Year 5 Medicine

1. Year 5 Medicine Polycystic Ovary Syndrome and Hirsutism Stella Milsom

2. Overview • diagnosis of PCOS-new Rotterham Consensus • symptoms of PCOS • future health risks associated with PCOS • relevant investigation of woman with likely symptoms • management of hirsutism related to PCOS

3. What is polycystic ovary syndrome? • syndrome of ovarian hyperandrogenisation • associated symptoms of androgen excess • anovulation leads to menstrual irregularity • most common gynaecological condition affecting women of childbearing age • also associated with the metabolic syndrome

5. Pathogenesis of PCOS LH  insulin/IGF1  cytochrome P450   ovarian androgen production  disturbed folliculogenesis obesity

6. Diagnosis of polycystic ovary syndrome symptoms of androgen excess • irregular menses • acne, hirsutism biochemical androgen excess •  total / free testosterone,  androstenedione,  LH pelvic ultrasound • 1 or both ovaries enlarged, >12 peripheral follicles

7. Anovulation in PCOS presents as: absence of periods infrequent periods ( > 35 day cycle) dysfunctional uterine bleeding occasionally regular periods risk of endometrial cancer

11. Biochemistry in PCOS Raised LH or LH:FSH ratio One or more androgen levels raised testosterone androstendione DHEAS

12. Normal ovaries volume < 8 cm3 scattered follicles Polycystic Ovaries Generally >8cm3 peripheral distribution of follicles increased stroma Polycystic Ovaries

14. 2004 Consensus PCOS Definition 2 out of the following 3 features anovulation clinical and/or biochemical evidence of androgen excess polycystic ovaries on ultrasound: 1 or more ovaries ≥10mls in size and ≥12 follicles Human Reproduction, 2004

15. PCOS • PCOS is also associated with a characteristic metabolic syndrome that includes: • insulin resistance • dyslipidemia • hypertension • These features are linked with increased risks of type 2 diabetes and possibility of premature cardiovascular disease

16. Metabolic abnormalities in PCOS due to insulin resistance • impaired GTT 40% • Diabetes – 5x more likely than weight matched controls OGTT vs FG • gestational diabetes increased risk • dyslipidemia ¯HDL LDL TG  potential cardiovascular risk

17. Associations of PCO with clinical conditions PCO present in • 75% cases of anovulatory infertility (Adams 1986, Hull 1987) • 87% cases of oligomenorrhoea (Adams 1986) • 80% cases of hirsutism and regular menses (Adams 1986, Hull 1987) • 83% women presenting with acne to dermatology clinic (Bunker 1989) • 30-40% women with amenorrhoea (Adams 1986)

18. What tests are useful? • androgens, FSH, LH, estradiol • prolactin, thyroid function, pregnancy test (causes of secondary amenorrhea) • ultrasound pelvis

19. What tests are useful? remember to exclude secondary causes of PCOS • androgen secreting tumour • acromegaly • non classical CAH

20. Management of PCOS • symptom orientated • long term risk reduction

21. Management of PCOS- Current Symptoms • determine which predominates-infertility or androgen excess • then consider antiandrogen versus ovulation induction therapy • consider state of endometrium • first line medical management from diagnosis to reproduction most likely be OCP

22. Hirsutism and PCOS defined as coarse terminal hair in a male distribution do not confuse with lanugo hair assessed by the Ferriman-Galwey score does not always correlate with androgen levels

23. Management of androgen excess symptoms in PCOS symptoms include: hirsutism acne androgenic alopecia

24. Management of androgen excess symptoms in PCOS First line treatment for mild hirsutism weight loss and exercise oral contraceptive (Estelle and Yasmin) metformin

25. Effect of lifestyle in hirsute PCOS • weight gain causes an increase in insulin resistance and androgen production in PCOS women • antiandrogen therapy is less efficacious • modest weight loss and increase in exercise e.g. 5-10% weight loss will often improve hirsutism by reducing androgen production

26. OCP and hirsutism • first line treatment for hirsutes (manages endometrium and contraception also) • synthetic E2 suppresses gonadotropin driven androgen production • increase in SHBG decreases bioavailable T to hair follicle • addition of low dose CPA (Estelle) provides antiandrogenic progesterone

27. Metformin and hirsutism useful alternative to OCP in woman with hirsutism who also desiresfertility common to have gut side effects commence slowly, work up to 1500mg/day moniter with liver and renal function ( occasional hepatotoxicity, theoretical risk of lactic acidosis)

28. Metformin and hirsutism In both lean and overweight women with PCO • improves insulin sensitivity and lipids • decreases hyperandrogenism • increases frequency of ovulation (40-70%) compared to placebo

29. Management of androgen excess symptoms in PCOS Treatment of more severe hirsutism (refer) OCP plus additional antiandrogen therapy: spironolactone 200mg/day cyproterone in reverse sequential regime (specialist) flutamide 250mg/day (specialist) finasteride unfunded and less effective for the future: vaniqa cream (ornithine decarboxylase inhibitor)

30. Combination antiandrogen therapy • use in conjunction with OCP • specialist prescription • require monitoring (liver function) • used in more severe hirsutism or unresponsive women • course up to 36 months • require contraception • 6 months before effect but may improve up to 2 years after initiating therapy (50% reduction in FG score)

31. Management of PCOS-longer term • consider OCP, metformin, progestins, antiandrogens, ovulation induction, lipid lowering agents, antihypertensives as necessary • surveillance for diabetes, hypertension and dyslipidemia especially if positive family history and overweight • monitor endometrium • active weight loss and exercise programme