Skeletal muscle hypertrophy (growth) and androgens go hand in hand.  Unless you’re a genetic, myostatin-blocking mutant, it’s likely that gaining weight and muscle is harder than skydiving without a parachute. OK, maybe not that hard. Testosterone and many of its pharmaceutical derivatives are clearly the most effective of the anabolics (sorry, GH, IGF-1, insulin, etc.). Many androgens can be rightly used for treating wasting disorders, treatment of anemia and prevention of depression resulting from having too-low blood testosterone levels. Of course, some of the more intriguing biological questions surround how testosterone and its derivatives work. That is, what’s the mechanism? 

Androgen receptors, or the AR, are the likely candidates for where you should look to unlock the keys to how androgens exert their many varied effects. In fact, levels of androgen receptor are uniquely sensitive to circulating levels of androgen.1 However, in that study, DHT, or dihydrotestosterone, was administered to rats. DHT is a very androgenic steroid. There are better androgens (i.e., with greater anabolic activity and less androgenic activity).  Thus, scientists from the University of South Carolina sought to elucidate on the mechanisms by which a nandrolone decanoate, also fondly known as Deca-Durabolin or Deca, affected muscles in rats. 

Deca was given to rats at a dose of six milligrams per kilogram (mg/kg) body weight weekly for four weeks. This dose would be equivalent to 545 milligrams of Deca weekly for a 200-pound individual. That’s not what I’d consider a high dose, but certainly one that should exert anabolic effects. The rats getting the Deca were either young (five months) or old (25 months). The researchers found that Deca reduced body fat (measured in the abdomen around the kidneys) in the old rats, but not the young rats. Now, the odd part is that Deca had no effect on muscle weights. This, despite the fact that Deca increased AR protein significantly in both young and old rats. Interestingly, this effect was seen primarily in the slow muscle fiber types found in the soleus muscle (but not the fast-twitch dominant plantaris muscle). 

Past research has shown that slow muscle fibers have a higher DNA concentration and overall satellite cell percentage compared to fast muscles.  Perhaps this makes them more sensitive to androgen administration (when compared to fast muscles). Also, I’d speculate that a much longer administration of Deca (maybe two to three months longer) would have produced a significant hypertrophy of the muscle fibers. (References: J Appl Physiol, 87:2016-2019, 1999; J Appl Physiol, 93:242-250, 2002)

Deca Enhances Biogenic Amines!
There’s a school of thought that believes part of the effect of steroids is related to their action on biochemical changes in the brain. For instance, anabolic steroid treatment for 14 days has been shown to elevate beta-endorphin levels, dynorphin B and met-enkephalin-Arg6Phe in the brain. Also, neurotransmitters such as serotonin, norepinephrine, dopamine and acetylcholine have been shown to have an effect on fatigue and perhaps androgens might affect levels of these chemicals. In fact, the regions of the brain that govern motivation and aggressiveness have been postulated to be impacted by androgens. 

In a group of rats given Deca, scientists found that levels of norepinephrine and its metabolite, 4-hydroxy-3-methoxyphenylglycol, increased. Also, levels of serotonin and its metabolite, 5-hydroxy-indole-3-acetic acid, increased. What does this mean? According to the authors, “…physical performance enhancement after anabolic-androgenic steroid treatment [is] consistent with the interpretation that elevated levels of adrenergic and serotonergic amines in the hypothalamus could contribute to aggressive behaviors as well as improved physical performance.” So, not only do androgens— in this case Deca— directly affect skeletal muscle, they also act at the level of the central nervous system! (Reference: Med Sci Sports Exerc, 35:32-38, 2003)

Lifting Protocols to Maximize Growth Factors?
In an intriguing study done by a group of scientists at the Democritus University of Thrace (in Greece), researchers compared the response of testosterone, cortisol and growth hormone after doing different kinds of weight training workouts: Maximum Strength (MS), Muscular Hypertrophy (MH), and Strength Endurance (SE). The MS protocol consisted basically of two, four or six sets of five reps (three-minute rest interval) for the bench press, lat pulldown, and squat. The MH protocol consisted of two, four or six sets of 10 reps (two-minute rest interval) with the same exercises, and the SH protocol two or four sets of 15 reps (one-minute rest interval) for the same exercises. 

What did they find? Testosterone didn’t change for any of the protocols.  The number of sets didn’t affect hormonal response in the MS protocol.  Cortisol and GH responses were greater after four sets compared to two sets in the MH and SE protocols, with no differences between the six-set and four-set sessions of the MH protocol.

GH seemed to be highest in the SE group when doing four sets of 15 and slightly elevated in the MH group after doing four sets of 10. If you’re as confused as I am, don’t fret. What this all means may be… well… nada.  According to the authors, “the number of sets functions up to a point as a stimulus for increased hormonal concentrations in order to optimize adaptations in the MH and SE protocols, and has no effect on the MS protocol.  Furthermore, the number of sets may differentiate long-term adaptations in MS, MH and SE protocols causing distinct hormonal responses.”  Wow, that’s a mouthful. Here’s my take on the data:

It may not matter because if you engage in periodized training, you’ll likely be doing some semblance of all of these protocols (depending on what time frame you are in in the competitive season). Also, we clearly know that the MS protocol will make you bigger and stronger. Just because you don’t get changes in blood hormones doesn’t mean you won’t get the skeletal muscle adaptations. Remember, growth of muscle fibers is IMO, largely a local phenomenon, meaning you can get muscles to grow in Petri dishes, or in animals that are testosterone-deficient, GH-deficient, etc. Growth is largely a function of high tension generated within each muscle fiber!

So my advice: Do all of the above training sessions. (Reference: Med Sci Sports Exerc, 35:644-654, 2003)