L12 - Endocrinology of Ageing Flashcards
Associations and Causations of hypogonadism / growth hormone deficiency / ageing
-fat mass, visceral fat
-Sarcopaenia
¯decr Bone mineral density
¯decr QOL / mood
-risk cardiovascular disease
‘Phenotypes’ are: Non-specific, High prevalence
Ageing: nutritional status
how does weight change (+from when)
lean body mass change
(+from when)
how does the diet change
WEIGHT
↑ from mid-30s
→ 50 – 70
LEAN BODY MASS
↓ 6-8% / decade from mid-30s
DIET
Trend towards ↓ intake total energy & protein with ↑ age
Ageing: insulin and glucose
how does it change
↑ [insulin] and [glucose] with ↑ age
↑ insulin resistance
↓ peripheral glucose uptake
↑ prevalence metabolic syndrome with ↑ age
What is metabolic syndrome and what does it include
what is the underlying mechanism caused by
Constellation of closely associated CV risk factors
Visceral obesity, dyslipidaemia, hyperglycaemia, hypertension
Insulin resistance is the underlying pathophysiological mechanism
Ageing: Menopause
what causes it
symptoms
morbidities associated with it
CAUSE
ovarian failure. oestrogen levels stay very low post menopause. ↓E2, ↑LH / FSH
50 years: hot flushes, night sweats, median duration of menopausal symptoms 7 years
morbidity
↑ osteoporosis, ↑ CHD, ↑ sexual dysfunction
Post menopausal HRT
observational studies
obs studies showed benefits - BUT healthy user bias. risks as well.
risk: benefit ratio depends on
Other risk factors
Age of women and duration of HRT use
Greater risk if >60 years, >10 year post MP
Type of HRT (oestrogen, progestogen, route)
Post menopausal HRT
benefits and risks
BENEFITS: Decreases osteoporosis / fracture risk, for duration Rx
RISKS: ↑ venous thrombo-embolism ↑ breast Ca (small) esp > 5 years ↑ endometrial Ca if use unopposed E2
Male gonadal axis and age
what happens
gradual decr of Testosterone with age
decrease in sexual function
increase in osteoporosis
decrease in muscle strength
Testosterone treatment
what can it do?
Bones: can increase bone mineral density if hypogonadal. bisphosphonates work independant of androgen status
Body composition: incr lean body mass, decr fat mass
increases muscle strength with supraphysiological doses
Testosterone treatment:
benefits and risk and apprasial
Little benefit. no evidence for.
Sexual function: most erectile dysfunction is atherosclerotic.
Cognitive function
Mood / QoL
RISKS
Prostate (benign prostatic hypertrophy / cancer)
Erythropoeisis (haematocrit)
? Cardiovascular risk ?
GH-IGF-I axis and age
decr integrated [GH] with incr age; decr [IGF-I] with age
Wide variation in ‘normal range’
GH treatment
what are the effects
what are the risks
Body:
incr lean body mass
incr fat mass
BUT not convincing functional benefits found. no sig change in bone mineral density and lipids.
RISKS
incr non smoking related cancer risk
incr T2 DM risk
—-soft tissue oedema, arthralgias, carpal tunnel syndrome
Cortisol and age
how? (what is the overall principle of this)
↑ trough levels cortisol with age
↑ in average levels with age
Phase advance of dirurnal rhythm: time at trough and peak both earlier
Increase in cortisol associated with an increased decline in cognitive function. Because less hippocampal glucocorticoid receptors and less sensitivity to glucocorticoid receptors.
More glucocorticoids leads to hippocampal neurones vulnerable to damage. Decreases hippo vol.
DHEA and age: how does it change
how is it regulated and acts
how important is it
declines with age
ACTH regulates
action via androgen / oestrogen release
for men, much more potent androgens - modest androgenic effect at best
DHEA observational studies.
what have they shown and is it relevant?
evidence?
incr in DHEA associated with
↑QOL, ↑bone mineral density,
↓cognitive decline, ↓ coronary heart disease
BUT ↓[DHEA] is a non-specific marker of ill health
- Associations may not be not causal - ↓[DHEA] / ↓ [DHEA]:cortisol ratio found in cancer, inflammatory diseases, T2DM, CV disease
no evidence of beneficial effects in Body composition, physical performance, insulin sensitivity, QOL
