Wednesday, July 13, 2016

Excessive Cardio & Testosterone: The free T / Cortisol Ratio Revisited | Plus: Why Even a 72% Decrease in fT/C May be Less Significant for Your Gains Than You Thought It'd Be

Cardio - Only "too much" can hurt you.
Let me get this straight: this is not an anti-cardio article. There's not just little, there's rather absolutely no doubt that a sane amount of endurance training is nothing but healthy for us, but done in excess, especially "running has been demonstrated to provide a large physiological stress to the body, resulting in large neuroendocrine system responses" (Anderson. 2016) - more specifically, running to exhaustion will have the hypothalamic–pituitary–adrenal (HPA) axis overproduce the glucocorticoid hormone, cortisol, which in turn appears to suppress the production of testosterone.

Now, cortisol - you've learned that in previous articles - is not the villain as which it is portrait by companies that are trying to sell you useless and potentially counter-productive "cortisol blockers". Rather than ruining your results, normal amount of cortisol will aid in substrate mobilization (including the use of body fat during your workouts) and can even improve your running performance.
You can learn more about overtraining and checking your training status at the SuppVersity

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Surprised? Well, I guess you will be likewise surprised to hear that the well-established connection between high cortisol and low testosterone levels that are characteristic of overtraining is likewise not as black-and-white as you may have heard. In 2005, for example, Brownlee et al. were able to show that the significant decline in total testosterone in response to exercise goes hand in hand with a disassociation of testosterone and its binding globulin SHBG that triggers an increase in free and thus bio-active testosterone levels - an increase that correlates with the exercise-induced increase in cortisol (as Brownlee et al. point out this is probably due to "an adrenal cortex contribution of fT or disassociation of fT from sex hormone binding globulin" | Brownlee. 2005).
Figure 1: Free testosterone and cortisol in young mend during recovery from 60-90min intense exercise (Brownlee. 2005).
In that, it is important to acknowledge that this finding of which the scientists rightly say that it "would seem to support the notion that the observed testosterone reductions following certain forms of physical exercise could be related to cortisol elevations in response to that exercise" does not "indicate a cause and effect relationship" (Brownlee. 2005).
What are the limitations of the study at hand? Next to a too limited (to fully grasp the time-course of the fT / cortisol response after exercise) number of blood draws and the small sample size that did not suffice to confirm the significance of the 24- and 24-h post hormonal changes (this would have required N = 16 subjects), the study at hand shares a general limitation with other studies: it fails to expand its analysis beyond the regular fT : cortisol ratio and into the realm of additional neuroendocrine biomarkers (e.g., prolactin, growth hormone, catecholamines), of which Anderson et al. (2016) rightly point out that they me of particularly importance in women and could vary and eventually determine the fitness-related differences in the hormone response we see in trained vs. untrained athletes.
What it does do, however, is tell us that we cannot restrict post-workout hormone essays to cortisol and total testosterone - unfortunately, the many currently available studies do just that... and what's more: they also fail to "assess the time course required for the neuroendocrine system to return to a resting homeostatic state" (Anderson. 2016) - even though
"[s]uch information is potentially vital to the coach and athlete in establishing timeline guidance forthe number of rest days necessary after strenuous exercise, such as might occur in a competition" (Anderson. 2016).
It is thus only logical that Travis Anderson and colleagues conducted a study to assess
the dynamics (!) of cortisol and testosterone concentration during recovery, following an exhaustive exercise bout. A study the results of which gain significance to the researchers' choice of subjects.
Table 1: Subject characteristics - Certainly not a bad thing to use elite athletes instead of noobs (Anderson. 2016).
12 elite endurance runners who reported to the laboratory on seven separate occasions each time being required to adhere to the preassessment guidelines, which included being 2.5 h fasted, abstaining from strenuous activity, alcohol and sexual activity for 24 h, and abstaining from caffeine consumption for 12 h.
Table 2: Exhaustive exercise session (X ± SD) | VO 2 oxygen uptake, HR heart rate, RPE rate of perceived exertion, VT ventilatory threshold (Anderson. 2016).
Following a 7-day wash-out period, participants took part in a standardized exhaustive exercise test -- a prolonged exercise run on the treadmill until volitional fatigue, running at 100 % +/-3% (see Table 3) of their pre-determined ventilatory threshold (VT | ventilatory threshold refers to the point during exercise at which ventilation starts to increase at a faster rate than VO2, the VT thus reflects the levels of anaerobiosis and lactate accumulation).

