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Polycystic Ovarian Disorder

Polycystic Ovarian Disorder. Max Brinsmead PhD FRANZCOG April 2013. Criteria for the diagnosis of PCO. Has been controversial… In the US the NIH states that it is: Menstrual abnormalities and anovulation Cinical or biochemical evidence of androgen excess And the exclusion of:

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Polycystic Ovarian Disorder

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  1. Polycystic Ovarian Disorder Max Brinsmead PhD FRANZCOG April 2013

  2. Criteria for the diagnosis of PCO • Has been controversial… • In the US the NIH states that it is: • Menstrual abnormalities and anovulation • Cinical or biochemical evidence of androgen excess • And the exclusion of: • Prolactin excess, thyroid disorder, congenital adrenal hyperplasia & Cushings syndrome

  3. Criteria for the diagnosis of PCO • In 2003 a European Consensus statement simplified this to… • Any two of the following: • Menstrual abnormalities and anovulation • Cinical or biochemical evidence of androgen excess • Polycystic ovaries on ultrasound • (Transient states e.g. adolescence and simple obesity need to be excluded)

  4. But what is PCO for the practising doctor? • A genetic variant that affects 5 – 10% of the female population • Manifests itself as different problems at different stages of adult life • Can vary in severity from mild to severe • Best regarded as an evolutionary variant that has permitted survival of the species during times of famine • The problem is that there are few famines in the developed world in the 21st century!

  5. Common clinical manifestations of PCO • Obesity • Hirsutism or Acne • Menstrual irregularity • Infertility • Type 2 diabetes • Dyslipidaemia

  6. Other manifestations of PCO • Axillary/Groin Follicular Adenitis • Premature pubarche • Bulimia • Acanthosisnigrans • Recurrent miscarriage • Frontal balding or clitoromegaly • Homosexuality • Cardiovascular disease • Endometrial hyperplasia and cancer

  7. Essential Tests for possible PCO • Ultrasound of pelvis • More than 12 follicles 5 – 10 mm diam in one or both ovaries • NB 20% of cycling women have “polycystic ovaries” • Serum androgens • Must measure free testosterone or equivalent • Fasting glucose, cholesterol & triglycerides • Preferably measure insulin as well • Exclude other causes of the presenting problem • Prolactin, Thyroid function, HydroxyPROG or dexamethasone suppression as clinically indicated

  8. Laboratory Manifestations of PCO • Elevated free testosterone or free androgen index • Hyperinsulinaemia • Elevated LH or raised LH:FSH ratio • Mild chronic hyperoestrinism • Elevated CHOL, LDL or triglycerides • Elevated tissue plasminogen activators • Evidence of low grade chronic inflammation • (Measures of serum leptin correlate with obesity and not PCO)

  9. Management of the PCO Disorder • Will depend on the principal problem… • Hirsutism • Menstrual dysfunction • Infertility • Obesity • Diabetes and or Dyslipidaemia

  10. Management of Hirsutism • Is primarily cosmetic • Shaving • Waxing • Dye or Depilation • Spironolactone • Cyproterone acetate (Androcur) • Combined oral contraceptive • Preferably with cyproterone acetate e.g. Diane • Other measures • Ketoconazole • Flutamide (not available in Australia) • Topical Eflornithine ( “ “ “ “ )

  11. Management of menstrual dysfunction due to PCO Disorder • Diet, exercise and lifestyle changes if obese • Combined oral contraceptive • Use 3rd or 4th generation or cyproterone acetate e.g. Diane • Contraindicated if >35 years AND smoking or morbidly obese • Mirena IUS is a good alternative • Cyclical or continuous progestin • Depot provera • An alternative for those who do not want “the pill” • There may be a role for Metformin • Endometrial resection • Hysterectomy

  12. Management of Infertility due to PCO Disorder • Diet, exercise and lifestyle changes if obese • Is as effective as drugs! • Clomiphene citrate (Clomid) • Metformin • Ovarian drilling • FSH and HCG • IVF and ET

  13. Management of Obesity and Dyslipidaemia with PCO Disorder • Diet, exercise and lifestyle changes • Metformin • A possible role for Glitazones • Sustained release Metformin may improve compliance

  14. So is Metformin the panacea for PCO Disorder? • Results from combined trials: • Decrease androgens by a mean of 20% • Increase ovulation from a mean of 1:5 months to 2:5 months • Decrease BMI by a mean of 4% • So the outcomes are modest

  15. Problems in the use of Metformin for PCO Disorder • There are relatively few large scale and long term studies • Is not as effective as lifestyle changes in RCTs • Nausea and diarrhoea are common • A small risk of hepatoxicity, lactic acidosis and B12 deficiency • May be teratogenic if used in pregnancy

  16. So what is the role of Metformin in PCO Disorder? • To encourage weight loss • Non significant effect in meta analysis of RCT’s • To enhance the effectiveness of Clomid • Non significant effect in meta analysis of RCT’s • Improves egg and embryo quality during IVF • Pregnancy rates doubled and risk of miscarriage reduced • Reduces the risk of OHSS during IVF • 4Xfold reduced risk • May prevent the onset of Type 2 Diabetes • Does reduce the risk of cardiovascular disease when used for Type 2 Diabetes • So the long term use remains controversial

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