Androgens Flashcards
How is testosterone synthesised? How is to found in the body?
it is produced from cholesterol primarily by leydig cells in the testes
- uses 5 enzymes to convert from cholesterol to testosterone
testosterone is found bound to albumin and serum sex hormone binding globulin (SSBG)
What is DHT? What is it responsible for?
DHT is 5-alpha dihydrotestosterone
- it is more potent than testosterone
it is responsible for many response to testosterone in the urinary-genital
- benign prostate hyperplasia (non-cancerous enlargement of the prostate gland)
What kind of testosterone is active? What does SSBG act as? How is testosterone converted to dihydrotestosterone and estradiol?
free and loosely bound albumin fractions of testosterone are biologically active
albumin bound to serum sex hormone binding globulin (SSBG) acts as a reservoir for androgens
testosterone is converted to dihydrotestosterone by 5-alpha reductase
testosterone is converted to estradiol by aromatase
What is the mechanism of action of testosterone?
testosterone enters cells
- does not need membrane receptor or carrier as it is made of cholesterol
it is converted to dihydrotestosterone via 5-alpha reductase (more potent form)
DHT binds to androgen receptor/heat shock protein complex
- AR is partially phosphorylated and the complex disassociated upon binding allowing the HSP to go free
AR/DHT complex enter the nucleus and interacts with androgen response elements in DNA
- increases gene transcription and translation resulting in greater protein synthesis
How does testosterone affect foetus, pre-pubertal children and boys during puberty?
foetus
- promotes development of male reproductive tract and external genitalia
pre-pubertal children
- prematurely closes the epiphyses of the long bones
= will stunt growth
children
- promotes development of primary sexual characteristics
= enlargement of penis, scrotum and testes
- promotes development of secondary sexual characteristics
= male body shape, muscle growth, facial/pubic hair, deeper pitch of voice
How does testosterone affect adults?
adults
- promotes retention of salt and water
- thickening and darkening of skin
- sebaceous glands become more active
- body weight and muscle mass will increase
- feeling of well being, increased libido and physical vigour
- paradoxically exogenous testosterone inhibits spermatogenesis
What causes androgen deficiency?
What causes hypothalamic pituitary disorders?
What causes ambiguous genitalia, delayed puberty and infertility?
androgen deficiency is caused by testicular disorders
hypothalamic pituitary disorders
- high LH and low testosterone levels
ambiguous genitalia, delayed puberty and infertility
- low LH and low testosterone levels
What is androgen replacement therapy (ART) used to treat?
male hypogonadism
- treated in order to develop and maintain sex characteristics
= typically causes underdevelopment
andropause
= caused by decline in levels of testosterone which occurs in older age
What are the signs and symptoms of adult male hypogonadism? How can it be diagnosed?
signs
- decreased body hair, decreased muscle mass, small prostate and testes
- gynecomastia, osteoporosis, anaemia
symptoms
- decreased libido, erectile dysfunction, infertility, fatigue, weakness, depression, irritability,
diagnostic
- normal levels of testosterone is 300-1000 ng/dl
- less than 300 ng/dl is positive hypogonadism
What are the causes of adult male hypogonadism?
autoimmune disorders
- Addison’s disease = adrenal insufficiency
- hypoparathyroidism = resulting in reduction in renal calcium absorption
genetic disorders
- klinefelter syndrome = boys have an extra X chromosome
severe infections
liver and kidney disease
hemochrombtosis = absorption of excess iron
radiation exposure
surgery on genitalia
What causes andropause? What effects does treating it have on symptoms?
progressive decline in testosterone levels
- due reduced number and activity of leydig cells
pharmacological doses can
- increase muscle mass and strength
- increase cognition and sense of well being
- increase LDL (CVD risk)
- increase prostate size and urinary symptoms (prostate cancer and BPH risk)
Why is testosterone given via i.m injections? What are the benefits of implants, capsules and patches?
testosterone is given via i.m injections as it is inactivated by the liver if given orally
implants, capsules and patches
- can improve compliance
- can have more stable levels and symptoms with effects lasting months
What are the different types of androgen therapy?
testosterone (histerone)
- oral administration leads to absorption into hepatic circulation and rapid catabolism (breakdown)
- is effective in transdermal patches
methyltestosterone (metandren) - 17 alpha alkylated testosterone
- hepatic metabolism is retarded, has reduced androgenicity and is somewhat hepatotoxic
- is taken orally
17 alpha hydroxyl group esters
- testosterone propionate
- testosterone enanthate
- testosterone undecanoate
= are given via i.m injection
= are more lipophilic than testosterone and are converted to testosterone in circulation
What are the adverse effects, contraindications and precatuions associated with androgen replacement therapy (ART)?
adverse effects - are uncommon
contraindications - prostate and breast cancer
cautions
- ART may cause urinary obstruction and unfamiliar increased libido in older men
- ART may close epiphyseal closure in pubertal boys causing short stature
- avoid i.m injections in men with bleeding disorders
- associated with androgen sensitive epilepsy, migraines and polycythaemia
How can prostate cancer be treated?
anti-gonadotrophin releasing hormone
- gonadotrophin hormone releasing hormone agonists such as gosrelin, buserelin, leuprorelin
= act by initially increasing GnRH, LH and testosterone release then acting negative feedback loop to reduce release and expression of receptors
GnRH receptor antagonist
- degarelix
= competitively inhibits GnRH receptors in the pituitary gland, preventing the release of LH
anti-androgen
- cyproterone acetate, flutamide
= blocks binding of testosterone and DHT to androgen receptors
