Polycystic Ovarian Syndrome

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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 - PowerPoint PPT Presentation

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  • Polycystic Ovarian SyndromeChristina C DingConsultant in Obstetrics and gynaecologySubspecialist in Reproductive Medicine and Surgery

  • OverviewDefinition (and Prevalence)- much debatedDiagnostic Criteria update

    Management update:General:Life style changesinsulin sensitising agentsPrevention of long term health risks (CVD, Cancers, Psychological)Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

  • Definition -PCOSWhy is reaching consensus difficult?

    Problems with the lack of unified definition?

    New criteria in 2003

  • Definition- PCOS Challenges in reaching a consensusHeterogeneity 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

  • Range of presenting complaintsMenstrual irregularities (unopposed E2)

    Anolulatory Infertility

    Hyperandrogenism (Acne/Hirsutism/Alopecia)

    Obesity

    Metabolic Risks (DM, H/T, CVD)

    Asymptomatic incidental Scan finding of PCO

  • DefinitionProblems without a consensual definitionProgress in Clinical Research hampered

    Inconsistencies and poor delivery of clinical care

  • Definition Revised 2003 Rotterdam diagnostic criteriaTwo out of three

    Oligo / Anovulation

    Hyperandrogenism: clinical or biochemical

    USS Features>12 follicles of 2-9 mm in diameter , orovarian volume >10 cm3 in one or both ovaries

    Excluding: thyroid dysfunction, congenital adrenal hyperplasia, hyperprolactinaemia, androgen-secreting tumours and Cushing syndrome

  • PrevalenceNIH criteria 1990 6-7%

    Rotterdam consensus 200320-25% UK Caucasian52% UK South Asian immigrant

  • Wt. increaseInsulin receptor disorderInsulin increaseFree estradiolincreaseHigh LHLow FSHFree testosteroneincreaseAndrostenandione increaseSHBG decreaseatresiaTheca (IGF-I)Endometrial cancerTestosteroneincreaseEstroneincreasehirsutismIGFBP-I **** decreaseIGFBP*** insulin like growth factor binding protein

  • Clinical ChallengesMenstrual irregularities (unopposed E2)

    Anolulatory Infertility

    Hyperandrogenism (Acne/Hirsutism/Alopecia)

    Obesity

    Metabolic Risks (DM, H/T, CVD)

  • Management UpdateGeneral:Life style changesinsulin sensitising agentsPrevention of long term health risks (CVD, Cancers, Psychological)

    Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

  • Management UpdateGeneral:Life style changesinsulin sensitising agentsPrevention of long term health risks (CVD, Cancers, Psychological)

    Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

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

  • Management UpdateGeneral:Life style changesinsulin sensitising agentPrevention of long term health risks (CVD, Cancers, Psychological)

    Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

  • MetforminNot licensed outside DM treatmentSafe (not established in pregnancy)Short term benefits (Wt. loss, OI, hirsutism)No long term benefits

  • Management UpdateGeneral:Life style changesinsulin sensitising agentsPrevention of long term health risks (CVD, Cancers, Psychological)

    Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

  • Cancer risksEndometrial Cancer Risk is 3.1 x higher(95% C I 1.1- 7.3)Coulam et al, 1983 (1270 chronic anovulation pt)Breast CancerNo significant increased risksPierpoint et al., 1998; Coulam et al., 1983; Anderson et al., 1997Ovarian CancerNo significant increased risks Pierpoint et al., 1998

  • Long term risks : CVD PCOS metabolic abnormalities suggesting increased cardiovascular risk

    ObservationReference

    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

  • Long term risks: DM,H/TFollow-up studies of PCOS

    AuthorsPatients Intermediate outcomes CVD outcomes

    Dahlgren et al. (1992) 33 followed for 2231 years More diabetes and hypertensionPierpoint 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 mortalityElting et al. (2001) 346 followed for 232 years More diabetes and hypertension

    SMR, Standardized Mortality Ratio

    The ESHRE Capri Workshop Group, Hormones and cardiovascular health in women, Human Reproduction Update, 2006

  • Long term risks : obstetricMeta analysis of 15 studies involving 720 women presenting with PCOS and 4505 controls

    Higher risks of Gestational DM (OR 2.94; 95% CI: 1.705.08)Pregnancy-induced H/T (OR 3.67; 95% CI: 1.986.81)Preterm birth (OR 1.75; 95% CI: 1.162.62) Perinatal mortality (OR 3.07; 95% CI: 1.039.21)

    Hum. Reprod. Update 2006, A meta-analysis of pregnancy outcomes in women with PCOS

  • 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 womans 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)

  • Management UpdateGeneral:Life style changesinsulin sensitising agentsPrevention of long term health risks (CVD, Cancers, Psychological)

    Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

  • Management UpdateGeneral:Life style changesinsulin sensitising agentsPrevention of long term health risks (CVD, Cancers, Psychological)

    Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

  • Antiobesity Drug

    Orlistat (Xenical)gastric/pancreatic Lipase inhibitor

    Sibutramine (Reductile)SNRIWithdrawn since Jan 2010 due to increased heart attack and stroke risks

  • Bariatric SurgeryTwo groups: malabsorptive & restrictive procedures Malabsorptive procedures induce decreased absorption of nutrients by shortening the functional length of the small intestine. The created short-bowel syndrome leads to a negative energy balance and weight loss. Restrictive operations reduce the storage capacity of the stomach and as a result early satiety arises, leading to a decreased caloric intake.

  • 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.

  • Bariatric SurgeryBenefitsAverage weight loss 2040 kg Recovery from type 2 diabetes in 76.8%RisksMortality: early (
  • Management UpdateGeneral:Life style changesinsulin sensitising agentsPrevention of long term health risks (CVD, Cancers, Psychological)

    Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

  • HyperandrogenismAcne

    Hirsutism

    Male pattern hair lossSign of severe androgen excess (virilization)

  • Hirsutism5-10% women of child bearing age70% PCOS23% idiopathic4.3% CAH0.2% 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

  • Hirsutism - treatment optionsSystemic (over 3-6 months)COCP: less androgenic progesterone: cyproterone acetate Diannette , drospirenone YasminAntiandrogens (uncommonly used) Spironolactone (Aldactone), an aldosterone antagonistCyproterone 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--reductase, which blocks the conversion of testosterone to 5--dihydrotestosteroneCorticosteroids : late onset CAHTopicalEflornithine cream (Vaniqa)Cosmetic Direct Hair Removal: plucking, waxing, electrolysis, laser removal

  • Management UpdateGeneral:Life style changesinsulin sensitising agentsPrevention of long term health risks (CVD, Cancers, Psychological)

    Specific: symptomatic controlObesity Mx Antiobesity drugs, Bariatric surgeryHyperandrogenism Tx Infertility: Anoulatory cyclesMenstrual irregularities

  • Ovulation Induction: stepwise approach (RCOG)1. Weight loss: If BMI >30 K/m22. Clomiphene citrate 3. CC + Metformin4. Low dose FSH injection5. Ovarian drilling 6. IVF

  • Laparoscopic ovarian drillingDiathermy o

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