Endocrinology of ageing Flashcards
Which three perspectives must be explored when discussing ageing?
- Evolutionary perspective
- We are outliving our natural lifespan: menopause, andropause, somatopause, adrenopause - Cultural perspective
- Pharma perspective
LIFE EXPECTANCY MAY NOT EQUATE TO INCREASE HEALTH EXPECTANCY
- Association isnt causation. Similar phenotype of disease state to ‘elderly syndromes’ but that doesnt mean they are CAUSING them.
How does nutritional status vary as we age?
Weight: Increases from 35
Lean body mass: Decreases by 6-8%/ annum from 35
Diet: Lower total energy intake and protein with increased age
How does insulin/ glucose vary as we age?
[ Insulin ] and [ glucose ] increase with age
- Increased insulin resistance
- Decreases peripheral glucose uptake
- Increased prevalence of metabolic syndrome (more likely in men)
What is menopause?
What changes occur?
Symptoms?
Morbidity?
Ovarian failure occuring in women as a mean age of 50 (brain and ovaryr are ‘pacemakers’)
- Decrease in E2, Increase in LH/ FSH
Pre-menopausal: oestrogen levels are cyclin, post: low constant level - Hot flushes, night sweats, lasting 7 years (on average)
- Increased osteoporosis, CHD, sexual dysfunction
Consider post menopausal HRT (oestrogen and progesterone)
Outline the advantages and disadvantages of its use
ADVANTAGES: (Benefits depend on other risk factors e.g. age of woman and duration of HRT use)
- Reduces menopausal symptoms
- Decreases osteoporosis/ fracture risk for duration of use
DISADVANTAGE: (Greater if >60 years old)
- Increases venous thromboembolism
- Increases breast cancer (small), especially if >5 years
- Increases endometrial Ca (if used unopposed E2)
Consider post menopausal HRT (oestrogen and progesterone)
Discuss how the goal of treatment has shifted
- From ‘replacement’ (to prevent disorders associated with post-menopause oestrogen deficiency e.g. osteoporosis)
- to ‘treatment’ of menopausal symptoms
(Short term, lowest effective dose, younger menopausal women)
How does the male gonadal axis vary with age?
- Gradual decline in [testosterone]
- Wide range of normality of all ages
- At 75 years old, mean [testo] approximately 2/3 of that at 25 y/o
- Poor associatation bwteen libido/ erectile dysfunction and [teso]
- Testosterone prescription increase by 500% over the past decade
State the three symptoms of clinical hypogonadism?
- Decreased sexual function
- Osteoporosis
- Decreased muscle strength
What are the effects of testosterone treatment on bones and body composition?
BONE:
- Increased bone mineral density, potential effect on fracture risk?
- Bisphosphates work independently of androgen status
BODY COMPOSITION
- Increased lean body mass
- Lower fat mas
- No functional benefits
- Increased muscle strength with supra-physiological doses
POSITIVE CORRELATION BETWEEN TESTOSTERONE AND WEIGHT LOSS
What are the potentia risks and problems associated with taking exogenous testosterone?
How should the use of this type of treatment be approached?
- Little/no evidence of benefit/insufficient data on atheroclerosis/ CAD, sexua function, cog function, mood
Rx:
- Prostate (benign prostatic hypertrophy/ cancer)
- Erythropoeisis (increased haematocrit)
- CVD?
Approached with pragmatism and approprate reserve and avoid suggesting/ soliciting symptoms.
How does the GH-IGF-I axis vary with age?
What are the effects of treatment?
Potential risks?
Side effects?
- Less GH and IGF-1 with age
- Treatment leads to increased body mass (approx 2kg), decreased fat mass (2kg), no significant chnage on bone mineral density and lipids
- Increase incidence of cancer: High [IGF-1] in observational studies is associated with increased risk non-smoking related Ca (prostate, colon, breast)
- Increased incidence of T2DM
- Soft tissue oedema, arthralgias, Carpal tunnel
How does the HPA axis vary with age?
- High trough levels cortisol with increasing age (higher average levels of cortisol with age)
- Phase advance of diurnal rhythm - time of trough and peak is earlier (hence why older people wake up earlier)
Briefly describe the Sapolsky’s glucocorticoid cascade hypothesis (Principle not detail)
- Fewer hippocampal glucocorticoid and mineralocorticoid receptors
- Reduced sensitivity to GC negative feedback
- Increased [ glucocorticoids] –> Hippocampal neurons vulnerable to damage
- ’ feed forward cascade’ - reduced volume hippocampus on MRI (no differences in volume of adjacent structures)
- Other roles of hippocampus: learning, memory affected?
(High [cortisol] associated with increased decline cognitive function)
What happens with dehydroepiandrosterone (DHEA) with age?
How is its action regulation?
How is it used in the USA? Effects of this kind of use?
DECLINE with age
- Regulation of DHEA: ACTH? Action via androgen and/or oestrogen R? Is it a pro-hormone?
- More potent circulating androgens in men–> contribution to androgenic effects in men (modest)
DHEA is a food supplement regulated by the FDA in the USA (readily available)
- no evidence of benificial effects on body composition, physical performance, insulin sensitivity, QOL
- no adverse effects
How does thyroid function vary in age?
- Slight increase [TSH] with age
- Decrease in peripheral T4 –> T3 conversion
- Decrease [T3] (no evidence of benefit of T4 treatment, risk of AFib, osteoporosis)
- [T4] steady
What happen to glucose and insulin in starvation/anorexia nervosa?
Role of LEPTIN?
Ob/ob mouse?
Leptin treatment?
Decreased insulin and glucose and increase insulin sensitivity
- LEPTIN produced by white adipose tissue reports nutritional information to the hypothalamus. Low [Leptin] leads to increased food intake, less energy expenditure and fertility
(Leptin in a permissive factor for initiation of puberty)
Therefore in these states: Low LH, FSH, oestrogen/ testosterone reducing fertility and causing amenorrhoea (‘hypothalamic’- brain detects ill environment for baby’)
RISK OF OSTEOPOROSIS
Ob/ob mouse had low gonadaotrophins –> incomplete development of reproductive organs –> infertility
Reduces obesity, restores GnRH secretion, matures gonad, induces puberty, restores fertility
Describe kisspeptin as the central mediator of GnRH
- Its a GnRH secretagogue
- KISS1 neurons highly rsponsive to oestrogen, implicated in both positive and negative central feedback of sex steroids on GnRH production
- Metabolic influences on reproduction mediated by LEPTIN via kisspeptin system (puberty and reproduction)
What happen to the GH IGF-1 axis in starvation and anorexia nervosa?
Effect of thyroid function?
-‘GH resistance’ - increased GH, low IGF-1
Seen in acute starvation and anorexia nervosa
- Down regulation hepativ GH receptor and post-receptor defect?
- Reversible with refeeding
TSH & T4 lower limit of normal
- Decreased T4 conversion to T3 –> decreased T3 circulating (active form)
- Increased T4 conversion to rT3 (inactive)
- This decreases the basal metabolic rate conserve energy
