Estrogen and Human Disease

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Estrogen and Human Disease

• Estrogen receptor deficient male
• Open epiphyses
• Atherosclerosis premature coronary artery
  calcification at age 31

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Aromatase Deficient Male

• 27 year old male
• Parents (2nd cousins) heterozygous for mutation
  in CYP19 (aromatase) gene
• Heterosexual, normal libido
• Height 197 cm (about 66)

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Aromatase Deficient Male
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Treatment with Estradiol Injections

• 50 ?g transdermally 2 times/week for 3 months
• 25 ?g transdermally 2 times/week for 3 months

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Results

• Semen analysis oligoazospermia (numbers
  conflicting and unclear)
• Sperm count decreased following E2
• Sperm motility ?

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Results

• Total cholesterol low
• LDL/HDL ratio initially 5.37
• Reduced to 3.56 after E2 treatment
• Low HDL puts patient at risk of atherosclerosis

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Results

• BMD low (52 mg/cm3)
• Increased following E2 treatment (83 mg/cm3)
• Bone epiphyses open 16.5 yr old
• Following E2 treatment epi nearly closed

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Results

• Insulin and blood glucose elevated and both
  decreased following E2 treatment

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Estrogen Receptor and Human Disease
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Selective Estrogen Receptor Modulators (SERMs)

• Tamoxifen
• Agonist in uterus and bone
• Antagonist in breast tissue
• Raloxifene
• Similar to tamoxifen but greater agonist in bone
  and less in uterus

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Breast Cancer

• Both SERMs (tamoxifen and raloxifene) and
  aromatase inhibitors used in ER positive breast
  CA
• SERMs also used as preventative in high risk
  females

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ER and Osteoporosis

• E2 increases bone density in both males and
  females
• Lack of E2 leads to bone loss
• Menopause, ER insensitivity, Aromatase deficiency
• E2 or raloxifene prescribed for osteoporosis

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ER and Neurogenerative Disease

• In general, estrogens are neuroprotective in
  humans
• Stroke
• Pre-menopausal women have fewer than age-matched
  men
• Post-menopausal women same as men

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ER and Neurogenerative Disease

• Alzheimers Disease
• Pre-menopausal women have fewer than age-matched
  men
• Post-menopausal women same as men
• Parkinsons Disease
• More prevalent in males than females

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Obesity

• Increases after menopause