Transcript Blood Group Incompatibility in Pregnancy

Polycystic Ovarian Disorder
Max Brinsmead MB BS PhD
August 2014
Criteria for the diagnosis of PCO
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Has been controversial…
In the US the NIH states that it is:
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Menstrual abnormalities and anovulation
Cinical or biochemical evidence of androgen excess
And the exclusion of:
Prolactin excess, thyroid disorder, congenital
adrenal hyperplasia & Cushings syndrome
Criteria for the diagnosis of PCO
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In 2003 a European Consensus statement
simplified this to…
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Any two of the following:
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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)
But what is PCO for the practising doctor?
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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!
Common clinical manifestations of PCO
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Obesity
Hirsutism or Acne
Menstrual irregularity
Infertility
Type 2 diabetes
Dyslipidaemia
Other manifestations of PCO
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Axillary/Groin Follicular Adenitis (Hydranitis
suppurativa)
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Premature pubarche
Bulimia
Acanthosis nigrans
Recurrent miscarriage
Frontal balding or clitoromegaly
Homosexuality (Controversial)
Cardiovascular disease
Endometrial hyperplasia and cancer
Essential Tests for possible PCO
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Ultrasound of pelvis
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Serum androgens
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Must measure free testosterone or equivalent
Fasting glucose, cholesterol & triglycerides
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More than 12 follicles 5 – 10 mm diam in one or both ovaries
NB 20% of cycling women have “polycystic ovaries”
Preferably measure insulin as well
Exclude other causes of the presenting problem
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Prolactin, Thyroid function, HydroxyPROG or
dexamethasone suppression as clinically indicated
Laboratory Manifestations of PCO
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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)
Management of the PCO Disorder
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Will depend on the principal problem…
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Hirsutism
Menstrual dysfunction
Infertility
Obesity
Diabetes and or Dyslipidaemia
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Management of Hirsutism
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Is primarily cosmetic
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Spironolactone
Cyproterone acetate (Androcur)
Combined oral contraceptive
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Shaving
Waxing
Dye or Depilation
Preferably with cyproterone acetate e.g. Diane
Other measures
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Ketoconazole
Flutamide
(not available in Australia)
Topical Eflornithine ( “
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Management of menstrual dysfunction due to PCO
Disorder
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Diet, exercise and lifestyle changes if obese
Combined oral contraceptive
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Mirena IUS is a good alternative
Cyclical or continuous progestin
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Use 3rd or 4th generation or cyproterone acetate e.g. Diane
Contraindicated if >35 years AND smoking or morbidly obese
Depot provera
An alternative for those who do not want “the pill”
There may be a role for Metformin
Endometrial resection
Hysterectomy
Management of Infertility due to PCO Disorder
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Diet, exercise and lifestyle changes if obese
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Is as effective as drugs!
Clomiphene citrate (Clomid)
In a dbRCT Letrozole was more effective than
Clomid (OR 1.44, CI 1.10 – 1.17, p=0.007)
Metformin
Ovarian drilling
FSH and HCG
IVF and ET
Management of Obesity and Dyslipidaemia with
PCO Disorder
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Diet, exercise and lifestyle changes
Metformin
A possible role for Glitazones
Sustained release Metformin may improve
compliance
So is Metformin the panacea for PCO Disorder?
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Results from combined trials:
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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
Problems in the use of Metformin for PCO
Disorder
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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
So what is the role of Metformin in PCO Disorder?
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To encourage weight loss
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To enhance the effectiveness of Clomid
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Pregnancy rates doubled and risk of miscarriage reduced
Reduces the risk of OHSS during IVF
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Non significant effect in meta analysis of RCT’s
Improves egg and embryo quality during IVF
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Non significant effect in meta analysis of RCT’s
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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