Androgens and Anabolic Steroids Flashcards
Where are endogenous androgens produced and how much do men produce daily?
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
What does testosterone do?
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
When does testosterone production in males peak?
In the 1st trimester, then in neonates, then after puberty
What does testosterone do in foetus and neonate?
Important for development of male reproductive tract:
Forms the wolffian ducts which form epididymis/vas/seminal vesicles
What does testosterone do during puberty?
Primary sex characteristics - Penis, scrotum, and testis enlargement.
Secondary sex characteristics enlargement - body shape, facial/pubic hair, deeper voice
Spermatogenesis (300k/min)
How is testosterone production controlled at puberty?
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»_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.
Which tissues express 5alphareductase?
Penis, scrotum, and prostate
NOT THE TESTIS
What does DHT do?
Regulates:
External genitalia maturation
Penis loses AR expression after puberty
Prostate gland hyperplasia
What fate does testosterone have besides becoming DHT?
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)
Where in the genome is the androgen receptor gene located?
AR gene - X chromosome
Where is the AR expressed?
Reproductive tissue
Skeletal muscle
Brain, kidney, etc
Where in the cell is the AR expressed? What is the result?
Nuclear receptor:
Androgen binding -> AR homodimerisation + Nuclear translocation
AR binds specific DNA motifs (AREs) in promoter regions of androgen responsive genes -> transcription
Which androgen is more potent T or DHT?
DHT is 5x more potent.
How do testosterone levels vary?
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
How is an androgen deficiency measured?
Confirmed by hormonal assays
Diurnal variation in testosterone levels - increased testosterone nocturnally is expected.
What causes androgen deficiency?
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)
How is androgen deficiency treated?
Androgen replacement therapy for life to restore tissue androgen levels.
What are the consequences of androgen deficiency?
Ambiguous genitalia, delayed puberty, and infertility
Decreased libido, mood, and vitality.
Drop in bone density, haematocrit, muscle mass, cognition
Metabolic syndrome risk.
How is testosterone replacement therapy administered?
IM injections (Tesosterone Enanthante)
Newer formulations avoid first pass metabolism such as s.c. implants and transdermal gels and patches.
What are the adverse effects of TRT?
Gynaecomastia
Urinary obstruction (Dont use in older men)
What are the contraindications of TRT?
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.
When to prescribe ART?
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)
What are the symptoms of low androgen levels?
Decrease in muscle mass and strength
Decreased bone mass -> Osteoporosis
Increased central body fat
Decreased libido
Erectile dysfunction (more commonly secondary to vascular dysfunction)
What effects has modern research shown TRT to have on male ageing?
Improved sexual function
No improvements in physical function, vitality, cognition, and bone health.
Increased coronary artery plaque formation.
