Androgens and Anabolic Steroids Flashcards
What are the actions of testosterone, grouped by location of action?
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
What cells produce testosterone in the testes?
Leydig cells produce testosterone in response to LH.
Where is testosterone produced in the body?
95% testicular, 5% adrenal
What does LH and FSH stimulate in men?
LH stimulates testosterone synthesis by Leydig cells.
FSH AND testosterone act on Sertioli cells in seminiferous tubules to:
- Support spermatogenesis
- Secrete androgen binding protein
What are the androgenic and anabolic effects on testosterone?
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
When are the peaks of production of testosterone through life?
Peaks in first trimester, in neonates, and then after puberty.
What are the functions of testosterone in fetus and in puberty?
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
Describe the two enzymes involved in the metabolism of testosterone into other compounds. What do these other compounds do?
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
Where is 5α-reductase expressed?
Penis, scrotum.
NOT in testes.
Where is 5α-reductase expressed?
Penis, scrotum.
NOT in testes.
How does testosterone travel in the blood?
It is lipid soluble.
98% bound to SHBG/albumin, 2% free.
What are the two causes of androgen deficiency?
Testicular (aka. primary hypogonadism)
Hypothalamic-pituitary (aka. secondary hypogonadism)
What are three types of testicular (primary) hypogonadism?
- Chromosomal
- Cryptorchidism (one or both testes don’t descend from abdo)
- Trauma/Chemo/Radio
What is the cause of hypothalamic-pituitary (secondary) hypogonadism?
Pituitary insufficiency:
- Adenoma
- Surgery
- Trauma
What are LH levels like in primary vs secondary hypogonadism?
Primary - LH levels are high.
Secondary - LH levels are low.
How does androgen deficiency present?
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.
How is androgen deficiency treated?
Androgen replacement therapy (ART)
How is androgen replacement therapy administered?
Intramuscular injections of testosterone esters every 2 - 3 weeks.
Testosterone has high first pass metabolism - testosterone esters are bioconverted into testosterone .
Adverse effects of ART?
- 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
What are contraindications for ART?
Prostate cancer and breast cancer in men
- Driven by androgen receptor thus can’t give more androgens.
What is the difference between misuse and abuse of ART?
Misuse = prescription with no good medical indication.
Abuse = obtained without legal prescription in absence of medical indication.
What are two examples of misguided prescribing of ART, and the consequence of using AAS in their case?
- ED
Results in increased libido with no change in erectile capacity
- Male infertility
Further suppression of spermatogenesis
When is ART the unquestioned method of therapy?
In testicular or hypothalamic-pituitary disorders with severe androgen deficiency
What are two examples of partial androgen deficiency where ART may help?
- Boys experiencing delayed onset of puberty
ART may stimulate puberty and growth
- Older men experiencing androgen deficiency (andropause)
ART may prevent bone and muscle loss, increase vigour and libido
Why is andropause difficult to diagnose?
Androgen levels steadily decline as we age. Hard to tell if ART will help.
Why do people abuse AAS?
Supra-physiological doses of AAS allow users to greatly increase muscle mass/strength and repair micro-tears in soft tissue.
What are ‘designer steroids’
Aims to maximise anabolic effects of AAS, trying not to be converted into estradiol or DHT.
However, none are completely anabolic-effect selective.
Side effects of AAS abuse?
- Masculinisation of women
- Acne
- Testicular atrophy and reduction in spermatogenesis
- Premature epiphyseal closure
- Mood swings, aggression
- Dyslipidaemia and HTN
What are SARMs?
Give an example.
Selective androgen receptor modulators
Synthetic molecules that stimulate anabolic effects without the androgenic side effects.
Example = ligandrol
