endocrine changes with aging

• Endocrine system


  The system of glands that secrete hormones directly into the bloodstream to regulate the body's growth, metabolism, and sexual function
• Endocrine changes with aging


  Changes in the function and secretion of hormones that occur as people get older
• "The only endocrine system for which there is a well-defined, abrupt, and universal change in function with age is the hypothalamic-pituitary-gonadal axis in women"
• Changes in the HPG axis in women during menopause


  • Ovarian secretion of estrogens decreases
  • Secretion of follicle-stimulating hormone (FSH) and luteinizing hormones (LH) increases

  
• Hormone changes during perimenopausal period


  Associated with autonomic and emotional dysfunctions (e.g. hot flashes, heart palpitations, night sweats, mood swings)

  
• Effects of estrogen on bone


  • ↑hepatic production of IGF-I that stimulates osteoblast differentiation
  • ↑ bone maintenance
  • ↓ production of cytokines (e.g. TNFa and ILs) by bone marrow and immune cells
  • ↑ osteoclastic cell death (via ERa receptors)
  • ↑ secretion of osteoprotegrin (OPG), a decoy receptor for RANKL
  • ↓FSH secretion (through -ve feedback)
  • ↓ osteoclast differentiation and function
  • ↓ bone resorption
• Effects of estrogen on the cardiovascular system


  • ↑ coagulation factors
  • ↑ plasminogen
  • ↑ platelet adhesiveness
  • ↑HDL ↓LDL
  • Supports cardiomyocyte contractility, inhibits apoptosis
  • ↑Dilatation
  • ↑Nitric oxide
  • ↓Atherosclerosis
  • ↓Vascular injury
  • ↑Endothelial-cell growth

  
• Hormone Replacement Therapy (HRT)


  Estrogen-based therapy used during menopause to alleviate symptoms and provide health benefits, but also has some risks

  
• Effects of HRT


  • Good effects: Strengthens bone, Lowers LDL cholesterol, Raises HDL cholesterol, Reduces menopausal symptoms
  • Bad effects: Increases breast cancer risk, Increases uterine cancer risk, Increases blood clot risk
• Changes in the male HPG axis with aging ('andropause')


  • Testicular function declines gradually, Sperm production stable from end of puberty to ~70 years, then declines to ~50% by 90 years
  • Accompanied by tubular fibrosis, shrinkage of testicular volume, and modest elevations of FSH
  • Declining testosterone levels may play a role in the osteoporosis and sarcopenia of the elderly

  
• Potential benefits of testosterone supplementation


  • Improvements in bone density, muscle mass and strength
  • Decreases in central adiposity and insulin resistance
  • Improvements in libido and erectile function
  • Better scores on cognition and memory tests
• Potential disadvantages of testosterone supplementation


  • Adverse effects on lipid profiles (increased CV disease and polycythemia risk?)
  • Worsened sleep apnea
  • Increased risk of prostate cancer
  • Detrimental effects on CNS (with supraphysiological levels)

  
• Changes in adrenal hormones with aging


  • DHEA secretion decreases from 3rd decade onwards
  • Diminished production of adrenal androgens (e.g. DHEA) thought to contribute to loss of bone density and muscle mass
  • Serum concentrations of cortisol tend to be more variable, with higher evening nadir and 20-50% higher mean 24-hour concentrations
  • Serum cortisol responses to stress are prolonged
  • Secretion rate and serum concentrations of aldosterone fall with age

  
• Growth hormone (GH) and IGF system changes with aging


  • GH secretion and serum GH/IGF-1 concentrations fall with age
  • Decreased GH secretion due to decreased GHRH secretion and pituitary responsiveness
  • Age-associated sleep disturbances and decreased physical fitness also contribute to decreased GH

  
• Potential benefits of GH-sex steroid supplementation


  • Increased lean body mass
  • Decreased adiposity
  • Improved muscle strength & VO2 max (in men)
• Adverse effects of GH-sex steroid supplementation


  • Edema
  • Carpal tunnel syndrome
  • Arthralgias (joint pain)
  • Increased risk of diabetes (increased glucose intolerance)
• Changes in thyroid function with aging


  • No age-related changes in serum total or free thyroxine concentrations
  • Thyroxine production and clearance both decrease modestly
  • Thyroid dysfunction occurs more frequently in older populations
• Vitamin D changes with aging


  • Mild vitamin D deficiency is common in older subjects
  • Vitamin D deficiency contributes to reduced bone density, reduced strength and increased fracture risk
• Calcium balance changes with aging


  • Calcium balance is often negative in older subjects
  • Calcium loss is further accelerated in elderly persons with hyponatremia
• Changes in parathyroid hormone (PTH) with aging


  • Serum PTH concentrations are slightly higher in older subjects, likely due to phosphate retention and mild vitamin D deficiency
• Circadian rhythm disturbances with aging


  • Early onset of sleep and awaking very early in the morning
  • Non-dipper blood pressure pattern (BP does not fall lower at night)
  • Shifts in timing and magnitude of ACTH, TSH, and GH rhythms
  • Altered circadian rhythm of food intake
• Decreased hormone action with aging


  • Vasodilatory response to estrogen reduced
  • Leydig cells become less responsive to gonadotropin stimulation
  • Serum noradrenaline concentrations higher as compensation for decreased responsiveness
  • Vasopressin secretion increased but renal responsiveness decreased, leading to dehydration

  
• Chronic hyponatremia in the elderly


  • Common problem, particularly in women
  • Contributory factors: hypersecretion of vasopressin, aldosterone deficiency, renal tubular dysfunction
  • Associated with CNS impairment and accelerated calcium loss from bone
• Sarcopenia and osteoporosis with aging


  • Age-related loss of muscle mass/strength and bone mass
  • Contribute to weakness, decreased activity, loss of independent living, fractures
  • Endocrine changes (sex steroids, GH/IGF, etc.) and low-grade inflammation are major contributors
• Changes in glucose metabolism with aging


  • Insulin resistance increases
  • Glucose clearance tends to be decreased
  • Some have hyperinsulinemia, others have hyperproinsulinemia
  • Incidence of type 2 diabetes is higher in older adults
• Changes in lipid and protein metabolism with aging


  • Dyslipidemia (hypertriglyceridemia, high LDL, low HDL) more prevalent
  • Hyperuricemia and increased incidence of gout

  
• Key endocrine changes with aging


  • Menopause (estrogen ↓, progesterone ↓)
  • Andro'pause' (testosterone ↓)
  • Somatopause (GH ↓, IGF ↓)
  • Adreno'pause' (DHEA ↓, cortisol ↑, aldosterone ↓)
  • Synchro'pause' (melatonin ↓)

  
• Endocrine changes with aging


  Contribute to sarcopenia/reduced lean body mass, osteoporosis, sleep disturbances, reduced libido, metabolic alterations, and increased incidence of age-related diseases including thyroid disease