Kraemer, W. J., & Ratamess, N. A. (2005). Hormonal responses and adaptations to resistance exercise and training. Sports Medicine, 35, 339-361.

This extensive and comprehensive review of the effect of resistance training bouts and programs on hormonal responses in humans provides insights into natural events that could give rise to positive test results in the flawed-WADA testing program.

Testosterone. Testosterone augments other hormonal mechanisms (e.g., human growth factor, insulin-like growth factor-1) in anabolic processes, and effects the nervous system (i.e., it can interact with receptions on neurons and increase the amount of neurotransmitters released, regenerate nerves, increase cell body size, and affect dendrite composition). These latter factors suggest it has a primary role in enhancing force production (p. 341).

Resistance exercise increases total testosterone immediately following exercise in men but not in women [women respond with other anabolic hormones]. The level of increase is affected by the mass of muscle involved, exercise intensity and volume, supplement intake, and training experience, but is independent of an individual's absolute muscle mass. The characteristics of a testosterone provoking resistance workout are high volume, moderate to high intensity, short rest intervals, and the use of large muscle masses. The protocol should provide frequent bouts of glycolytic work. This type of workout stimulation is commonly employed by "natural" body builders. Low repetition workouts do not stimulate excessive testosterone. Post-exercise high protein/carbohydrate supplementation tends to reduce the testosterone response. [In the remainder of this summary, resistance training will be considered to be of the form favored by natural body builders.]

If drug testing occurs in close proximity to the completion of a testosterone enhancing workout, testosterone levels and the testosterone:epitestosterone ratio could be inflated beyond the nanoscopic tolerances allowed in drug testing.

Testosterone Precursors. Testosterone precursors (prohormones) are substances that occur in the various steps of the complex action called the "biosynthetic pathway". It is thought that consumption of precursors would reduce the number of conversion steps and enhance testosterone concentration. The precursors include the banned substances DHEA, androstenedione, and leuteinising hormone (p. 345).

Low doses (50-100 mg/d) of these prohormones do not increase circulating testosterone although their levels are elevated and often accompanied by less desirable estrone, estradiol, and reductions in high-density lipoproteins. Higher doses do not promote consistent responses in resistance training athletes. Only some individuals, those who "respond" to the chemical, show elevations in testosterone. This leads to the possibility of a positive drug test for an individual because of an unusual chemical sensitivity rather than any attempt to cheat.

Androstenedione ("andro") received much attention in the past several years because of its use by some notable baseball players in the USA. Now that research is being published, it does not appear to be the "performance enhancer" initially mythologized and continually reinforced by anti-drugs-in-sport zealots. The majority of andro undergoes hepatic metabolism to testosterone and then to testosterone metabolites prior to release into the circulation. Small to moderate doses of prohormones produce minimal, if any, elevations in testosterone in young men. However, the elevations in testosterone metabolites, estradiol, estrone, and HLD reduction pose health risks and warrant consideration before using prohormones (p. 345). Long-term use of prohormones is not associated with muscle strength or hypertrophy. Since initial strength gains are neural in nature, the role of these prohormones needs to be reassessed. They do not appear to be the "instant performance-enhancers" that is popularly (and with considerable ignorance) proposed today. [When an improvement seems to be associated with ingestion of prohormones, one should consider seriously the role of a placebo effect for causing observable changes.]

Human Growth Hormone Super Family (Growth Hormone Polypeptides). The most commonly assessed form of growth hormone (hGH) is elevated after extensive volumes of resistance exercise, in both genders but is particularly notable in women. The acute response in women compensates for their lower testosterone response to demanding resistance training. The common exercise factor to provoke this response is high volume with high effort on large muscle mass exercises (once again similar to the routines performed by natural body builders). The response is more limited in older individuals, which is likely due to their reticence to work as hard as younger individuals do. Resting levels of hGH and circulating levels of GH-specific binding proteins do not change with resistance training.

As tests for hGH are implemented, testing after an hGH-stimulating workout is likely to place an innocent athlete at risk of recording a false positive, which will be ignored by testing authorities.

Glucocorticoids (Cortisol). Glucocorticoids are released from the adrenal cortex in response to exercise stress. Unlike testosterone and hGH, they are catabolic. Cortisol is 95% of the glucocorticoids produced in the body. In peripheral tissues, cortisol stimulates lipolysis in adipose cells, increases protein degradation resulting in greater release of lipids, and decreases protein synthesis in muscle cells also releasing amino acids into the circulation (p. 348-349).

If an athlete used anabolic steroids, those steroids would reduce cortisol secretion during and after intense resistance exercise. Carbohydrate supplementation also reduces its secretion. A reduction in cortisol presence should result in an increase in the growth response from exercise. Once again, only highly demanding resistance training provokes an elevated cortisol response. The higher the demand, the greater is the response. Moderate training has no effect.

Insulin-Like Growth Factors (IGFs). IGFs are structurally related to insulin and mediate many of the actions of growth hormones. They are small polypeptide hormones produced by the liver in response to hGH-stimulated DNA synthesis. They increase protein synthesis during resistance training and enhance muscle hypertrophy (p. 350). IGF-1 has been studied the most extensively.

IGF-1 elevation may be delayed until hGH-stimulated synthesis and secretion from the liver take place. Chronic elevation of IGF-1 usually does not occur in men but often does in women during high volume training. IGF-1 is reduced during overreaching but returns to baseline upon resumption of normalcy.

Insulin. Insulin has been shown to affect significantly muscle protein synthesis when adequate amino acid concentrations are available, especially by reducing protein catabolism (p. 352). The ingestion of carbohydrates, amino acids, or both before, during, or after resistance exercise will contribute to enhancing insulin's effect of tissue anabolism because they influence its presence more than exercise.

Catecholamines. Catecholamines reflect the acute demands of a resistance exercise protocol and are important for increasing force production, muscle contraction rate, and energy availability, as well as augmenting hormones such as testosterone (p 352). After resistance training, epinephrine, norepinephrine, and dopamine are elevated. Epinephrine and norepinephrine are elevated before intense exercise indicating they are part of a preparatory reaction to an impending exercise challenge

Some hormones are secreted according to a circadian pattern. Measurements will differ depending upon the time of day the assessment is made. Fluctuations are not taken into account in drug-testing increasing the likelihood of a false positive in drug-testing programs.

Generally, hormonal responses to demanding high-volume resistance exercise include increases in the first 30 minutes of recovery in testosterone, hGH, and cortisol. IGF-1 occurs after growth hormones have caused hepatic secretions, and insulin increases in the presence of elevated blood glucose and dietary supplements. Catecholamines are associated with demanding strenuous exercise and appear to be part of a psychophysiological response to high task challenges. These hormonal responses are mostly associated with tissue growth, repair, and reformation and do not appear to be associated with any consistent metabolic change.

Implications. Testosterone, hGH, IGF-1, and cortisol are tested in drug programs. Their elevation is likely to be unacceptable in individuals who naturally have above average resting levels, respond excessively to very demanding resistance training sessions, and are tested very close to exercise completion. To avoid invalid test results, athletes who are required to provide a urine sample after a body-builder-type resistance program should do the following:

Athletes undertaking a muscle building program are likely to be at greater risk for a false positive test after exercise than at any other time, solely because of natural events that do not fall under the exogenous-endogenous classification. The ability of an athlete to train optimally and effectively in resistance programs has to be compromised by the threat of yielding a false positive result in a WADA-style drug test.

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