Complete exhaustion is key to the ill effects of "cardio"
To ensure "a truly fatiguing exercise session", strong "verbal encouragement" was given to subjects towards the end of the exercise session (the RPE levels in Table 2 indicate that this worked - the subjects, elite athletes or not, were truly exhausted) after which the subjects completed a ~5 min cool down, prior to a post-exercise blood sample being taken (+0 h).
Figure 2: Free testosterone (left, top), cortisol (left, bottom) and fT:cortisol ratio (right | Anderson. 2016).
Subjects reported back to the laboratory at the same time of day 24 (+24 h), 48 (+48 h), and 72 (+72 h) hours after the exhaustive exercise bout, where blood samples were again drawn. Subjects
were asked to maintain a similar diet and activity level compared to the pre-EES period during this 72 h of recovery, and the latter involved only activities of daily living and no exercise training. The analysis of these samples revealed the following results:
  • free testosterone - as far as fT is concerned the researchers observed a significant decrease in fT following EES compared to pre-EES time points (−48 to 0 h; p = 0.053 to p = 0.001) that persisted for up to +48 h into recovery, before returning to baseline (pre-EES) levels at +72 h,
  • cortisol - the scientists' REPANOVA and post hoc analysis revealed increases and decreases in C following EES compared to pre-EES. At +0 h, C was increased (p < 0.001) and decreased at +24 h (p < 0.002) before returning to baseline (pre-EES) levels,
  • free testosterone : cortisol ratio - the analysis of the ratio of the two measured hormones revealed significant differences with post hoc analysis showing fT:C was significantly decreased at +0 h (0.167 ± 0.084) relative to all other time points (p < 0.005), interestingly enough, it took only 24h for the fT:C to return to pre-EES, with no significant differences between +48 h or +72 h compared to any pre-EES values,
With the increase in cortisol being - as preciously hinted at and discussed at length in "All About Cortisol" | read it) - indicative of an increased use of alternative (=non-glucose) substrates, it is not surprising that the intense exercise session, despite being conducted out of the "fat burning zone", did not affect the subjects' glucose concentrations at any measurement time. How's that significant? Well, previously, scientists have speculated that the reduction in testosterone and increase in cortisol could be a stress response to hypoglycemia (=low blood glucose levels). With the study at hand demonstrating stable blood glucose levels, this hypothesis must be refuted. 
Figure 3: Changes in testosterone (top) and T/C values (bottom) of Rugby players during the rest day (black bars), during the competition day (grey bars) and during the postcompetitive recovery period at 8 am and 8 pm (white bars | Elloumi. 2003)
Could HIIT actually increase your testosterone levels in the long(er) run? One interesting artifact the researchers found when reviewing the existing literature on the effects of exercise on (free) testosterone was the sign. increase in testosterone Elloumi et al. observed in the 6 days after an intense rugby match. What speaks against this theory, however, is the fact that Morville et al. have observed a similar increase in T in response to a 100km run in a 1979 study.

Against that background, Anderson's assumption that high-intensity, intermittent nature exercise would elevate, not lower the levels of testosterone during recovery, despite being in line with research in Wrestlers (Passelergue. 1999), appears to be questionable and I would recommend not to try to use high intensity interval (HIIT) training (of all) as a means of increasing your testosterone levels.
As Anderson et al. point out, the results of the study at hand also conflict with previous research suggesting significantly shorter recovery times for the fT:cortisol ratio, namely 38 h and 24h in Rugby and soccer players (after matches | Cunniffe et al. 2010; Ispirlidis et al. 2008).

Eventually, the study at hand therefore supports the previously voiced hypothesis that there may be a mechanistic link between increased cortisol and decreased testosterone levels - a mechanism that has been confirmed for orally ingested cortisol, which resulted in testosterone suppression without changes in follicle-stimulating hormone or luteinizing hormone as early as in 1976 (Doerr. 1976).
Overall, the existing evidence can thus be said to suggests that glucocorticoids will directly suppress steroidogenesis at the level of the Leydig cells, where LH and will no longer do its testosterone production triggering magic when your testes are bathing in cortisol - how the previously discussed increases in free testosterone fit in here, however, requires further research.

