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Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome. Christina C Ding Consultant in Obstetrics and gynaecology Subspecialist in Reproductive Medicine and Surgery. Overview. Definition (and Prevalence)- much debated Diagnostic Criteria update Management update: General: Life style changes

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Polycystic Ovarian Syndrome

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  1. Polycystic Ovarian Syndrome Christina C Ding Consultant in Obstetrics and gynaecology Subspecialist in Reproductive Medicine and Surgery

  2. Overview Definition (and Prevalence)- much debated • Diagnostic Criteria update Management update: • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific: symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  3. Definition -PCOS • Why is reaching consensus difficult? • Problems with the lack of unified definition? • New criteria in 2003

  4. Definition- PCOS Challenges in reaching a consensus • Heterogeneity in symptom and sign • For an individual, these may change over time • PCO can exist without clinical signs of the syndrome, which may become expressed overtime

  5. Range of presenting complaints • Menstrual irregularities (unopposed E2) • Anolulatory Infertility • Hyperandrogenism (Acne/Hirsutism/Alopecia) • Obesity • Metabolic Risks (DM, H/T, CVD) • Asymptomatic – incidental Scan finding of PCO

  6. DefinitionProblems without a consensual definition • Progress in Clinical Research hampered • Inconsistencies and poor delivery of clinical care

  7. DefinitionRevised 2003 Rotterdam diagnostic criteria Twoout ofthree • Oligo / Anovulation • Hyperandrogenism: clinical or biochemical • USS Features • >12 follicles of 2-9 mm in diameter , or • ovarian volume >10 cm3 in one or both ovaries Excluding: thyroid dysfunction, congenital adrenal hyperplasia, hyperprolactinaemia, androgen-secreting tumours and Cushing syndrome

  8. Prevalence • NIH criteria 1990 • 6-7% • Rotterdam consensus 2003 • 20-25% UK Caucasian • 52% UK South Asian immigrant

  9. SHBG decrease atresia Wt. increase Insulin increase Insulin receptor disorder IGFBP-I **** decrease Theca (IGF-I) Free estradiol increase Free testosterone increase High LH Low FSH hirsutism Androstenandione increase Testosterone increase Endometrial cancer Estrone increase IGFBP*** insulin like growth factor binding protein

  10. Clinical Challenges • Menstrual irregularities (unopposed E2) • Anolulatory Infertility • Hyperandrogenism (Acne/Hirsutism/Alopecia) • Obesity • Metabolic Risks (DM, H/T, CVD)

  11. Management Update • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific:symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  12. Management Update • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific: symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  13. Life Style Changes • The best diet and exercise regimens are unknown, but caloric restriction and increased physical activity are recommended. RCOG guideline

  14. Management Update • General: • Life style changes • insulin sensitising agent • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific: symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  15. Metformin • Not licensed outside DM treatment • Safe (not established in pregnancy) • Short term benefits (Wt. loss, OI, hirsutism) • No long term benefits

  16. Management Update • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific: symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  17. Cancer risks • Endometrial Cancer • Risk is 3.1 x higher(95% C I 1.1- 7.3) Coulam et al, 1983 (1270 chronic anovulation pt) • Breast Cancer • No significant increased risks Pierpoint et al., 1998; Coulam et al., 1983; Anderson et al., 1997 • Ovarian Cancer • No significant increased risks Pierpoint et al., 1998

  18. Long term risks : CVD PCOS metabolic abnormalities suggesting increased cardiovascular risk Observation Reference Triglycerides↑, HDL↓ Rajkhowa et al. (1997); Orio et al. (2004) C-reactive protein↑ Taponen et al. (2004); Boulman et al. (2004) Homocysteine↑ Carmina et al. (2005) Leucocytes↑ Orio et al. (2005) Fibrinolytic activity↓ Yildiz et al. (2002) Metabolic syndrome↑ Apridonidze et al. (2005) The ESHRE Capri Workshop Group, ‘Hormones and cardiovascular health in women’, Human Reproduction Update, 2006

  19. Long term risks: DM,H/T Follow-up studies of PCOS Authors Patients Intermediate outcomes CVD outcomes Dahlgren et al. (1992) 33 followed for 22–31 years Morediabetes and hypertension Pierpoint et al. (1998) 786 diagnosed between 1930 -79 SMR 0.9 (95% CI: 0.7, 1.2) Wild et al. (2000) 240 PCOS diagnosed before 1979 More cerebral disease and diabetes Similar CHD mortality Elting et al. (2001) 346 followed for 2–32 yearsMorediabetes and hypertension SMR, Standardized Mortality Ratio The ESHRE Capri Workshop Group, ‘Hormones and cardiovascular health in women’, Human Reproduction Update, 2006

