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7/27/2019 Ansc PCOS GP Update
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Polycystic Ovarian Syndrome
Gavin SacksMA BM BCh PhD MRCOG FRANZCOG CREI (UK)
Fertility Specialist IVFAustralia, Sydney
VMO Prince of Wales Private and RHW
Director of Gynaecology, St George Hospital
Conjoint Senior Lecturer UNSW
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PCOS - past and present
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PCOS - past and present
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Only 50% of women with PCOS
are overweight
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Key Learning Objectives
To be able to recognise and diagnose
PCOS
To understand the lifelong manifestationsof PCOS
To understand management options for:
longterm health hirsutism
infertility
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PCOS definition
Chronic Anovulation and Hyperandrogenism
5-10% reproductive age women
Diagnosis: 2/3 criteria *
1. Oligo-ovulation &/or anovulation
2. Hyperandrogenism (clinical or biochemical)
3. Polycystic ovaries on ultrasound (PCO)* other causes for hyperandrogenism excluded
ESHRE/ASRM PCOS Consensus Workshop May
2003
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Investigations
Serum (early follicular phase): LH/FSH
Total testosterone, Free androgen index (FAI)
Exclude other endocrinopathies*TSH, Prolactin, DHEAS, 17-OH progesterone
Pelvic ultrasound (follicular phase)
to look for PCO and endometrial abnormalities
Fasting insulin level testing is not required.Screening for metabolic syndrome in PCOS may bewarranted: Diabetes screen, lipid profile, BP check.
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Diagnosis: PCO on ultrasound
At least 1 ovary with 12+ follicles 2-
9mm &/or ovarian volume > 10mls
NB: US picture on 1 occasion sufficesfor diagnosis
ESHRE/ASRM PCOS Consensus Workshop May 2003
25% of women have PCO,
but only 5% have PCOS
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PCOS is a life-long condition
0 10 20 30 40 50 60 70
? IUGR
? Pronounced adrenarche
Menstrual irregularities
Hirsutism
Infertility, miscarriage
Gestational hypertension
Gestational diabetes
Hypercholesterolaemia
Diabetes
Hypertension
Coronary heart disease
Age (years)Long-
termhealth
Precocious
puberty
Reproductive
disorder
Metabolic syndrome
Cancer (uterine; ?breast)
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Long-term health risks
Reproductive: Endometrial Cancer
Metabolic: Diabetes, Dyslipidaemias, Hypertension, Obesity
Unproven:
Cardiovascular Disease
Breast cancer
Established:
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Cancer risk
Endometrial
Protection from withdrawal bleed at least every 3/12
Breast Weak association (RR 1.2)
Women often concerned and try to avoid the pill
(NB. The pill protects against ovarian Ca)
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Metabolic problems
Hypertension
Dyslipidaemia
TC, LDL-C, TGs
HDL-C
Future diabetes
? Cardiovascular disease (CVD)
coronary disease
myocardial infarction
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The pill versus metformin
OCP
Cycle control
Contraceptive Side effects
Contraindications
Reduce ovarian
cancer
Metformin
Induce ovulation 70%
No contraception Well tolerated
No contraindications
?? Only use if proven
hyperinsulinaemia
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OCP - metabolic concerns
glucose tolerance
insulin resistance
lipid levels
Diabetes
Cardiovascular disease
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Insulin Resistance
Insulin resistance (IR):
is a prominentfeature in both obese (65-90%) and lean(25-45%) women with PCOS
is unique to PCOS as occurs independently to obesity,
but is aggravated by obesity
(Franks S 1989; Dunaif A 1994)
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PCOS and glucose intolerance
Increased prevalence of glucose intolerance
(35%) and type 2 diabetes (10%)
Also increased in non-obese PCOS (10%, 1.5%)
Increased risk (x3-7) of developing type 2 diabetes
PCOS women develop glucose intolerance at an
early age (3rd-4th decade)
PCO is risk factor for gestational diabetes
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The case for metformin
Women with PCOS: over 6 years:
9% develop impaired glucose tolerance
8% develop diabetes
Metformin can reduce progression todiabetes by 31% in non-PCOS populations
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Metformin
Direct intracellular effects to reduce hepaticgluconeogenesis, improve glucose metabolism
Target dose: 1500 2550mg daily with meals
Most common side effects are GI (diarrhea,
nausea/vomiting, flatulence, indigestion, abdodiscomfort)
Rare problem of lactic acidosis: never been
reported in PCOS
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Metformin in PCOS
Lifestyle 1st line treatment if overweight
Some advocate lifelong metformin from puberty
Currently no long-term data on metformin use
Uncertain advantage adding metformin to OCP
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OCP versus metformin: RCTs
OCP more effective in improving menstrual pattern
OCP more effective in reducing serum androgens
No difference between OCP & metformin in effect onhirsutism or acne
No adverse metabolic risk with the use of the OCPcompared to metformin for both clinical and surrogate
metabolic outcomes.
