Anabolics Flashcards
Anabolics and why they are used
Anabolics include androgenic steroids, growth hormone, beta-s AR agonists and myostatin inhibitors.
Lance Armstrong banned for life for using nandrolone, a synthetic testosterone.
Atheletes are trying to increase power, the rate at which they can generate force. The higher the power the larger the acceleration.
Fast muscle fibres generate a much higher power output than slow fibres, but they fatigue more rapidly.
Elite sprinters are born with a large proportion of fast fibres. This distribution of fibres cannot be changed through training. The only way to change this is by taking anabolic drugs.
Anabolics also increase muscle mass. The bigger the change in lean muscle mass, the larger the increase in strength.
Anabolic agents are prohibited at all times, in and out of competition. This includes anabolic androgenic steroids (AAS) and other anabolic agents.
Selective androgen receptor modulators (SARMs) can be targeted to skeletal muscle, reducing systemic side effects.
Anabolic androgenic steroids bind to muscle androgen receptors, resulting in a cascade of cell signalling that increases DNA transcription and muscle protein synthesis.
Testosterone also activates satellite cells. These are quiescent mononucleated muscle stem cells essential for muscle growth, maintenace and regeneration, particularly after injury, as they contribute myonuclei to the growing muscle fibres. They proliferate when activated, increasing the number of nuclei in muscle cells, and also join with existent muscle fibres and form new fibres.
This increases performance.
Cyclists still take anabolics as these drugs also reduce fat mass - they do not want extra weight to carry around, so the goal is to reduce the mass of tissue that is redundant in terms of their performance.
Muscle hypertrophy and myogenesis
In steroid-using powerlifters, the number of muscle fibres with internal myonuclei reaches 25% in trapezius muscle (shoulder) and 29% in vastus lateralis (outer side of the thigh). In non-steroid-using powerlifters, the number of fibres with internal myonuclei is 5% and 9%, respectively.
Testosterone is therefore associated with a 3-5x increase in centrally located myonuclei in the vastus lateralis and trapezius, respectively.
The presence of internal myonuclei is recognized as an indication of ongoing muscle regeneration.
Anabolics may have therapeutic benefit in restoring muscle mass in the elderly.
Changes in fat-free mass (FFM) and skeletal muscle mass in response to testosterone enanthate were measured in young and old men. There was a dose-response effect in the change of FFM, and there is no significant difference between age groups.
There was a small reduction in fat mass, and his was more pronounced in older individuals at lower concentrations, but there was no difference between age groups at higher concentrations.
Strngth increased in both age groups, but more in younger individuals.
There is a consensus that testosterone administration is anabolic, having hypertrophic and myogenic effects.
Older men are not as responsive as young men to testosterone’s anabolic effects.
Although substantial gains in muscle mass and strength can be realized with supraphysiological testosterone doses, these high doses are associated with a high frequency of adverse effects.
The best trade-off was achieved with a testosterone dose of 125 mg, which was associated with high normal testosterone levels. This showed a low frequency of adverse events, and significant gains in fat-free mass and muscle strength.
The effect on fat mass is not overtly apparent.
Side effects of anabolic steroid abuse
Side effects of anabolic steroids are wide-ranging and well reported.
Physical effects of anabolic steroids in men can include: reduced sperm count, infertility, shrunken testicles, erectile dysfunction, baldness, breast development, increased risk of prostate cancer, severe acne, stomach pain.
Effects in women include: facial and body hair growth, loss of breasts, swelling of the clitoris, deepened voice, increased sex drive, period problems, hair loss, severe acne.
Acute medical effects include: heart attack, stroke, liver/kidney failure, fluid retention, hypertension, high cholesterol.
Psychological effects can include: aggressiveness, mood swings, paranoia, manic behaviour, and hallucinations and delusions.
These side effects were the catalyst for the development of selective adrenergic receptor agonists by the pharmaceutical industry.
Growth hormone
Prohibited at all times.
Growth hormone (GH) has become increasingly popular as a doping agent but the precise mechanisms behind the ergogenic (performance enhancing) effects in athletes are still being debated.
