Endocrine Control Female Reproduction 9

Question 1

What are the metabolic findings in PCOS?

Answer 1

• 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

Question 2

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

Answer 2

• 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

Question 3

How is the molecular mechanism in PCOS unique?

Answer 3

• 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

Question 4

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

Answer 4

• 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

Question 5

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

Answer 5

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

Question 6

What is the effect of prenatal androgen exposure?

Answer 6

• 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

Question 7

What is the evidence for genetic susceptibility in PCOS?

Answer 7

• ~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