12. Endocrinology of aging Flashcards
Determinants of age
• Nutritional status • Insulin/glucose • Gonadal axis ○ Menopause/ andropause • GH-IGF system • Cortisol • DHEA • Thyroid function Diet Starvation Anorexia nervosa • Insulin/glucose • Leptin • Gonadal axis • GH-IGF system • Cortisol • Thyroid function
Different perspectives
• EVOLUTIONARY PERSPECTIVE • We are outliving our natural lifespan • Hormonal function: ○ ‘MENOPAUSE’ ○ ‘ANDROPAUSE’ § ‘ADAM’ ○ ‘SOMATOPAUSE’ ○ ‘ADRENOPAUSE’ • Cultural perspective ○ Anti-aging results in 2,940,000 Google hits • Pharma perspective ○ Enormous market, especially compared to endocrine market for testosterone/GH
Medicalisation of ageing
• Increased life expectancy may not equate to increased health expectancy • Usual ageing ○ Physiological - normal? ○ Pathological? ○ Optimal? • Boundaries of medicine? • Hormonal influence? ○ Dwarfed by: ○ Genetic, environmental, psychosocial, co-morbidities • Balance of benefit & harm of treatment ○ Risks esp cancer risk in elderly ○ Hassle - GH/testo not orally active ○ Costs
Association and causation
Similar phenotypes
• Hypogonadism/growth hormone deficiency/ aging
• Increased fat mass, increased visceral fat
• Sarcopaenia
• Decreased bone mineral density
• Decreased quality of life an mood
• Increased risk of cardiovascular disease
Phenotypes are non-specific, high prevalence - maybe universal
Age: nutritional status
Weight - increases from mid-30s up to 50-70
Lean body mass - decreased 6-8%/decade from mid 30s
Diet - trend towards decreased intake total energy and protein with increasing age
Age: insulin/glucose
• ↑ [insulin] and [glucose] with ↑ age
○ ↑ insulin resistance
○ ↓ peripheral glucose uptake
• ↑ prevalence metabolic syndrome with ↑ age
Metabolic syndrome
‘Constellation of closely associated CV risk factors’
• Visceral obesity
• Dyslipidaemia
• Hyperglycaemia
• Hypertension
INSULIN RESISTANCE is the underlying pathophysiological mechanism
Menopause
Menopause = ovarian failure • Oestrogen levels ○ Pre-menopausal: cycling ○ Post-menopausal: very low constant levels § ↓E2, ↑LH / FSH • ? Brain & ovary are ‘pacemakers’ ○ Age at menopause 50 ± 2 years • Symptoms: ○ Hot flushes, night sweats ○ Median duration of menopausal symptoms 7 years • Morbidity: ○ ↑ osteoporosis, ↑ CHD, ↑ sexual dysfunction
Post-menopausal HRT
Initial observational studies showed benefits
• ‘healthy user bias’
Some subsequent RCTs showed no benefits and increased risks
• However risk : benefit ratio depends on
○ Other risk factors
○ Age of woman and duration of HRT use
§ greater risk if >60 yrs, >10 year post-MP
○ Type of HRT (oestrogen, progestogen, route)
Post-menopausal HRT benefits and risks
Benefits:
• Rx menopausal Sx
• Decreased osteoperosis/fracture risk for duration Rx
Risks
• Increased venous thrombo-embolism
• Increased breast cancer (small) esp > 5 years
• Increased endometrial cancer if use unopposed E2
Post-menopausal hormone therapy treatment goals
Goal of treatment shifted back:
• From replacement to prevent disorders associated with post-menopausal oestrogen deficiency, like osteoperosis
• To treatment of menopausal symptoms - short term, lowest effective dose, younger menopausal women
Male gonadal axis
Different for men
Gradual decrease in testosterone with increased age
Wide range of normality at all ages
@75 years, mean [testo] is 2/3 that @ 25 years
Poor association between libido/erectile dysfunction and [testo]
Testosterone prescriptions increased 500% over the past decade
Age: male gonadal axis
Clinical hypogonadism
• ↓ sexual function
• ↑ osteoporosis
• ↓ muscle strength
Testosterone treatment effects on bones?
Bones
• Increase in bone mineral density if hypogonadal
• ? effect on fracture risk ?
• Bisphosphonates work, independent of androgen status
Testosterone treatment on body composition
- Increase in lean body mass
- Decrease in fat mass
- No convincing functional benefits demonstrated
- Increase in muscle strength with supra-physiological doses