  20. Long term risks : obstetric Meta –analysis of 15 studies involving 720 women presenting with PCOS and 4505 controls Higher risks of • Gestational DM (OR 2.94; 95% CI: 1.70–5.08) • Pregnancy-induced H/T (OR 3.67; 95% CI: 1.98–6.81) • Preterm birth (OR 1.75; 95% CI: 1.16–2.62) • Perinatal mortality (OR 3.07; 95% CI: 1.03–9.21) Hum. Reprod. Update 2006, A meta-analysis of pregnancy outcomes in women with PCOS

  21. Psychological: Quality of Life Symptoms such as acne, hirsutism, irregular menses, amenorrhoea, obesity and subfertility are a major source of psychological morbidity and can negatively affect quality of life (QoL). Systematic review: PCOS has a significant negative impact on a woman’s health-related quality of life Health-related quality of life measurement in women with polycystic ovary syndrome: a systematic review. Jones et al, Human Reproduction Update (2008)

  22. Management Update • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific:symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  23. Management Update • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific:symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  24. Antiobesity Drug • Orlistat (Xenical) • gastric/pancreatic Lipase inhibitor • Sibutramine (Reductile) • SNRI • Withdrawn since Jan 2010 due to increased heart attack and stroke risks

  25. Bariatric Surgery • Two groups: malabsorptive & restrictive procedures • Malabsorptive procedures induce decreased absorption of nutrientsby shortening the functional length of the small intestine.The created short-bowel syndrome leads to a negative energybalance and weight loss. • Restrictive operations reduce the storage capacity of the stomachand as a result early satiety arises, leading to a decreasedcaloric intake.

  26. Figure 1 Bariatric procedures. (a) Jejunoileal bypass; (b) biliopancreatic diversion; (c) biliopancreatic diversion with duodenal switch; (d) vertical banded gastroplasty; (e) laparoscopic adjustable gastric band; and (f) Roux-en-Y gastric bypass.

  27. Bariatric Surgery Benefits • Average weight loss 20–40 kg • Recovery from type 2 diabetes in 76.8% Risks • Mortality: early (<30/7) 0.1-2% • Morbidity: • VTE (0.4-3.1%) • Infection • Anastomotic leak / stenosis (20-30%)

  28. Management Update • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific: symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  29. Hyperandrogenism • Acne • Hirsutism • Male pattern hair loss • Sign of severe androgen excess (virilization)

  30. Hirsutism • 5-10% women of child bearing age • 70% PCOS • 23% idiopathic • 4.3% CAH • 0.2% A S tumour (ovarian or adrenal) • Hx: sudden onset, rapid virilization • Ix: testosterone, free testosterone. • If [testosterone] > 5nmol/L => [DHEA-S] & [androstenedione] to exclude an adrenal or ovarian tumour

  31. Hirsutism - treatment options Systemic (over 3-6 months) • COCP: less androgenic progesterone: cyproterone acetate Diannette, drospirenone Yasmin • Antiandrogens(uncommonly used) • Spironolactone (Aldactone), an aldosterone antagonist • Cyproterone acetate • Flutamide is a pure nonsteroidal antiandrogen that acts as an androgen receptor blocker. • Finasteride is a potent inhibitor of the type 2 isoenzyme of 5-á-reductase, which blocks the conversion of testosterone to 5-á-dihydrotestosterone • Corticosteroids : late onset CAH Topical • Eflornithine cream (Vaniqa) Cosmetic Direct Hair Removal: plucking, waxing, electrolysis, laser removal

  32. Management Update • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific: symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  33. Ovulation Induction: stepwise approach (RCOG) 1.Weight loss: If BMI >30 K/m2 2. Clomiphene citrate 3. CC + Metformin 4. Low dose FSH injection 5. Ovarian drilling 6. IVF

  34. Diathermy or laser Clomid resistant anovulatory PCOS Benefits Ovulation rate >70% Pregnancy rates >50% Similar pregnancy and miscarriage rates to Gonadotrophins No increase in multiple pregnancies and reduces ovarian hyperstimulation. Risks Risk of loss of ovarian tissue and thus reducing the ovarian reserve Risk of surgery ?Adhesions Laparoscopic ovarian drilling

  35. Ovarian drilling

  36. Management Update • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific: symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

  37. Mx of a/oligomenorrhea • Progesterone induced Bleeding • 3 monthly • Reduce risks of E hyperplasia and E carcinoma

  38. Overview Definition (and Prevalence)- much debated • Diagnostic Criteria update Management update: • General: • Life style changes • insulin sensitising agents • Prevention of long term health risks (CVD, Cancers, Psychological) • Specific: symptomatic control • Obesity Mx – Antiobesity drugs, Bariatric surgery • Hyperandrogenism Tx • Infertility: Anoulatory cycles • Menstrual irregularities

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