Possible benefit of adding metformin to OCP (improvedhirsutism)
Cochrane review: Costello et al 2007
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Hirsutism
Cosmetic measures
Waxing, shaving, laser
Oral contraceptive
Any (often diane/ yasmin)
Metformin Need contraception
Anti-androgens
Spironolactone (very weak)
Cyproterone acetate (need to use 50mg for effect)5-alpha-reductase inhibitors
Finasteride
Effective but potentially teratogenic
Must counsel carefully and use oral contraceptive
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Infertility: anovulatory
Weight loss if BMI >25 (diet/ exercise)
Clomid (50 - 150mg) versus metformin
Clomid and metformin combined
FSH stimulation
Ovarian drilling
IVF
IVM
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Clomiphene citrate
Used since 1960s
Safe to use for 9-12 months continuously
Oestrogen receptor antagonist: boostnatural FSH release
Can have detrimental effect on
endometrium
Try tamoxifen alternative
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FSH stimulation (OI + IUI)
Low doses
Need cycle monitoring
Pregnancy rates 15-20%
Multiple rate 20-25%
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Ovarian drilling
As effective as OI
natural conception
No multiples
Laparoscopy
Risk of adhesions (unproven)
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IVF
Best way to achieve singleton pregnancy inPCOS infertility
Main risk is OHSS (ovarian hyperstimulation
syndrome) Low doses of stimulation
Careful and frequent monitoring
Co-treatment with metformin unproven benefit:
ongoing trial at IVFA Blastocyst transfer
Sometimes freeze all embryos
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IVM (in vitro maturation)
Collect immature eggs
Culture in vitro
Fertilise and transferembryos
Few centres worldwide Recently reported 1st success in UK
Twins as 2 embryos transferred
400 babies born (versus >2 million IVF)
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Miscarriage
40% of women with recurrent miscarriagehave PCO (general population 25%)
Miscarriage rate increased in women withPCO
High insulin levels can affect theendometrium and implantation
Metformin has no known teratogenic effect
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PCOS, miscarriage and metformin
Glueck 01 reduced miscarriage rate from 73% to 10% (n=22)
Jakubowicz 02 reduced miscarriage rate from 42% (n=31
untreated) to 8.8% (n=37 treated)
Thatcher 06 decreased miscarriage rate with no increased
anomalies (n=188; 237 pregnancies)
RCTs awaited (NB. RCT Suppression LH not effective)
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Pregnancy
Outcomes:
Maternal: Gestational Diabetes (OR 2.94)
Pregnancy induced hypertension (OR 3.67) Cesarean sections
Acne
Neonatal: Admission to ICU
Premature delivery (OR 1.75)
Metformin still considered experimental
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Conclusions
1. PCOS is common.
2. Always focus on presenting problem, but also
educate patients about the long-term sequellae.
3. Life-style modification is a very effective treatment
option in PCOS.
4. Do not be scared of using the OCP.
5. Ongoing trials for metformin in IVF and
miscarriage.