Performance Enhancers

Question 0

What are steroids

Answer 0

 naturally occurring steroids are substances involved in growth and maintenance of body
 steroids have both
 androgenic effects (promo&on of male sexual
characteris&cs)
 anabolic effects (increase muscle mass, increase
protein synthesis, redistribu&on of body fat, increase
calcium deposits in bone)
 but users only want anabolic effect (nearly
impossible)

Question 1

What are performance enhances

Answer 1

 they are the major performance-enhancing drugs
 based on testosterone - includes testosterone but mostly synthe&c deriva&ves
 originally used to allow malnourished pa&ents to gain weight and muscle
Now a lifestyle drug

Question 2

What are the changes to testosterone that make it more efficacious

Answer 2

 removal of the 19-methyl group increases anabolic effects esp. on muscle, greatly reduces androgenic effects
 adding ring structure to C2 and C3 increases anabolic effect
 addi&on of methyl groups at C17 increases anabolic effects and greatly reduces liver metabolism so can be taken orally – also not converted to 17β-estradiol

Question 3

How are anabolic steroids detected

Answer 3

 look for ra&os between different steroids
 can examine ra&o between testosterone and epitestosterone (naturally occurring, stable low levels)
 Floyd Landis had 11:1, normal is 1:1, cutoff is 4:1

Question 4

What are designer steroids

Answer 4

 designer steroids are a big issue now
 modifica&on of exis&ng steroids by illicit drug labs
 advantage - most drug tes&ng only iden&fies known drugs
 but no safety tes&ng, no one really knows what they do

Question 5

Explain the mechanism of steroids

Answer 5

 anabolic steroids bind to the androgen receptor
 But incredibly high concentra&ons of androgens results in them binding to other receptors as well, eg estrogen receptors and to trigger other signaling pathways
 complex enters nucleus and binds to specific region of DNA
 this ac&vates certain genes
 they make messenger (m) RNA
 mRNA used to make new proteins - eg for muscle mass
 steroids also steer stem cells into muscle cells and prevent them forming fat cells

Question 6

What are some of the effects if steroids in men

Answer 6

 hypogonadism - testes react by producing less of their own testosterone
 tes&cles shrink, sperm count in lowered
 Infec&on from injec&ons including HIV
 Male breasts enlarge (gynecomas&a) because testosterone is the precursor to estradiol (an estrogen) - mediated by aromatase enzyme

Question 7

What is the function of aromatase inhibitors

Answer 7

 Users now take aromatase inhibitors to minimize gynecomastia : blocks conversion to estrogens

Question 8

What are the effects f steroids on women

Answer 8

in woman - masculiniza&on, facial hair, balding, decreased breast size, loss of period

Question 9

Explain how steroids produce acne fulminaris

Answer 9

severe acne - can leave permanent scars
 steroids enlarge sebaceous glands
 increase sebum produc&on
 increase cell growth in hair follicles
 increase Propionibacterium acnes bacteria popula&on

Question 10

What is the function of human chorionic gonadotropin

Answer 10

 some users take human chorionic gonadotropin
 this hormone s&mulates testes to secrete their own
testosterone
 repeated treatments ocen have opposite effects
 side effects include headache, mood swings, depression , fluid reten&on

Question 11

What are the effects steroids on the liver

Answer 11

 the liver metabolizes steroids
 increased risk of liver tumors
 benign blood-filled cysts that can cause liver failure or bleeding out
 usually reversible upon cessa&on

Question 12

What are some steroid effects on other organs

Answer 12

 good evidence for increased blood pressure, high cholesterol and heart abnormali&es
 many steroid abusers die from cardiac issues - heart aeack, stroke
 steroids will increase muscle mass of heart but not blood vessels needed to deliver oxygen to it
 strong causa&ve link between chronic use and cardiac issues not scien&fically proven in humans

Question 13

Explain cardiovascular damage with steroids

Answer 13

 increase in LDL:HDL ra&o
 increased platelet aggrega&on - blood clots
 immune cells s&ck to vessel walls increasing inflamma&on
 inhibits synthesis of nitric oxide (a vasodilator)

Question 14

What is roid rage

Answer 14

 “Roid rage” is a term used to describe aggression and anger/
rage in users
 proven in several studies - not a myth
 psychosis and depression also
 several studies have found increased suicides in users
 more common in dependent users (63% vs 16% non dependent)
 steroids have been shown to modulate the ac&vity of GABA-A and NMDA receptors - this may be the link between steroids and mood issues
 these receptors have binding sites for steroids and may be normally modulated by “neurosteroids” produced in brain

Question 15

What is the function of the anterior hypothalamus

Answer 15

 the anterior hypothalamus (AH) seems to be the centre of aggression
 s&mula&on of D2 receptors in the AH will result in aggression and violence in animal models
 moderate doses of anabolic steroids in adolescence increase D2 receptor expression in the AH

Question 16

What are the effects of serotonin vs arginine vasopressin

Answer 16

 arginine vasopressin (AVP) is excitatory and poten&ates aggression while serotonin is inhibitory and decreases aggression
 exposure to anabolic steroids increases AVP effects and decreases serotonin effects

Question 17

What does chronic naldrone exposure do

Answer 17

 chronic nandrolone exposure increases aggression in mice
 decreases the mRNA levels for 5HT receptors in several brain regions including pre-frontal cortex, hypothalamus, hippocampus, amygdala

Question 18

What are the implications of steroid on brain derived neurotrophic factor?

Answer 18

 abuse linked to brain-derived neurotrophic factor (BDNF) decrease in rats
 BDNF can s&mulate neuronal growth in hippocampus
 effect reversed with chlorimipramine, an an&depressant
 in rats, correlates with depressed behaviour

Question 19

What are some developmental issues associated with steroid use

Answer 19

  steroid use during adolescence can alter development
  overall height is diminished because the growth of
long bones (eg femur) is inhibited
  growth plates at the end of growing long bones are composed of car&lage-producing cells
  in presence of anabolic steroids - growth plates prematurely converted into bone - premature end of growth phase
  in girls, puberty delayed - can remain looking like a prepubescent girl

Question 20

Does steroids increase muscle mass?

Answer 20

Originally studies showed only small increases in muscle growth and strength in laboratory
 but - these doses were small compared to what happens in the real world - and records from countries that dope show they work
 Currently good evidence for significant weight gain that seems to be related to increased muscle mass
 E.g. in carefully controlled studies, a 10 week course of steroids led to 2 – 5 kg increases in weight that were linked to muscle gain
 Linked to increase in baseline strength tests of 5 – 20% depending on dose and increased performance in sports

Question 21

What are the implications with steroid dependence

Answer 21

  many users show typical signs
  unable to control or decrease use
  take more steroids than intended
  develop tolerance to some effects
  take them to avoid withdrawal
  addi&onally, shown that when steroids modulate GABA-A receptors there is an increased firing rate of dopaminergic neurons in the mesolimbic pathway

Question 22

Are steroids reinforcing?

Answer 22

 animals will readily self-administer
 hamsters will actually overdose on them
and die acer a “binge”
 overdoses look suspiciously like opiate
overdoses
 can even be prevented with naloxone - does this mean they are ac&va&ng opioid receptors?
 of steroid users that use other drugs, opioids are most common - shared mechanism?