Treatment of PCOS Flashcards
What metabolic defect is associated with PCO/PCOS?
Insulin resistance - it’s not part of the diagnostic criteria but its prevalent
How is it different to Type 2 diabetes?
- initially glucose levels are low
- circulating insulin levels increase to compensate = hyper-insulinaemia
- Insulin levels increase to try and maintain steady glucose but the insulin doesn’t work well
- so the insulin and glucose levels increase eventually
- beta cells get fatigued, no more insulin made, the whole system breaks and the person is known as diabetic
What is insulin sensitivity like in PCOS?
- insulin sensitivity declines at a faster rate in women with PCOS than in women with normal ovaries with increasing weight
- Insulin sensitivity is reduced in both obese & lean women with PCOS compared to normal
What do women with PCOS have that is linked with insulin resistance?
- Women with PCOS have central adiposity, which is linked to IR
- May NOT be due to higher relative percentage of visceral fat – visceral fat is more dangerous
What is the molecular mechanism of IR in PCOS:
insulin resistance is familial
- No mutations in insulin receptor gene found in PCOS
- Post-receptor binding defect somewhere in signalling pathway in granulosa cells
- Steroid pathway is maintained but signalling pathway that allows glucose to be stored and taken in from the blood stream is affected
What can IR lead to?
IR leads to inflammation and inflammatory markers also play a role in dysregulating the glucose pathway
What can exacerbate symptoms of obesity?
Obesity
What is IGT?
impaired glucose tolerance - seen in may patients with PCOS
What can obesity and IR result in?
o increased incidence of GDM (gestational diabetes)
What relation does type 2 diabetes have with PCOS?
some PCOS patients develop it by age 40
What is OGTT?
Oral glucose tolerance test
What is OGTT used for?
to determine IGT
How is an OGTT carried out?
→ Fasting 8-12h before test
→ glucose given as a solution
→ blood samples taken (0-2h) to determine how quickly cleared from blood
OGTT results for normal glucose tolerance, impaired glucose tolerance and diabetics?
Normal: Fasting value (before test): <6 mM;
• At 2 hours: <7.8 mM
Impaired: Fasting value (before test): 6.0 -7.0 mM;
• At 2 hours: 7.9-11.0 mM
Diabetic: Fasting value (before test): >7.0 mM;
• At 2 hours: >11.0 mM
How does Gestational Diabetes Mellitus (GDM) happen?
Placenta produces E, cortisol & human placental lactogen
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HPl interferes with insulin receptors
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Maternal Hyperglycemia
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Increased glucose in maternal circulation crosses to foetal circulation– if mother was already IR, this makes it worse, insulin will be even higher
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Increase in fetal insulin
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Excess fetal growth – large for gestational age
What issues can GDM cause?
- Pre-eclampsia
- shoulder birth injury
- premature birth
- very high birth weight
What is IR linked to and why?
Anovulation
- There is a direct inverse relationship between hyperinsulinemia and ovulation rate.
- Also high insulin levels can have a detrimental effect on follicles
What are other manifestations of metabolic defect in PCO:
- tendency to obesity with an increase in truncal-abdominal fat
- increased hypertension
• Altered lipid profile:
o higher levels of LDL cholesterol – regardless of BMI
o low levels of HDL cholesterol and elevated triglycerides
• apparent increased risk for atherosclerotic disease
o Increased coronary artery calcification (independent of age & BMI)
o Increased carotid artery intima-media thickness (predictor of stroke & MI) compared to age-matched controls
Why are women with PCOS more inclined to put on weight?
PCOS is associated with reduced energy expenditure equivalent to over 17,000 kcal/pa
- this is due to reduced post-prandial thermogenesis (PPT): the loss of energy after eating a meal
- it is amplified by obesity in PCOS
What is SHBG?
sex hormone binding globulin
