Managing pcos in general practice
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Managing PCOS in General Practice. John Eden UNSW, RHW. Conflict of interest statement. In the last 10 years, I have been a paid scientific adviser for

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Managing PCOS in General Practice

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Managing PCOS in General Practice

John Eden

UNSW, RHW


Conflict of interest statement

  • In the last 10 years, I have been a paid scientific adviser for

    • Solvay Pharmaceuticals, Wyeth-Ayerst, Organon P/L, Novartis P/L, Novo-Nordisk, Arkopharma P/L, Roche Pharmaceuticals Lawley Pharmaceuticals, CSL, and AstraZenica P/L.

  • My research unit performs trials for the pharma, food & supplement industries


WHRIA and Country gynaecology services

  • What is WHRIA?

    • Clinical services

    • Information services (with UNSW). Example - PCOS awareness campaign.

    • Research (Barbara Gross Research Unit at RHW)

  • Country outreach clinics (with RDN)

    • Bourke, Moree

    • GPs – Other areas that need gynae services

    • Specialists who want to help

  • Contact me at [email protected]


Definition of hirsutism

  • Excessive terminal hair (black & coarse) that appears in a male pattern in women

  • Patient and doctor attitudes towards hirsutism can be quite different

  • Affects up to 15% of women

  • Obviously there are racial differences


Is Hirsutism hormonal?

  • Most hirsute women have PCO (90%, Adams, 1986) & the severity correlates some-what with serum androgens & 5a-reductase activity

  • Most women with acne have PCO (Bunker, 1989; severity poorly correlates with androgens)

  • PCO is found in 26% with amenorrhoea & 87% with oligomenorrhoea (Adams, 1986; severity correlates with serum androgens)


Differential Diagnosis

  • PCOS – the vast majority

  • Other medical causes

    • Cushing’s syndrome

    • Adrenal, ovarian tumours

    • Self-medication (testosterone, anabolic steroids)

  • Idiopathic


Polycystic ovaries

A Morphologic diagnosis

  • ‘Presence of 12 or more follicles in each

  • ovary measuring 2-9mm in diameter &/or increased ovarian volume (>10ml)’

    One in four women have PCO on scan


PCO syndrome definition

Revised 2003 Rotterdam ESHRE/ASRM

(2 out of 3) –

  • Irregular periods

  • Evidence of raised male hormone levels

  • PCO & exclusion of other causes


Genetic

Intra-uterine

Nutritional

Hormonal

Fat

Insulin

Skin sensitivity

Disordered ovulation

Hirsutism, acne


Probably all women with hirsutism should have some tests

  • LH, FSH, TSH, PRL, Total T, SHBG, DHEAS, 17OHP.

  • Fasting lipids, glucose. Maybe GTT (& insulins)

  • Scan – doesn’t add a lot

  • PCOS: Usually at least one of LH, T or SHBG is abnormal


Red Flags

  • Always repeat a grossly abnormal result

  • Congenital Adrenal Hyperplasia: markedly raised 17OHP (do Synacthen test)

  • Very high T (>6nmol/l) or DHEAS (twice the upper limit of normal): think tumour

  • Abnormal GTT

  • Raised triglycerides (may be a sign of severe IR)


Insulin Resistance

IR occurs in 30-60% of women with PCOS (Dunaif, 1992)

IR is a post-receptor phenomenon, multifactorial & is mostly sited in the fat, muscle & liver, but the ovaries remain spared.

Raised serum insulin levels stimulate ovarian androgen production & decrease hepatic SHBG production.

IR is associated with adverse CVS surrogates (raised lipids, especially triglycerides & hypertension)

Insulin sensitizers (metformin, the glizones) improve the androgenic profile & may induce ovulation.


Management options for the hirsute woman


Hair removal

  • Waxes, creams

  • Shaving

  • Electrolysis

  • Laser


Insulin Resistance

  • Low GI diet

  • Exercise

  • Metformin

  • Other weight loss strategies

    • Weight loss drinks

    • Drugs

    • Weight loss surgery


Metformin

  • Safe when used to treat gestational diabetes (MiG trial, N= 751, N Engl J Med 2008; 358: 2003-15)

  • Not associated with increased fetal abnormalities when used in first trimester (meta-analysis, 172 treated, 235 controls, Fert Ster Vol. 86, No. 3, September 2006)

  • Helps restore the cycle, & lowers risk of diabetes but doesn’t help hirsutism much


Statins

  • Many women with PCOS have adverse CVS markers which can be reversed with a statin

  • Statins inhibit proliferation and steroidogenesis of ovarian theca–interstitial cells in culture

  • Pawelczyk recently presented data on 60 women with PCOS randomised to simvastatin 20mg or metformin 850mg bd or both (Society for Reproductive Endocrinology and Infertility meeting 2008)


Results

  • Note

  • These data are very preliminary

  • Statins have been linked to birth defects


Menstrual problems

  • delayed first period

  • infrequent periods

  • heavy bleeding

  • continual bleeding

    Contraception requirements


Tranexamic acid

  • Anti-fibrinolytic

  • Safe, sold over the counter in Europe.

