Androgens and Anabolic Steroids

Question 1

Where are endogenous androgens produced and how much do men produce daily?

Answer 1

Endogenous androgens are produced by the leydig cells of the testes and the zona reticularis of the adrenal glands.

Men produce 6 - 8 mg daily (20x that of women)

Women also produce adrenal testosteron

Question 2

What does testosterone do?

Answer 2

Androgenic effects:

Foetal male sex organ development

Pubertal maturation of male sex organs

Maintenance of male characteristics

Spermatogenesis

Anabolic effects:

Increase protein synthesis

Increase muscle and bone mass

Question 3

When does testosterone production in males peak?

Answer 3

In the 1st trimester, then in neonates, then after puberty

Question 4

What does testosterone do in foetus and neonate?

Answer 4

Important for development of male reproductive tract:

Forms the wolffian ducts which form epididymis/vas/seminal vesicles

Question 5

What does testosterone do during puberty?

Answer 5

Primary sex characteristics - Penis, scrotum, and testis enlargement.

Secondary sex characteristics enlargement - body shape, facial/pubic hair, deeper voice

Spermatogenesis (300k/min)

Question 6

How is testosterone production controlled at puberty?

Answer 6

GnRH -> ALP -> LH and FSH

LH -> Leydig cells produce testosterone

FSH -> Sertoli cells in seminiferous tubules support spermatogenesis and produce androgen binding protein.

Secreted T binds to ABP

Intra-testicular T levels&raquo_space; circulating levels (25 - 100x)

T binds AR in sertoli cells to regulate spermatogenesis

Circulating T inhibits both GnRH and gonadotropic production - negative feedback loop.

Question 7

Which tissues express 5alphareductase?

Answer 7

Penis, scrotum, and prostate

NOT THE TESTIS

Question 8

What does DHT do?

Answer 8

Regulates:

External genitalia maturation

Penis loses AR expression after puberty

Prostate gland hyperplasia

Question 9

What fate does testosterone have besides becoming DHT?

Answer 9

It can be converted to 17beta estradiol in the testes, prostate and bone.

This is needed for production of healthy, motile sperm and for healthy bones (osteopaenia)

Question 10

Where in the genome is the androgen receptor gene located?

Answer 10

AR gene - X chromosome

Question 11

Where is the AR expressed?

Answer 11

Reproductive tissue

Skeletal muscle

Brain, kidney, etc

Question 12

Where in the cell is the AR expressed? What is the result?

Answer 12

Nuclear receptor:

Androgen binding -> AR homodimerisation + Nuclear translocation

AR binds specific DNA motifs (AREs) in promoter regions of androgen responsive genes -> transcription

Question 13

Which androgen is more potent T or DHT?

Answer 13

DHT is 5x more potent.

Question 14

How do testosterone levels vary?

Answer 14

Time of day

Lipid soluble and free testosterone is only ~2% of what is in the blood but it is the only part that is available for binding.

Affected by:

Season

Recent meal

Taking care of a baby

Question 15

How is an androgen deficiency measured?

Answer 15

Confirmed by hormonal assays

Diurnal variation in testosterone levels - increased testosterone nocturnally is expected.

Question 16

What causes androgen deficiency?

Answer 16

Testicular deficiency due to primary hypogonadism. This can be seen if there is high LH but low T. (Chromosomal such as XXY, XX males, cryptorchidism, trauma, chemotherapy, etc)

Hypothalamus-pituitary (secondary hypogonadism: This is seen by low LH and T levels. (Caused by pituitary insufficiency due to adenoma, surgery, or trauma, or it can be caused by hypothalamic problems like kallman syndrome and prader-willi syndrome)

Question 17

How is androgen deficiency treated?

Answer 17

Androgen replacement therapy for life to restore tissue androgen levels.

Question 18

What are the consequences of androgen deficiency?

Answer 18

Ambiguous genitalia, delayed puberty, and infertility

Decreased libido, mood, and vitality.

Drop in bone density, haematocrit, muscle mass, cognition

Metabolic syndrome risk.

Question 19

How is testosterone replacement therapy administered?

Answer 19

IM injections (Tesosterone Enanthante)

Newer formulations avoid first pass metabolism such as s.c. implants and transdermal gels and patches.

Question 20

What are the adverse effects of TRT?

Answer 20

Gynaecomastia

Urinary obstruction (Dont use in older men)

Question 21

What are the contraindications of TRT?

Answer 21

Prostate cancer

Breast cancer

Puberty avoid giving to prevent early epiphyseal closure

Old men (Urinary obstruction and libido)

Androgen-sensitive epilepsy, mygraine, polycythaemia

Bleeding disorders

“Bystander effects” - testosterone gels can affect children with skin to skin contact.

Question 22

When to prescribe ART?

Answer 22

Severe androgen deficiency. (ART is questioned)

Partial androgen deficiency (Stimulating onset of puberty and growth, preventing bone loss, increased vigour and libido, reversing catabolic state)

Question 23

What are the symptoms of low androgen levels?

Answer 23

Decrease in muscle mass and strength

Decreased bone mass -> Osteoporosis

Increased central body fat

Decreased libido

Erectile dysfunction (more commonly secondary to vascular dysfunction)

Question 24

What effects has modern research shown TRT to have on male ageing?

Answer 24

Improved sexual function

No improvements in physical function, vitality, cognition, and bone health.

Increased coronary artery plaque formation.

Question 25

What are the adverse effects of misused AAS?

Answer 25

Masculinisation

Acne

Testicular atrophy

Premature epiphyseal closure

Infertility

Mood disturbance, aggression and cognition

Dyslipidaemia and hypertension

Polycythaemia

Hepatitis and hepatic tumours

Question 26

What are the cognitive effects of AAS?

Answer 26

Aggression, loss of impulse control, and roid rage

Impairs decision making

Overconfidence

Question 27

What are the CVS effects of AAS?

Answer 27

Lowers HDL cholesterol and increased markers of inflammation and inflammation.