Androgens and Anabolic Steroids

Question 1

What are the actions of testosterone, grouped by location of action?

Answer 1

Locally

• Acts on Sertoli cells to induce gametogenesis

Peripherally

• Converted to DHT by 5α-reductase to act on secondary sex organs and other tissues that express androgen receptors

Negative Feedback

• ACts on GnRH and FSH and LH to reduce levels

Question 2

What cells produce testosterone in the testes?

Answer 2

Leydig cells produce testosterone in response to LH.

Question 3

Where is testosterone produced in the body?

Answer 3

95% testicular, 5% adrenal

Question 4

What does LH and FSH stimulate in men?

Answer 4

LH stimulates testosterone synthesis by Leydig cells.

FSH AND testosterone act on Sertioli cells in seminiferous tubules to:

• Support spermatogenesis
• Secrete androgen binding protein

Question 5

What are the androgenic and anabolic effects on testosterone?

Answer 5

Androgenic:

• Male sex organ development
• Pubertal maturation of male sex organs
• Maintenance of male characteristics
• Spermatogenesis

Anabolic: Growth stimulating:

• Increased protein synthesis
• Increased muscle/bone mass

Question 6

When are the peaks of production of testosterone through life?

Answer 6

Peaks in first trimester, in neonates, and then after puberty.

Question 7

What are the functions of testosterone in fetus and in puberty?

Answer 7

Fetus/neonate:

• Development of male reproductive truct
• Wolffian ducts → Epididymis/vas deferens/seminal vesicles

Puberty:

• Primary sex characteristics (penis, scrotum and testicular enlargement)
• Secondary sex characteristics (deeper voice, facial and body hair)
• Spermatogenesis

Question 8

Describe the two enzymes involved in the metabolism of testosterone into other compounds. What do these other compounds do?

Answer 8

5α-reductase - T → DHT

• 5x more potent than T
• Regulates maturation of external genitali and drives prostate hyperplasia

Aromatase - T → 17β-estradiol

• Healthy, motile sperm
• Healthy bone

Question 9

Where is 5α-reductase expressed?

Answer 9

Penis, scrotum.

NOT in testes.

Question 10

Where is 5α-reductase expressed?

Answer 10

Penis, scrotum.

NOT in testes.

Question 11

How does testosterone travel in the blood?

Answer 11

It is lipid soluble.

98% bound to SHBG/albumin, 2% free.

Question 12

What are the two causes of androgen deficiency?

Answer 12

Testicular (aka. primary hypogonadism)

Hypothalamic-pituitary (aka. secondary hypogonadism)

Question 13

What are three types of testicular (primary) hypogonadism?

Answer 13

• Chromosomal
• Cryptorchidism (one or both testes don’t descend from abdo)
• Trauma/Chemo/Radio

Question 14

What is the cause of hypothalamic-pituitary (secondary) hypogonadism?

Answer 14

Pituitary insufficiency:

• Adenoma
• Surgery
• Trauma

Question 15

What are LH levels like in primary vs secondary hypogonadism?

Answer 15

Primary - LH levels are high.

Secondary - LH levels are low.

Question 16

How does androgen deficiency present?

Answer 16

Does not decrease life expectancy, but is associated with significant morbidity:

• Decreased libido, mood and vitality
• Delayed puberty and infertility
• Decreased bone density, muscle mass and cognitiion.

Question 17

How is androgen deficiency treated?

Answer 17

Androgen replacement therapy (ART)

Question 18

How is androgen replacement therapy administered?

Answer 18

Intramuscular injections of testosterone esters every 2 - 3 weeks.

Testosterone has high first pass metabolism - testosterone esters are bioconverted into testosterone .

Question 19

Adverse effects of ART?

Answer 19

• Serum levels aren’t normalised with ART - mood swings, libido loss
• Gynaecomastia
• Increased prostatic hypertrophy in older men
• Early epiphyseal closure if used in puberty

Question 20

What are contraindications for ART?

Answer 20

Prostate cancer and breast cancer in men

• Driven by androgen receptor thus can’t give more androgens.

Question 21

What is the difference between misuse and abuse of ART?

Answer 21

Misuse = prescription with no good medical indication.

Abuse = obtained without legal prescription in absence of medical indication.

Question 22

What are two examples of misguided prescribing of ART, and the consequence of using AAS in their case?

Answer 22

1. ED

Results in increased libido with no change in erectile capacity

2. Male infertility

Further suppression of spermatogenesis

Question 23

When is ART the unquestioned method of therapy?

Answer 23

In testicular or hypothalamic-pituitary disorders with severe androgen deficiency

Question 24

What are two examples of partial androgen deficiency where ART may help?

Answer 24

1. Boys experiencing delayed onset of puberty

ART may stimulate puberty and growth

2. Older men experiencing androgen deficiency (andropause)

ART may prevent bone and muscle loss, increase vigour and libido

Question 25

Why is andropause difficult to diagnose?

Answer 25

Androgen levels steadily decline as we age. Hard to tell if ART will help.

Question 26

Why do people abuse AAS?

Answer 26

Supra-physiological doses of AAS allow users to greatly increase muscle mass/strength and repair micro-tears in soft tissue.

Question 27

What are ‘designer steroids’

Answer 27

Aims to maximise anabolic effects of AAS, trying not to be converted into estradiol or DHT.

However, none are completely anabolic-effect selective.

Question 28

Side effects of AAS abuse?

Answer 28

1. Masculinisation of women
2. Acne
3. Testicular atrophy and reduction in spermatogenesis
4. Premature epiphyseal closure
5. Mood swings, aggression
6. Dyslipidaemia and HTN

Question 29

What are SARMs?

Give an example.

Answer 29

Selective androgen receptor modulators

Synthetic molecules that stimulate anabolic effects without the androgenic side effects.

Example = ligandrol