  • Dosage: 1g 3-4 times a day, day 1-5

  • Very effective for heavy periods – usually more than halves the flow. Superior to OCP.

  • Side effects: nausea with doses >6g/day


Contraceptive Pill

  • Takes months to help hirsutism.

  • Effective for heavy periods. Can skip periods. Contraceptive. Superior to metformin for skin problems

  • Side effects: watch triglycerides & BP (oestrogen) & weight gain with CPA. Might aggravate IR. ‘PMT’ with progestin.


Progestins

  • Cyclical vs continuous

  • Uses: to stop a heavy period. Every 2m to prevent uterine lining build up

  • Side effects: ‘PMT’ (1/8); some have an adverse effect on IR. Dydrogesterone has no measurable metabolic effect.


Spironolactone

  • Need at least 100mg for anti-androgen effect

  • Used for skin problems, but often shortens the cycle.

  • Takes months to work

  • Side effects: diuretic


Eflornithine Cream

  • Eflornithine is an irreversible inhibitor of ornithine decarboxylase which in turn slows hair growth. Works in 2/3 in 4-8 weeks

  • Use sparingly. Tube lasts 3-4 months

  • Side effects: ‘tingling’


Clinical Trials

  • Two double-blind, randomised, parallel, vehicle-controlled studies performed with 596 women diagnosed with UFH were carried out

  • Subjects were randomised to receive Eflornithine or vehicle cream, applied topically twice daily for 24 weeks

  • By 8-weeks the active treatment had significantly better results than placebo. Eflornithine helped around 2/3 women


Clinical Trials

  • Side effects reported occurred at similar frequencies in Eflornithine and control groups, with most being skin-related. Side effects are primarily mild and resolve without medical treatment or discontinuation. It can sometimes aggravate acne.

  • Eflornithine has not been associated with phototoxic or photosensitisation reactions

  • A trial combining Eflornthine with laser hair removal, showed the women on active treatment needed fewer laser treatments


Levonorgestrel-IUD

  • Mechanism of action: progestin containing IUD. Safe, cheap, lasts 5 years. Very effective for heavy periods.

  • Contraceptive, reversible.

  • Side effects: Might need a GA to get it in.

  • Spotting for up to 3m. Can fall out. Risk of PID is ½ normal because of progestin’s effect on cervical mucus. Very little systemic effect.


Take Home Messages

  • PCO is common (1 in 4) & women with PCO & >6 periods a year are normal.

  • PCOS = PCO and symptoms

  • Around ½ women with PCOS & irregular periods, have IR

  • Measure lipids & fasting glucose in everyone (even the young)

  • For women with PCOS think about doing a 75g GTT (insulin & glucose levels)


Take Home Messages

  • Dietary recommendations: low GI, low fat diet

  • OCP – may increase triglyceride levels, but OCP better than metformin for acne & hirsutism.

  • Anti-androgens & Eflornithine lotion for hirsutism or acne

  • Metformin may be useful to help IR, aids weight loss & may induce ovulation. Doesn’t help hirsutism much.

  • Consider weight loss surgery for severely obese patients


Take Home Messages

  • Tranexamic acid will control heavy periods if the uterus is normal.

  • The Levonorgestrel-IUD is an excellent option for many women with PCOS as it controls heavy periods & prevents uterine cancer; without metabolic effects. It is cheap, lasts 5 years and on removal, fertility returns immediately.


Cases


Ms TG, 14y young woman with irregular heavy periods with flooding. She has about 3-4 periods a year.

Tests show she has PCOS, but no evidence of metabolic syndrome.

She is anaemic with low iron studies.

Ultrasound scan shows an 8cm normal uterus


Tranexamic acid

Progestins

OCP

Metformin


A 25y woman having 1-2 periods per year.

BP 150/90; BMI 32. General exam nad, except acanthosis both axillae.

Cholesterol 6; TG 4.5

Fasting glucose 5.8

Fasting insulin 50u/l


Treat IR

Tranexamic acid

Cyclical dydrogesterone

Levonorgestrel-IUD

OCP


28 year old with PCOS & heavy periods.

She also has acne & excess hair.

Normal BP and no evidence of metabolic syndrome


OCP (& spironolactone)

Eflornithine cream

Hair removal

Levonorgestrel-IUD

Tranexamic acid

Progestins


28 year old woman with 12m infertility. She has 6 periods a year. Tests confirm PCOS. BMI 31.


Check other fertility factors

Weight loss

Metformin or clomiphene

Monitor ovulation when cycles regular

(BBT charts, LH kits)


58 year old post-menopausal woman with excess facial hair. Most is light, ‘peach-fuzz,’ and some dark course terminal hair. She is not on HRT.

Serum androgens normal.


Eflornithine cream

Hair removal

Spironolactone


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