One important last finding I would like to discuss before wrapping it up is the (also previously observed | Kraemer. 2009) time-lag between the decline in cortisol and the recovery of testosterone levels. In fact, previous studies in athletes indicate that cortisol will be depressed during recovery. Now, acutely, this may be considered what Cunnife et al. (2010) call a "rebound anabolic stimulus" stimulus during recovery - in the long run, however, a suppressed diurnal cortisol rhythm is one of the hallmark features of overtraining that contributes to its ill effects on both overall well-being and physical performance.
Bottom line: No, cardio is not the devil and cortisol is not always bad for you. In fact, the almost oscillating nature of the individual hormone recovery dynamics in the 48 h postexercise, prior to returning to pre-exercise values clearly supports "the hypothesis that a negative relationship only exists between these hormones when cortisol is significantly elevated (>160 % of baseline values) | Brownlee et al. 2005)" (Anderson. 2016) - with the rapid clearance of cortisol from the bloodstream during the recovery period rendering its effects void within only 24 h of recovery from an exhaustive exercise bout.

Figure 4: Correlations between acute GH, free testosterone, IGF-1 and cortisol responses (area under the curve—AUC) and gains in lean body mass (n = 56). Cortisol AUC was correlated with LBM (r = 0.29, P = 0.03 | West. 2010).
Furthermore, we should not forget that the assumption that the fT or total T to cortisol ratio was a reliable marker of anabolic / catabolic state in the hours and days after a workout is, much in contrast to what the average bro-article on bodybuilding websites would suggest, not backed by science. Rather than that, studies such as may favorite large-scale + long-term resistance training study by West et al. (2009 / 2012) indicate that (a) the transient increases in endogenous purportedly anabolic hormones do not enhance fed-state anabolic signalling or MPS following resistance exercise (West. 2009) and (b) the post-exercise increase in the allegedly catabolic hormone cortisol even correlates with the extent of the 12-week skeletal muscle hypertrophy response to resistance training in 56 young men.

It should be obvious that this does not mean that you should aim to chronically elevate your cortisol levels, but I'd hope that the profound decline in testosterone in response to exhaustive (cardio) exercise is not the only information you take away from today's SuppVersity article. After all, the full recovery of fT within only 24h is of equal if not greater importance when it comes to the allegedly negative effects of sane amounts of cardio training on hormonal parameters of which we assume, but don't know that they determine our training success | Comment!
  • Anderson, Travis, Amy R. Lane, and Anthony C. Hackney. "Cortisol and testosterone dynamics following exhaustive endurance exercise." European journal of applied physiology (2016): 1-7.
  • Cunniffe, Brian, et al. "Time course of changes in immuneoendocrine markers following an international rugby game." European Journal of Applied Physiology 108.1 (2010): 113-122.
  • Doerr, P., and K. M. Pirke. "Cortisol-induced suppression of plasma testosterone in normal adult males." Acta Endocrinologica 80.1 Suppla (1975): S55-S55.
  • Elloumi, M., et al. "Behaviour of saliva cortisol [C], testosterone [T] and the T/C ratio during a rugby match and during the post-competition recovery days." European journal of applied physiology 90.1-2 (2003): 23-28.
  • Ispirlidis, Ioannis, et al. "Time-course of changes in inflammatory and performance responses following a soccer game." Clinical Journal of Sport Medicine 18.5 (2008): 423-431.
  • Kraemer, William J., et al. "Recovery from a national collegiate athletic association division I football game: muscle damage and hormonal status." The Journal of Strength & Conditioning Research 23.1 (2009): 2-10.
  • Passelergue, P., and G. Lac. "Saliva cortisol, testosterone and T/C ratio variations during a wrestling competition and during the post-competitive recovery period." International Journal of Sports Medicine 20.02 (1999): 109-113.
  • West, Daniel WD, et al. "Resistance exercise‐induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men." The Journal of physiology 587.21 (2009): 5239-5247.
  • West, Daniel WD, and Stuart M. Phillips. "Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training." European journal of applied physiology 112.7 (2012): 2693-2702.