L15 - Endocrinology of ageing COPY Flashcards
AGE AND NUTRITIONAL STATUS/INSULIN
i) from what age does weight increase? between what ages does it plateau?
ii) from mid 30s what % decrease in lean body mass is seen?
iii) with increasing age - what trends are seen in total energy and protein intake?
iv) how does insulin resistance and peripheral glucose uptake change with age?
v) how does the prevalence of metabolic syndrome change with age?
i) increases from 30 and plateus between 50-70
ii) decrease of 6-8% in lean body mass from 30s
iii) with increasing age - see decrease in total energy and protein intake
iv) with age - insulin resistance increases and peripheral glucose uptake decreases
v) increase of prevalence of metabolic syndrome with increasing age
METABOLIC SYNDROME
i) what is it defined as?
ii) name four things it can be associated with
iii) what is the underlying pathological mechanism?
iv) what group of individuals is metabolic syndrome most prevalent in?
i) constellation of closely associated CV risk factors
ii) hypertension, dyslipidaemia, visceral obesity and hyperglycaemia
iii) insulin resistance is the underlying pathol mechanism
iv) most prevalent in the elderly
MENOPAUSE
i) what is the menopause?
ii) what oestrogen levels are seen a) pre menopausal and b) post menopausal?
iii) how are levels of E2, LH and FSH affected post menopausal?
iv) give two symptoms of the menopause and what is the median duration of these symptoms?
v) what is the average age of menopause? + or - how many years?
vi) name three things that a woman is at increased risk of post menopause
i) ovarian failure
ii) pre menopause oestrogen levels are cycling
- post menopause oestrogen levels are at a very low constant level
iii) see decreased E2 and increased LH and FSH post meno
iv) hot flushes, night sweats (vasomotor symptoms)
- median duration of symptoms is 7 years
v) avg age of menopause is 50 +- 2 years
vi) post meno = increased risk of osteoporosis, CHD and sexual dysfunction
POST MENOPAUSAL HRT
i) what does the HRT consist of?
ii) what did initial observations show?
iii) what did subsequent RCTs show? (2)
iv) name three things that the risk benefit ratio depends on?
v) which group of woman are at greater risk (how old and duration of years post meno)
i) oestrogen and progesterone
ii) initially saw benefits
iii) later RCTs showed no benefit and increased risks
iv) risk:benetfit depends on other risk factors, age of the woman, duration of HRT use and type of HRT used
v) women who are >60yrs and have been on HRT for >10 years post meno
BENEFITS/RISK OF POST MENO HRT
i) give two benefits of HRT - how long do these benefits last?
ii) what vascular complication is patient on HRT more at risk of?
iii) name two cancer women on HRT are more at risk of? name one thing that even further increases risk of each
iv) what used to be the goal of treatment? what is it now?
i) reduction of menopausal symptoms and decreased osteoporosis/fracture risk
- reduced risks only for duration of treatment
ii) more at risk of venous thrombo embolism
iii) more at risk of breast and endometrial cancer
- inc risk of breast if HRT >5yrs
- inc risk endometrial if only oestrogen (E2) is used
iv) goal used to be replacement to prevents disorders assoc with post meno oestrogen deficiency eg osteoporosis
- goal now is treatment of menopausal symptoms
MALE GONADAL AXIS
i) how does testosterone change with age? is the gradual or sudden?
ii) at the age of 75 what proportion of a 25yr olds mean testosterone does a man have?
iii) is there good evidence for association between libido/erec dysfunc and testos concs?
iv) is there a wide or narrow range of testosterone levels in healthy men?
i) testosterone gradually decreases with age
ii) at 75 a man has 2/3 of testos of a man at 25 yrs
iii) no assoc proven between libido and testosterone levels
iv) there are a wide range of testos levels in healthy men
AGE AND MALE GONADAL AXIS
i) name three features of clinical hypogonadism
ii) what effects are seen on sexual function when testosterone treatment is given to older men?
iii) what is the main underlying cause of erectile dysfunc in older men?
iv) what is the evidence that testos improves physical/cognitive func, mood and QOL?
v) name three potential risks of testos treatment in older men
vi) name two effects of treatment on bones
vii) how does testos treatment impact on lean body mass, fat mass, muscle strength?
i) decreased sexual function and muscle strength and increased osteoporosis
ii) small improvements seen in sex func with testos
iii) underlying cause of erec dysfunc in older men is atherosclerotic
iv) little/no evidence of improvement
v) risks are prostate related (BPH or cancer), erythropoeisis (testos treatment increases haematocrit) and CV risk
vi) increased bone mineral density if hypogonadal and may also have effects on fracture risk
vii) increases lean body mass, decreases fat mass and increases muscle strength (with supraphysiol doses)
GH AND IGF1 AXIS
i) what pattern of GH secretion is seen in the young? how does this change in older people?
ii) how do levels of IGF1 produced in the liver in response to GH change with age?
iii) how does GH treatment affect lean body mass and fat mass? what effect is this similar to?
iv) what two things does it not have a significant change on?
