Exam 1 - Performance Enhancing Drugs

Question 1

The effects of anabolic steroids are generally characterized by —-, while the effects of androgenic steroids are characterized by ——.

Answer 1

anabolic - strength and endurance
androgenic - masculinization (libido, acne, facial hair, growth of prostate, and deepening of voice)

Question 2

Describe the setup and results of the exogenous testosterone muscle size/strength study.

Answer 2

4 groups - placebo and testosterone for both an exercise and no exercise group

testosterone increases muscle area and strength with or without exercise

combination of both testosterone and exercise gives greatest increase in muscle area and strength

Question 3

People taking a higher dose of exogenous testosterone will have —– sperm concentrations.

Answer 3

lower

Question 4

What is the basic steroid molecular structure?

Answer 4

A B C and D rings, with all being 6 carbon except for D, which is a 5 carbon ring

Carbons numbered 1-17, with 17 at the top of the D ring

Question 5

Describe the structure and groups of a testosterone molecule

Answer 5

testosterone has A B C and D rings

Carbons 18 and 19 are methyl groups off of carbon 10 and 13

There is an OH and H on carbon 17

There is a =O on carbon 3

There is a double bond between carbon 4 and 5 of ring A

Question 6

What kinds of structural modifications to testosterone can be used for synthetic steroids?

Answer 6

modify A and B rings to maximize anabolic activity and minimize androgenic activity

modify 17 carbon to determine oral or depot delivery
- 17 a-alkyl group confers oral activity by preventing deactivation by the gut or liver (first pass metabolism)
- esterification of 17 carbon confers activity for depot delivery (because it takes time for the ester group to be cleaved off and make the active form)

Question 7

What are some routes of steroid drug administration?

Answer 7

oral (subject to first pass effect)
injection (subcutaneous or intramuscular)
pellet implant
transdermal (gel or patch)
sublingual troche
nasal spray
intra-vaginal
suppositories

Question 8

What is the first pass effect/first pass metabolism?

Answer 8

drug metabolism where the concentration of the drug is greatly reduced before it reaches the systemic circulation

Question 9

What are the 4 potential systems involved in first-pass metabolism?

Answer 9

gut wall enzymes
gastrointestinal lumen enzymes
bacterial enzymes
hepatic enzymes

Question 10

How is a oral drug carried through the digestive system (vessels), and where does the concentration decrease?

Answer 10

enters the stomach at 100%, gut wall/gastrointestinal lumen/bacterial enzymes reduce to 70% which enters the hepatic portal vein, carries to liver where hepatic enzymes reduce it to 15%, and the hepatic vein carries that 15% into the systemic circulation

Question 11

What vessels enter and exit the liver?

Answer 11

hepatic portal vein enters the liver from the digestive tract

hepatic vein enters the systemic circulation from the liver

Question 12

Non-oral routes of administration are good because they…

Answer 12

Avoid first-pass metabolism and allow drugs to be absorbed directly into the systemic circulation

Question 13

What structural modification happens to the testosterone molecule when it is converted to DHT?

Answer 13

The double bond is broken and a hydrogen is added on instead (there is no double bond between carbon 4 and 5)

Question 14

Does testosterone or DHT have a greater affinity for androgen receptors?

Answer 14

DHT

Question 15

How is the structure of nandrolone different from testosterone? What effect does this cause?

Answer 15

No 19 carbon (methyl group) on carbon 10

Greater affinity for androgen receptors than testosterone (more anabolic response)

Question 16

How is the structure of 5a-dehydro-19-nortestosterone different from DHT? What effects does this cause?

Answer 16

No 19 carbon (methyl group) on carbon 10

Lesser affinity for androgen receptors than DHT, so decreased androgenic response

Question 17

Is myotrophic similar to anabolic or androgenic?

Answer 17

Anabolic

Question 18

In the myotrophic-androgenic index study, what were they measuring? What were each of those measures supposed to indicate?

Answer 18

Levator ani muscle - anabolic/myotrophic target
Prostate gland - androgenic target

Question 19

Describe the Hershberger Bioassay

Answer 19

Immature, castrated male rats
Given a steroid of interest or a reference steroid via injection or oral gavage
Dosed every 24 h for 10 days
Animals sacrificed and levator ani/prostate are measured

Question 20

How is the myotrophic and androgenic activity calculated?

Answer 20

Myotrophic activity = increase in levator ani weight with steroid of interest / increase in levator ani weight with control steroid

Androgenic activity = increase in prostate weight with steroid of interest / increase in prostate weight with control steroid

Question 21

How is index value calculated?

Answer 21

Myotrophic activity / androgenic activity

Question 22

What does a high index value indicate?

Answer 22

Higher anabolic affects with lower androgenic effects (which is preferred)

Question 23

Can anabolic effects ever be completely separated from androgenic effects?

Answer 23

No, but some synthetic steroids present large index values with a high dissociation between the two

Question 24

What are adverse effects on bone, breast, cardiovascular, and nervous systems from anabolic androgenic steroid use?

Answer 24

Bone - premature closure of epiphysis in children
Breast - T converted to E cause gynecomastia in males
Cardiovascular - increase risk for myocardial infarction, stroke, raised LDL and lowered HDL
Central Nervous System - increased aggression

Question 25

What are adverse effects on hair, liver, skin, and vocal cords from anabolic androgenic steroid use?

Answer 25

Hair - hirsutism in women and accelerated male pattern baldness in men (excess DHT damages the hair follicle)
Liver - impaired function/hepatotoxicity
Skin - cystic acne
Vocal cords - deepening of voice in females

Question 26

What are the adverse effects on the reproductive system from anabolic androgenic steroid use?

Answer 26

Suppression of gonadal steroidogenesis
Testicular atrophy
Abnormal prostate growth
Amenorrhea

Question 27

What is an epimer?

Answer 27

One of two molecules that differ only in the spatial arrangement of the H and OH around a single carbon atom

Question 28

What is epitestosterone? What is the T/E ratio, and what happens when someone takes exogenous testosterone?

Answer 28

An epimer of testosterone with no anabolic activity

T/E ratio is normally about 1:1 but urinary T/E ratio increases with exogenous T

Question 29

How does the World Anti-Doping Agency define what is an adverse difference in T/E ratio vs. natural variation?

Answer 29

T/E ratio greater than 4 indicates doping

Question 30

What can be done to fake a “normal” T/E ratio?

Answer 30

Epitestosterone propionate - balances the T/E ratio
“The Cream” - transdermal preparation containing both testosterone and epitestosterone

Question 31

How can dietary supplements be used as steroids?
What is a common example? Describe the study that analyzed this administration.

Answer 31

Some dietary supplements contain anabolic steroid pro hormones, which are designed to be converted by the body to anabolic steroids
Ex: Androstenedione is a prohormone for testosterone. In the study by Leder, dosages or oral androstenedione increased the serum estrogen (128%) even more than it increased the serum testosterone (only 34%), and estrogen can lead to feminizing effects