|Image 1: As it turns out, changes within the broad physiological range, have only negligible effects on muscle mass. Their potential negative impact on body fat is yet startlingly pronounced (see also fig. 2)|
More is more, but is more better?
If you took a scrutinizing look at figure 1 from yesterday's installment, you probably will have noticed that quadrupling the amount of testosterone enanthate from 125mg /week to 600mg /week did not quadruple the the amount of lean muscle the subjects gained - or, as an economist would immediately realize, the marginal utility is diminishing!
|Figure 1: Dose response relationship of muscle gain (in kg) per mg of testosterone enanthate; the white line indicates a dose that would probably have produce testosterone levels identical to baseline (calculated based on Bhasin. 2001)|
Surprise, surprise! Slightly below the "natural range" you get the most bang for your... T!
If we take into consideration that the "normal range" for testosterone levels ranges from 300 to 1000 ng/dl and that the subjects in the Bhasin study had baseline levels of ~600 ng/dl, all changes between -50% and +66% would be within what the medical orthodoxy considers "normal" (note: if the subjects already had "low" levels, even changes of +200% would still be within the normal range, please keep that in mind, when you read about the latest and greatest test-boosters ;-):
|Figure 2: Relative change in lean and fat mass in response to changes in serum testosterone levels; the green area indicates "normal" = physiological testosterone levels; the asterisks (*) denote statistically significant (p < 0.05) changes vs. baseline (calculated based on Bhasin. 2001)|
An analysis of the complex interrelations between your beer belly and that which is hidden from your view beneath the former would yet go way beyond the scope of this installment of the Intermittent Thoughts, where testosterone's effects on skeletal muscle, not adipose tissue, are at the center of our attention. And that these effects should obviously not be restricted to increases in "lean mass", but should also be measurable in terms of "size", i.e. muscle circumference / cross-sectional area (CSA), and strength gains, is self-evident.
Does testosterone make you bigger, leaner and stronger?
As those of you who are familiar with the results of any of the 11,000-1 studies on hypogonodal, old or sick patients, where HRT-induced increases in total skeletal muscle mass are oftentimes similarly "statistically insignificant", will probably have expected the researchers would nevertheless not actually have needed an expensive DEXA scanner to see that the muscle mass of their subjects had increased - as the data in figure 3 shows, a simple measuring tape would have been sufficient:
|Figure 3: Relative changes in thigh and quadriceps circumference and maximal leg press strength and power (measured on a Nottingham leg extensor power rig) in response to 20 weeks on different dosages of testosterone enanthate (calculated based on Bhasin. 2001)|
For both the leg press strength, as well as the total leg power, though, a different picture emerges: Contrary to the weight and size gains, the gains in strength and power in the 125mg were not statistically significant (p = 0.42 and p = 0.59). Moreover, the aforementioned effect of "diminishing returns" with doses of testosterone >300mg /week is way more pronounced for leg strength and power than it is for the gains in total muscle mass and leg muscle volume. And as if that was not already confusing enough, in contrast to the +7% increase in the 125mg group, the + 6% increase in leg press power in the "low testosterone" group (50 mg) did reach statistical significance (p = 0.02).
Testosterone, myostatin and IGF-1 - tying the knots together
In order to explain this "strength anomaly", we will have to resort to what we have learned in previous installments of this series about the differential effects of myostatin and IGF-1 on muscle size and composition. Assuming that you have read all the installments of the Intermittent Thoughts, you will be familar with the results from the Quaisar study, I discussed in "What is Hypertrophy". You will also remember that Quaisar et al.'s observations showed quite clearly that the "uncontrolled" muscular hypertrophy in the myostatin negative mice left them with huge, yet dysfunctional muscles. The over-expression of IGF-1 on the other hand, facilitated a profound restructuring process within the skeletal muscle in the course of which the recruitement of satellite cells and the subsequent addition of myonuclei allowed for "healthy" growth that would not burst the maximally allowed myonuclear domain sizes (cf. "Getting Big Means Growing Beyond Temporary Physiological Limits").
|Figure 4: Correlation (R²) of muscle volume and performance with testosterone and IGF 1 (left); testosterone / IGF-1 ratio before and after 20 weeks on different amounts of testosterone enanthate (right; data calculated based on Bhasin. 2001)|
How all this is (or at least researchers believe it is) eventually in fact related to myostatin, how testosterone affects the fast- to slow-twitch fiber ratio (which could explain the anomalous increase in leg strength in the 50mg test E group), mitochondrial biogenesis and satellite cell function, are yet topics that will have to wait until Sunday, when - just as every week - I will sacrifice my free time and write down more Intermittent Thoughts Building Muscle.