Treatment of PCOS Flashcards
What metabolic defect is associated with PCOS ?
Insulin resistance is the central feature of the PCOS metabolic defect
What is meant by insulin resistance and how does this differ to type 2 diabetes
Insulin resistance is also known as pre-diabetes
It is different to type 2 diabetes because insulin is released however the body is resistance to insulin.
Insulin resistance is when cells in your muscles, fat, and liver don’t respond well to insulin and can’t easily take up glucose from your blood
-Hyperinsulinemias
Outline the progression of insulin resistance in PCO
Initially there will be hyperinsulinemia as the circulating insulin levels increase to compensate.
This aims to maintain euglycaemia which is the normal levels of glucose.
Eventually to maintain this euglycaemia we have to keep increasing the level of insulin to do the same thing.
During this time the action of insulin will decrease. There will eventually be B-cell insufficiency as they will become fatigued.
This will then lead to diabetes eventually.
How does weight affect insulin sensitivity in PCO ?
There insulin sensitivity will decrease at a faster rate.
At the same weight it will be much faster and they will have a lower insulin sensitivity
What kind of fat do PCO have ?
They have more central adiposity as opposed to visceral fat.
What pathway is disrupted and defected in insulin resistance ?
There was no mutation found in the insulin receptor gene in PCOS .
A post-receptor binding defect was found somewhere in signalling pathway in granulosa cells.
This was in the pathway which allows for GLUT 4 (vesicle which gets inserted into the membrane) had a defect.
This means there is no glucose entering the cell.
There will be a release of macrophages and cytokines which cause inflammation and can dysregulate the pathway ,
In what ways can obesity exacerbate the aspects of PCOS clinical ,hormonal and metabolic features ?
If the patient has oligomenorrhea and hyper androgenism in adolescence then there is an increased risk of developing obesity and Metastatic cancer by the age of 24 years old.’
Around 30-40% of women with PCOS will have impaired glucose tolerance and around 10% will develop Type 2 Diabetes by age 40 years
How can we determine if someone has impaired glucose tolerance ?
We can use an oral glucose tolerance test.
It is done by letting the patient fast for around 8-12 hours before test- glucose is given as a solution and blood samples (0-2 h) are taken to determine how quickly it is cleared from the blood.
How does gestational diabetes mellitus arise ?
This will occur due to hormones being produced by the foetus.
The placenta will produce oestradiol . cortisol and human placental lactogen.
HPL will interfere with insulin receptors making the mother hyperglycaemic.
Increased glucose in maternal circulation crosses to foetal circulation
Increase in foetal insulin
Excess foetal growth =Large size for gestational age
How does gestational diabetes mellitus arise ?
This will occur due to hormones being produced by the foetus.
The placenta will produce oestradiol . cortisol and human placental lactogen.
HPL will interfere with insulin receptors making the mother hyperglycaemic.
Increased glucose in maternal circulation crosses to foetal circulation
Increase in foetal insulin
Excess foetal growth =Large size for gestational age
How is insulin linked with anovulation ?
As the serum insulin increases the number of menstrual cycles per year will decrease
What are some of the manifestations of metabolic defect in PCO ?
There is a tendency to obesity with increase in truncal abdominal fat
Increased hypotension
Altered lipid profile:
(Higher levels of LDL cholesterol )
(Low levels of HDL cholesterol + elevated triglycerides )
Apparent increased risk for atherosclerotic disease
What causes weight gain in woman with PCOS?
The constant tendency to gain weight is due to reduced energy expenditure.
PCOS is associated with reduced energy expenditure
This is due to reduced post-prandial thermogenesis
( metabolic process by which organisms burn calories in order to generate heat.)
It is amplified by obesity in PCOS
How do SHBG levels change in PCOS ?
SHBG is sex hormone binding globulin .
It binds antigens so there is a majority of testosterone which will be bound to SHBG.
There will be a small change in SHBG which causes a large change in free testosterone.
SHBG is dependent on BMI ie obesity will cause low SHBG and high free T.
SHBG production in the liver is inhibited by insulin which stimulates LH which leads to androgen production
