Polycystic Ovary Syndrome diagnosis & management Dr Roisin Worsley, FRACP Endocrinologist, Jean Hailes at Epworth https://jeanhailes.org.au/contents/docume nts/resources/tools PCOS is a chronic condition with manifestations that begin most commonly in adolescence with menstrual irregularity and hyperandrogenism with transition over time into problems including infertility and metabolic complications. 1
Aetiology Diagnosis 2
Oligo/anovulation Irregular cycles/anovulation (<21 or >35 days) Adolescents primary/secondary amenorrhoea 3
Biochemical or clinical hyperandrogenism Acne, hirsutism, androgenic alopecia AND/OR Raised serum testosterone Measurement of androgens Difficult to measure, can vary greatly between different labs Total testosterone + SHBG Lower SHBG = more bioavailable testosterone Lower SBHG indicative of insulin resistance Figure 2 The modified Ferriman & Gallwey scoring system for hirsutism Yildiz BO (2008) Assessment, diagnosis and treatment of a patient with hirsutism Nat Clin Pract Endocrinol Metab doi:10.1038/ncpendmet0789 How often do you shave/wax/pluck? 4
Polycystic ovaries on US Ovarian volume >10cc in absence of dominant follicle >12 follicles 2-9mm in a single ovary The Lancet 2007 370, 685-697DOI: (10.1016/S0140-6736(07)61345-2) Copyright 2007 Elsevier Ltd Terms and Conditions Exclude secondary causes Of irregular menses: thyroid disease, hyperprolactinaemia, premature menopause, Cushing s Of hyperandrogenism: non-classical adrenal hyperplasia more common in Ashkenazi Jews, Hispanics, Italians; Androgen secreting tumours rapid progression/virilization Cushing s syndrome Medication: valproate 5
Exclude secondary causes Androstendione markedly elevated in NCCAH DHEAS markedly elevated in androgen secreting adrenal tumours If concerned about Cushing s midnight salivary cortisol Non Classical Congential Adrenal Hyperplasia More common in specific groups: Ashkenazi Jews (1:27) Hispanics (1:40) Salvics (1:50) Italians (1:300) 8AM 17OH-progesterone D3-5 (Normal<6.0nmol/L, if abnormal short synacthen test w 17OHP levels) Implications for fertility treatment & risk of CAH in off-spring New M, Fertil Steril. 2006 Jul;86 Suppl 1:S2. What time of menstrual cycle should tests be done? Depends what you re testing Ideally, follicular phase Is it critical? No Small increase at T during midcycle but not clinically important If really want to exclude early menopause should ideally do FSH D3-5 6
Should the tests be done on OCP or do we need to stop and for how long? The OCP decreases T by approx 50%, increases SHBG and suppresses FSH/LH So.can check T/SHBG but if these normal doesn t exclude diagnosis. FSH/LH useless on OCP Ideally check hormones after 3 months off OCP if clinically appropriate PCOS associated risks ~ 50% obese T2DM Hypertension (?x2) Hyperlipidaemia Endometrial ca (?x3) Fatty liver Sleep apnoea Depression/anxiety Eating disorders Infertility Screening 2 yearly screening for DM/lipids Blood pressure annually Sleep apnoea further testing based on history Depression/anxiety/eating disorders Smoking/alcohol use 7
My standard initial consult History Main symptoms of concern Medications SHx relationship status, need for contraception, family plans,?special diet, exercise, smoking, alcohol, pap smears Family history DM, PCOS, infertility PHx DM/hypertension/menarche Diagnositic criteria menstrual pattern, acne/hirsutism onset/speed of change, past Ix Other symptoms weight change, mood/anxiety/ ± childhood trauma,?osa, other Physical exam Height Weight Body habitus Cushingoid facies Alopecia Acne/hirsutism lip/chin, chest, back, abdomen Acanthosis nigricans neck/axillae Buffalo hump Pigmented striae ± cliteromegaly BP My standard initial consult Arrange appropriate tests If diagnosis already clear - discuss diagnosis Jean Hailes patient info booklet Discuss concerns: fertility, what they ve read on internet, long term risks in perspective Tailor treatment to patients specific concerns Lifestyle OCP Metformin Spironolactone Management Symptoms Long term risks cardiometabolic, endometrial Fertility 8
Management - lifestyle Weight management prevent weight gain 5-10% weight loss can restore menstrual cycles Consider dietician referral Aim <5000KJ (~1200 cal); no one diet best Women with insulin resistance may find lower CHO diets easier to stick to CSIRO Total Wellbeing Diet?improve wellbeing 150min moderate/vigorous exercise/week Smoking cessation Management non-medication treatments and topical treatments Laser hair removal, esp if dark hair on light skin $$$ Eflornithine cream (Vaniqa) to prevent regrowth of hair $$$ Topical acne treatments Management the OCP The OCP Menstrual cycle regulation, endometrial protection Contraception Reduce T approx. 50%, increase SHBG Improve symptoms of androgen excess after 6-12 months?worsen insulin resistance Progestin only pill or cyclical progestin or Mirena endometrial protection Cyclical progestin: aim 4 bleeds/year 9
OCP progestin androgenicity Low notpbs Cyptoterone* (Diane) Medium/High PBS Levonorgestrel (Loette) Drospirenone* (Yaz) Norethisterone (Brevinor) Dienogest (Valette/Qlaira) Nomegestrol (Zoely) Desogestrel* (Marvelon) *increased risk of VTE c/w levonrogestrel, risks for other new progestins unknown Vinogradova et al BMJ 2015 Even OCPs with an androgenic progestin will still reduce overall T concentrations and are effective at treating hirsutism/acne Consider other risks of OCP use and individual SEs Management alternatives to the OCP Progestin only pill or Mirena endometrial protection Contraception Cyclical progestin Aim 4 bleeds/year for endometrial protection Eg MPA 10mg for 1 st -10 th of Jan/April/July/Oct Management - metformin Can result in a small degree of weight loss Can prevent weight gain associated with the OCP Prevents conversion of impaired glucose tolerance to T2DM Can restore ovulation/menses Not recommended as a 1 st line fertility treatment Start low, go slow, XR version Lowers B12 10
Management metformin XR A suggested titration approach Week 1-2: 500mg nocte w food, if tolerated increase to: Week 3-4: 1 g nocte w food, if tolerated increase to: Week 5-6: 1500mg nocte w food, if tolerated increase to: Week 7 onwards: 2g nocte w food If side effects persist/severe reduce to previously tolerated dose Can titrate more slowly if required Management anti androgens For acne/hirsutism (if OCP alone not effective after 6/12) Harmful to male fetus adequate contraception required. Stop if pregnant/breastfeeding Spironolactone 100mg-200mg daily (diuretic, menstrual irregularity, anti-hypertensive, potassium sparing) Cyproterone acetate 25-50mg for first 10 days of OCP Weight gain,?hepatotoxicity?worsen insulin resistance?depressive Management - fertility May have ovulatory cycles and not require intervention?menstrual cycle length?day 21 progesterone Weight management Early referral to fertility specialist clomid first line 11
Management - mood (covered in later talk) Many PCOS treatments can worsen mood in some women Progestins Cyproterone 12