are taking the same dose of testosterone, yet one has substantially more androgen receptors than the other, he still might make better gains, on account of his increased androgen receptor content. Remember, androgen receptors, not hormones, are the rate-limiting step. Regardless of how much “stuff” you cram into a funnel, if the hole is only so big, only so much is going to flow through at any given time.
High responder or low responder, don’t let these results deter you from getting in the gym and giving it your all each and every session. Even the lowest responder can still make gains. And remember, fitness is a journey, not a destination.
1) Morton, R. W., Sato, K., Gallaugher, M. P. B., Oikawa, S. Y., McNicholas, P. D., Fujita, S., & Phillips, S. M. (2018). Muscle Androgen Receptor Content but Not Systemic Hormones Is Associated With Resistance Training-Induced Skeletal Muscle Hypertrophy in Healthy, Young Men . Frontiers in Physiology . Retrieved from https://www.frontiersin.org/article/10.3389/fphys.2018.01373
2) Davey RA, Grossmann M. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clin Biochem Rev. 2016;37(1):3-15.
3) Kraemer, W. J., Ratamess, N. A., and Nindl, B. C. (2017). Recovery responses of testosterone, growth hormone, and IGF-1 after resistance exercise. J. Appl. Physiol. 122, 549–558. doi: 10.1152/japplphysiol.00599.2016
4) Mangine, G. T., Hoffman, J. R., Gonzalez, A. M., Townsend, J. R., Wells, A. J., Jajtner, A. R., et al. (2017). Exercise-induced hormone elevations are related to muscle growth. J. Strength Cond. Res. 31, 45–53. doi: 10.1519/jsc.0000000000001491
5) Mitchell CJ, Churchward-Venne TA, Bellamy L, Parise G, Baker SK, Phillips SM. Muscular and systemic correlates of resistance training-induced muscle hypertrophy. PLoS One. 2013;8(10):e78636. Published 2013 Oct 9. doi:10.1371/journal.pone.0078636
6) Ahtiainen, J. P., Hulmi, J. J., Kraemer, W. J., Lehti, M., Nyman, K., Selanne, H., Hakkinen, K. (2011). Heavy resistance exercise training and skeletal muscle androgen receptor expression in younger and older men. Steroids, 76(1–2), 183–192. https://doi.org/10.1016/j.steroids.2010.10.012
7) Kraemer, W. J., Spiering, B. A., Volek, J. S., Ratamess, N. A., Sharman, M. J., Rubin, M. R., Maresh, C. M. (2006). Androgenic responses to resistance exercise: effects of feeding and L-carnitine. Medicine and Science in Sports and Exercise, 38(7), 1288–1296. https://doi.org/10.1249/01.mss.0000227314.85728.35
8) Rojdmark, S., Asplund, A., & Rossner, S. (1989). Pituitary-testicular axis in obese men during short-term fasting. Acta Endocrinologica, 121(5), 727–732.
9) Inoue, K., Yamasaki, S., Fushiki, T., Kano, T., Moritani, T., Itoh, K., & Sugimoto, E. (1993). Rapid increase in the number of androgen receptors following electrical stimulation of the rat muscle. European Journal of Applied Physiology and Occupational Physiology, 66(2), 134–140. https://doi.org/10.1007/BF01427054
10) Nazareth, L. V, & Weigel, N. L. (1996). Activation of the human androgen receptor through a protein kinase A signaling pathway. The Journal of Biological Chemistry, 271(33), 19900–19907.
11) Schroeder, E. T., Villanueva, M., West, D. D. W., & Phillips, S. M. (2013). Are acute post-resistance exercise increases in testosterone, growth hormone, and IGF-1 necessary to stimulate skeletal muscle anabolism and hypertrophy? Medicine and Science in Sports and Exercise, 45(11), 2044–2051. https://doi.org/10.1249/MSS.0000000000000147