How Testosterone improves performance in every one

Muscle
Central nervous system
Erythropoiesis

Muscle. 

Since the discovery of T and the synthesis of

the first androgen, the effects of androgens on body

composition and lean body mass have been extensively

studied and described [1]. Very briefly, the

T-induced increase in skeletal muscle mass is associated

with hypertrophy of both type I and type II

fibers as well as an increase in the number of myonuclei

and satellite cells. T promotes the differentiation

of mesenchymal multipotent cells into the

myogenic lineage and inhibits their differentiation

into the adipogenic lineage. T reduces fat mass by

inhibiting preadipocyte differentiation into adipocytes.

This hormone also increases muscle protein

synthesis and improves the reutilization of amino

acids by the muscle.

T alters neurotransmission at the neuromuscular

junction through a modulation of the choline

acetyltransferase [18], and also influences the

number of acetylcholine receptors at the neuromuscular

junction [19].

Erythropoiesis. 

When addressing the issue of the

ergogenic effects of androgens, the erythropoietic

effects of these hormones or drugs are often neglected.

One should, however, remember that androgens

were largely used in patient with chronic renal

failure or bone marrow failure, before the availability

of synthetic erythropoietin (EPO). Moreover,

increased oxygen-carrying capacity is associated

with greater success rate in sports where the performance

significantly relies on oxidative metabolisms.

Although not fully understood, it is likely

that the erythropoietic effect of androgens relies on

several explanations; stimulation of the renal

secretion of EPO through unknown mechanisms,

suppression of hepcidin levels, increase in iron utilization

for erythropoiesis, and induction of a rightward

shift in the EPO–hemoglobins relationship

curve. This last point is of particular importance

when the sex-related difference in hemoglobins is

considered. Indeed, men and women have similar

EPO reference ranges, but different hemoglobins

concentrations. Hence, an increased T concentration

(endogenous or exogenous) in some female

athletes could set a new equilibrium point on the

EPO-hemoglobins curve, attesting to an increased

EPO sensitivity [20]. In both genders, androgens

increase 2,3-diphosphoglycerate in erythrocytes

which decreases the hemoglobins-oxygen affinity,

thereby facilitating of oxygen release and delivery to

the tissues [21]. Recently, Karunasena et al. [22&]

demonstrated that androgen levels in women with

congenital adrenal hyperplasia are positively associated

with hemoglobins and hematocrit levels.

According to their calculated linear regressions,

increasing circulating T level from 1.5 to 15 nmol/

L, by manipulating the glucocorticosteroid treatment,

would result in an 11 g/L increase in hemoglobins

concentration. A hemoglobins increase of a

similar magnitude, associated with a 3% improvement

in 10km running performance, has been

reported 4 weeks after administration of 50 IU/kg

body mass of recombinant EPO [23].

Central Nervous System. 

Last but not least, androgens also exert their performance-enhancing effects through the central nervous system. At the

spinal cord level, there is growing evidence, mostly

fromanimal studies, that T, like IGF-1, influences the

form and function of the motoric system in humans

[24]. These reported increased cell excitability, attenuated

atrophic changes, and improved regenerative

capacity of motor neurons, which could also account

for the observed improvement in muscle growth and

strength following androgens administration. At

the brain level, sex differences have been observed

regarding cognitive abilities, regional brain structures,

and functions. There are also sex differences

in spatial abilities as measured with the mental

rotation task (MRT), where males have an advantage

over females. This difference, which is found across

the entire life span, is of critical importance since the

performance at theMRTis associated with the type of

sports practiced and the level of expertise. In a recent

study, including nonathletes, orienteers, gymnasts,

and endurance runners, Schmidt et al. [25], while

confirming the known gender difference [26],

showed that athletes outperformed nonathletes at

the MRT. Interestingly, athletes with high mental

rotation demand like gymnasts (egocentric transformation)

and orienteers (allocentric transformation)

showed the best results at the MRT.

Recently, a step has been taken in understanding

the sexual differentiation of visuospatial neural activation.

By using functional MRI assessment, two

research groups [27&,28] showed a female-like activation

pattern in mental rotation-related brain areas

in individuals with complete androgen insensitivity

syndrome, indicating that the sexual differentiation

of visuospatial neural activation is not directly influenced

by sex chromosomal composition, but is determined

by androgens rather than estrogens exposure.

Whilst it appears that long lasting androgens

exposure during childhood or adulthood improves

spatial abilities, as seen for instance in congenital

adrenal hyperplasia female patients [29], the possible

facilitating effect of shorter exposure to androgens is

still investigated in females [30].

Aggressive behavior and risk taking, which are

important determinants of sports performance, are

more frequent in individuals exposed to androgens.A

recent study [31&] investigated the structural covariance,

that is, the examination of anatomic correlations

between the amygdala (a brain area related

to augmented aggressive behavior when stimulated)

and the prefrontal cortex (a regulating area); two

brain areas with the highest density in androgen

receptors. Experiments showed that lower T levels

were associated with a positive covariance between

the amygdala and cortical thickness of this prefrontal

region,whereas higher T levels were associated with a

negative correlationbetweenthese tworegions resulting

inmore aggressive behavior. This work shows how

T targets the neural circuits regulating affects and

impulses independent from sex, age, estradiol, and

pubertal stage, from childhood to adulthood.

Androgens

Volume 24  Number 3  June 2017

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