Managing PCOS in General Practice

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Managing PCOS in General Practice
John Eden UNSW, RHW
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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

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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 info_at_WHRIA.com.au

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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

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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)

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Differential Diagnosis

• PCOS the vast majority
• Other medical causes
• Cushings syndrome
• Adrenal, ovarian tumours
• Self-medication (testosterone, anabolic steroids)
• Idiopathic

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Polycystic ovaries

• A Morphologic diagnosis
• Presence of 12 or more follicles in each
• ovary measuring 2-9mm in diameter /or increased
  ovarian volume (gt10ml)
• One in four women have PCO on scan

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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

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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 doesnt add a lot
• PCOS Usually at least one of LH, T or SHBG is
  abnormal

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Red Flags

• Always repeat a grossly abnormal result
• Congenital Adrenal Hyperplasia markedly raised
  17OHP (do Synacthen test)
• Very high T (gt6nmol/l) or DHEAS (twice the upper
  limit of normal) think tumour
• Abnormal GTT
• Raised triglycerides (may be a sign of severe IR)

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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.

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Management options for the hirsute woman
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Hair removal

• Waxes, creams
• Shaving
• Electrolysis
• Laser

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Insulin Resistance

• Low GI diet
• Exercise
• Metformin
• Other weight loss strategies
• Weight loss drinks
• Drugs
• Weight loss surgery

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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 doesnt help hirsutism much

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Statins

• Many women with PCOS have adverse CVS markers
  which can be reversed with a statin
• Statins inhibit proliferation and steroidogenesis
  of ovarian thecainterstitial 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)

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Results
Signif differences simvastatin metformin both
Increase in menses BMI decrease 89 2.2 32 4.3 68 5.8

• Note
• These data are very preliminary
• Statins have been linked to birth defects

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Menstrual problems

• delayed first period
• infrequent periods
• heavy bleeding
• continual bleeding
• Contraception requirements

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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 gt6g/day

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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.

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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.

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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

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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

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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

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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

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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 progestins effect on
  cervical mucus. Very little systemic effect.

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Take Home Messages

• PCO is common (1 in 4) women with PCO gt6
  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)

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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. Doesnt help
  hirsutism much.
• Consider weight loss surgery for severely obese
  patients

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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.

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Cases
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• 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

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• Tranexamic acid
• Progestins
• OCP
• Metformin

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• 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

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• Treat IR
• Tranexamic acid
• Cyclical dydrogesterone
• Levonorgestrel-IUD
• OCP

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• 28 year old with PCOS heavy periods.
• She also has acne excess hair.
• Normal BP and no evidence of metabolic syndrome

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• OCP ( spironolactone)
• Eflornithine cream
• Hair removal
• Levonorgestrel-IUD
• Tranexamic acid
• Progestins

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

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• Check other fertility factors
• Weight loss
• Metformin or clomiphene
• Monitor ovulation when cycles regular
• (BBT charts, LH kits)

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• 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.

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• Eflornithine cream
• Hair removal
• Spironolactone