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
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
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
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
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
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
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