ansc pcos gp update

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.

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