v) name two potential risks of GH treatment
vi) give three side effects of GH treament
i) in young GH has pulsatile secretion and in older people this pulsatility is lost
ii) IGF1 produced by the liver decreases with age
iii) GH treatment increases lean body mass and decreases fat mass (similar to testosterone treatment)
iv) doesnt signficantly change bone mineral density or lipid levels
v) risks of GH treatment = cancer eg prostate, colon breast
- increased risk of T2DM (GH antag insulin)
vi) SEs of GH treatment - soft tissue oedema, joint pain and carpal tunnel syndrome
AGE & CORTISOL
i) how does the diurnal trough change with age?
ii) how do average levels of cortisol change with age?
iii) how does the time of peak and trough of cortisol curve change with age?
iv) what does sapolskys glucocorticoid cascade hypothesis state about how hippocampal GC and MC receptors change with age?
v) what is increased cortisol associated with in relation to cognitive function?
i) less of a trough as age increases
ii) average levels of cortisol increase with age
iii) time of peak and trough are both earlier in increasing age
iv) GC cascade hypoth says there is a decrease in GC and MC receptors in the hippocampus with age
v) increased cortisol is associated with decline in cognitive function
DHEA
i) what is it? where is it made?
ii) how do DHEA levels change with age?
iii) what pituitary hormone may it be stimulated by?
iv) which two receptors may it act on? how does this mediate adverse effects?
v) what is its relative contribution of androgenic affects in men?
vi) name four things that high DHEA conc is associated with?
vii) DHEA:? ratio has been found in cancer, inflamm disease and T2DM?
viii) is there evidence for use? is it a food supplement or a drug?
i) androgen that is made by the adrenals
ii) decreased levels with age
iii) can be stim by ACTH
iv) can act on androgen and oestrogen receptors - can have adverse effects on androgen/oestrogen sensitive tissues eg breast and prostate
v) little contrib to androgenic effects in men
vi) high DHEA can be assoc with increase qual of life, bone mineral density and decreased cog decline and CHD
vii) DHEA:cortisol
viii) little/no evidence for use - FDA approved (it is a supplement not a drug)
AGE & THYROID FUNCTION
i) how do TSH levels change with age?
ii) how does T4 change with age? how baout T4 to T3 conversion?
iii) how does T3 conc change with age?
iv) is T4 treatment beneficial in older age? give two risks
v) which group of people may be most at risk and should not have T4 treatment?
i) slight increase in TSH levels
ii) T4 doesnt change much but decreased peripheral T4 to T3 conversion with age
iii) T3 conc decreases
iv) T4 treatment isnt really beneficial
- increased risk of osteoporosis, atrial fibrillation
v) elderly with atherosclerotic coronary arteries
STARVATION/ANOREXIA - INSULIN, GLUCOSE & LEPTIN
i) how are insulin, glucose and insulin sensitivity affected in starvation?
ii) what tissue is leptin produed by? what does it therefore correlate with? what levels are therefore seen in starvation
iii) which brain area does leptin report nutritional info to?
iv) what does low leptin levels signal cause in relation to food intake and energy expenditure?
v) how do low leptin levels affect fertility? what can leptin also be a permissive factor for?
i) reduced insulin, glucose and increased insulin sensitivity
ii) leptin is produced by white adipose tissue therefore correlates with BMI and % body fat
- low levels are therefore seen in starvation
iii) leptin reports nutritional info the hypothalamus
iv) low leptin levels cause increased food intake and reduced energy expenditure
v) low leptin = reduced fertility
- leptin is also a permissive factor for puberty
STARVATION/ANOREXIA - OES AND TESTOSTERONE
i) what LH, FSH, oes and testos levels are seen in starvation?
ii) what type of amenorrhoea may be seen?
iii) what condition is the individual at risk of and may be given HRT and COCP to treat?
i) reduced levels
ii) hypothalamic amenorrhoea - the ovaries are working but the hypothalamus does not sense enough body fat to allow menstruation
iii) risk of osteoporosis
METABOLISM AND REPRODUCTION
i) what eating habit and body weight is seen in an ob ob mouse? (leptin deficient)
ii) what levels of gonadotrophins, dev of sexual organs, sexual maturity and fertility is seen in ob ob mouse?
iii) what happens when ob mouse is given leptin? (5)
iv) what does this demonstrate?
i) eat lots and obese
ii) low gonadotrophins, reduced dev of sexual organs, sexual maturity and not fertile
iii) give leptin = lose weight and restore reduced levels
iv) demonstrates link between metab and reproductive systems
KISSPEPTIN
i) what effect does it have on GnRH?
ii) where does it sit in the reproductive axis in the hypothalamus?
iii) which hormone are KISS1 neurons highly response to? what is this implicated in?
iv) which hormone mediates KISS influences on the reproductive system? what is this effect?
v) name two nuclei involved in kisspeptin system
i) influences pulsatile secretion (causes its secretion)
ii) at the top (apex)
iii) kisspeptin is highly responsive to oestrogen
- implicated in pos and neg feedback of sex steroids on GnRH
iv) leptin mediates kisspeptin influence on the reprod system = permissive effect
v) arcuate and periventricular nucleus