Athletes believe that GH increases myofibrillar protein synthesis, but the evidence for this is not robust, and effects seem to be more directed towards the synthesis of connective tissue in muscle and tendons. Given the importance of the connective tissue for the function of skeletal muscle and tendon, a strengthening effect of GH on connective tissue could fit with the ergogenic effect of GH experienced by athletes.
High treatment doses of GH might cause a number of side effects including: carpal tunnel syndrome, insulin resistance and type 2 diabetes, oedema in the arms and legs, joint and muscle pain, enlarged breast tissue in men (gynecomastia), and increased risk of certain cancers.
Beta-2 agonists
All selective and non-selective beta-2 agonists, including all optical isomers, are prohibited at all times. There are some exceptions, allowing certain doses of salbutamol, formoterol, salmeterol and vilanterol in athletes with asthma or other respiratory diseases.
Beta agonists induce bronchodilation, increasing oxygen delivery to the lung.
A common misconception about beta 2-agonists is that, at high doses, they increase muscle mass and decrease fat mass, but these claims are not substantiated.
What has been demonstrated is that chronic administration moderately increases the size of medium-size bronchioles and therefore reduces airway resistance. Abuse is common amongst long-distance cyclists, as the transfer of oxygen to the circulation is limited when exercising, so athletes undergo oxygen desaturation.
Beta agonists also change the distribution of fast and slow muscle fibres, increasing fast fibres and so power. Beta agonists induce transcription factors associated with muscle fibre type. They therefore increase DNA transcription and RNA translation.
Studies were performed in mice. As the animal gets older, slow type I fibres increase and fast type II fibres decrease. Fast fibres were maintained in beta-2 adrenoceptor agonist treated mice compared to control mice.
MyoD is a transcription factor that regulates he MHC-IIB gene associated with fast myosin. Expression is elevated in mice treated with a beta-2 agonist.
Moreover, the muscle also takes on the biochemical phenotype of the fast muscle.
The phenotypic changes as a result of beta 2-agonist administration are paralleled by concomitant changes in cellular energy metabolism towards a faster phenotype, as ATP content in the muscle increases.
Side effects of beta-2 adrenoreceptor agonists administration include both neurological and cardiovascular effects including: tremor, headache, palpitations, tachycardia, hypertension, muscle cramps, hypokalaemia, hyperglycaemia, anxiety, agitation, sweating.
Long-term side effects include: increased risk of heart disease and stroke, kidney and liver damage, muscle weakness, anxiety and depression.
Myostatin inhibition
Myostatin inhibits myoblast proliferation and differentiation in healthy individuals, therefore inhibiting muscle growth.
Knocking out myostatin in animals increases muscle mass.
Bimagrumab (Novartis) is a human monoclonal antibody that binds to the TGF-β receptor and prevents the actions of myostatin that negatively regulates skeletal muscle growth.
The researchers put one leg of healthy volunteers in a cast for 2 weeks, which reduced muscle mass, with total muscle volume decreasing by 4%. After this time, a group was given a single injection of Bimagrumab and one of placebo.
The drug restored muscle mass to baseline volumes within 2 weeks. The muscle then continued to grow, so at the end of 12 weeks it was 4% greater than the control group, which returned to baseline. In the non-casted leg, the effect was even bigger (6% higher in Bimagrumab).
Myostatin inhibition is therefore highly anabolic.
However, there was no difference in muscle function as a result of the drug, so there was no increase in strength. This has resulted in pharmaceutical companies abandoning this approach.
The lack of increase in strength may be because extra energy has to be expended to contract the extra muscle.
As a therapeutic intervention for atrophy this is not viable. However, athletes train intensively when abusing these drugs, so the increase in mass may translate to functional gains. This led to a ban on myostatin inhibitors in and out of competition.
Fat mass was also significantly reduced in individuals who received a single injection of the drug.
In type 2 diabetes patients, over 48 weeks, the Bimagrumab-treated group showed a clear reduction in body fat mass. This may have positive metabolic effects in diabetes.
Athletes who want to go down a weight category without losing muscle mass may abuse such drugs.
