Endocrine Control Female Reproduction 9 Flashcards

Describe the metabolic abnormalities of PCOS.

1
Q

What are the metabolic findings in PCOS?

A
  • Insulin resistance
  • Pancreatic beta-cell dysfunction
  • Obesity
  • Risk factor for metabolic syndrome:
    • CV disease risk factors
    • associated with visceral adiposity and insulin resistance
    • also linked with type 2 DM
  • Other risks:
    • gestational diabetes
    • pre-eclampsia
    • sleep apnea
    • non-alcoholic fatty liver disease
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2
Q

Is insulin resistance the cause of obesity in PCOS? Or the other way around?

A
  • Mostly due to peripheral and hepatic insulin action and beta-cell dysfunction
  • Obesity worsens parameters but is independent
  • In some populations, such as those from Scandinavia, obesity may account for insulin resistance
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3
Q

How is the molecular mechanism in PCOS unique?

A
  • No mutations in the coding portion of insulin receptor gene have been found in PCOS
  • Post-binding defect in insulin signaling
  • Due in part to increased serine phosphorylation of the insulin receptor and downstream signaling
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4
Q

What is the relationship between the metabolic and reproductive abnormalities of PCOS?

A
  • Insulin stimulates ovarian androgen production in synergy with LH
  • Action appears to be mediated by insulin acting through its cognate receptor
  • Insulin can stimulate adrenal androgen production by enhancing sensitivity to ACTH
  • Pre-existing PCO changes such as theca cell hyperplasia required for insulin-mediated ovarian hyperandrogenism
  • Other contributing factors aside from insulin
  • Blocking androgen action with a receptor antagonist in women with PCOS can improve insulin sensitivity
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5
Q

What effect of insulin on the brain is implicated in PCOS?

A
  • Insulin-sensitizing drugs can restore ovulation in women with PCOS
  • Central insulin sensitivty
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6
Q

What is the effect of prenatal androgen exposure?

A
  • Can reproduce the reproductive and metabolic features of PCOS in animal models
  • Similar in humans:
    • permanently alters LH secretion
  • Exposure later in development between childhood and puberty can also program PCOS features
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7
Q

What is the evidence for genetic susceptibility in PCOS?

A
  • ~40% clustering of reproductive age sisters with PCOS are affected with hyperandrogenemia
  • Twin studies show a correlation of 0.71 between monozygotic twins and 0.38 between dizigotic twins
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