Treatment of PCOS Flashcards
Metabolic defect associated with PCO
Insulin Resistance
What is insulin resistance?
body is producing insulin but not able to use it effectively (i.e. muscle, fat and liver), hence in order to keep blood glucose in normal range beta-pancreatic cells produce more and more insulin – hyperinsulinemia
How is IR different to type 2 diabetes?
circulating insulin levels increase to compensate = hyper-insulinaemia
PCOS and central adiposity
Women with PCOS have central adiposity, which is linked to IR. May NOT be due to higher relative percentage of visceral fat
In animals exposure to androgens is associated with
increased fat accumulation
Transsexuals and adiposity
Treatment with high androgens in female-to-male transsexuals increases visceral fat accumulation
Insulin sensitivity in relation to weight
Although everyone becomes more insulin resistant with increasing weight » insulin sensitivity declines at a faster rate in women with PCOS than in women with normal ovaries with increasing weight
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?
Describe the signalling mechanism of insulin
How is IGT measured?
Oral glucose tolerance test to determine IGT
Fasting 8-12h before test → glucose given as a solution → blood samples taken (0-2h) to determine how quickly cleared from blood
Results of OGTT
Normal: Fasting value (before test): <5.6 mM;
At 2 hours: between 6-7.8 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
Obesity exacerbates many aspects of PCOS clinical, hormonal and metabolic features in women
If patient has oligomenorrhea & hyper-androgenism in adolescence then increased risk of developing obesity & MetS by 24y
30-40% women with PCOS have impaired glucose tolerance (IGT) and 10% develop T2DM by age 40yrs
Higher incidence of T2DM in women with family history i.e. Indian sub-continent Asians
Obesity & insulin resistance results in:
increased incidence of Gestational Diabetes M
why would it present first in pregnancy?
Gestational Diabetes Mellitus (GDM)
Placenta produces E, cortisol & human placental lactogen
↓
HPl interferes with insulin receptors
↓
Maternal Hyperglycemia
↓
Increased glucose in maternal circulation crosses to foetal circulation
↓
Increase in fetal insulin
↓
Excess fetal growth – large for gestational age
GDM and increased risk of childhood obesity
Unfortunately, excess insulin produced by the fetus in response to the mother’s gestational diabetes can cause the fetus to grow excessively, a condition known as large for gestational age. For fetus they are large for age and low blood sugar and increased risk of childhood obesity.
Complications of GDM for mother and foetus
Even if glucose goes back to normal after pregnancy, have an increased risk of T2D
If already IR and then pregnant, it induces increase in GDM risk, pre-eclampsia and later T2D.
Unpublished data from SGH, showed that nearly all women with GDM had PCO.
The oral glucose challenge test (OGCT) is a short version of the OGTT, used to check pregnant women for signs of gestational diabetes.[3][13] It can be done at any time of day, not on an empty stomach.[3] The test involves 50g of glucose, with a reading after one hour
IR and anovulation
There is a direct inverse relationship between hyperinsulinemia and ovulation rate.
Also we know that high insulin levels can have a detrimental effect on follicles
Other manifestations of metabolic defect in PCO:
tendency to obesity with increase in truncal-abdominal fat
increased hypertension
Altered lipid profile
apparent increased risk for atherosclerotic disease
Recent study showed that women with PCOS at ↑risk of osteosarcopenia
Altered lipid profile
higher levels of LDL cholesterol – regardless of BMI
low levels of HDL cholesterol and elevated triglycerides
apparent increased risk for atherosclerotic disease
Increased coronary artery calcification (independent of age & BMI)
Increased carotid artery intima-media thickness (predictor of stroke & MI) compared to age-matched controls
Limited longitudinal studies → PCOS diagnosed during reproductive lifespan (20-30 years old) but CVD manifests 30 to 40 years later.
Also majority of conducted research on CVD on male →concept that women present differently
Osteosarcopenia
newly described syndrome that describes the co-existence of osteoporosis and sarcopenia, two chronic musculoskeletal conditions associated with ageing. Osteoporosis, a condition of low bone mass and micro-architectural deterioration of bone, and sarcopenia, the loss of muscle mass, strength and function, often co-exist in a frail subset of the elderly population, leading to significantly worsened outcomes than seen in either condition alone.
Why do women with PCOS gain weight?
Constant tendency to gain weight:
Normal-weight women with PCOS consistently maintain a lower-calorie diet than their over-weight counterparts
HRQoL study in women with PCOS → normal-weight women experienced as many problems with their weight as obese women.
WHY? Are women with PCOS more inclined to put on weight or is it parallel to growing obesity epidemic?- both
PCO is associated with reduced energy expenditure equivalent to over 17,000 kcal/pa
PCOS and PPT
PCOS is associated with reduced energy expenditure
this is due to reduced post-prandial (after eating) thermogenesis (PPT)
it is amplified by obesity in PCOS
Insulin sensitivity is reduced in both obese & lean women with PCOS compared to normal
Why is it important to tackle PCOS earlier on?
If you go and see your GP in your teens, they usually tell you to go away and come back when you want a baby, or your cycles will settle down in a bit.
By the time the patient is in their 20s they’ve put 1.9kg/year which complicates the situation and make it very hard to loose weight, get regular cycles etc.
