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Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com
 

Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com

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Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com

Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com

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    Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com Polikistik Over Sendromu - PCOS - www.jinekolojivegebelik.com Presentation Transcript

    • PCOS Dr. Mridula A Benjamin Dept of Obs and Gyn RIPAS Hospital, Brunei
    • Introduction
      • Heterogenous problem
      • Commonest hormonal disturbance
      • Ovarian expression of metabolic syndrome
      • Long term consequences - strategies to screen
      • Stein Leventhal syndrome
    • ASRM/ ESHRE
      • Rotterdam: May 2003
      • Two of three: Oligomenorrhoea & or anovulation
      • Hyperandrogenism; Clinical/biochemical
      • PCO on USG; 12 or more, 2-9mm,10cm 3
      • Single PCO
      • The follicle distribution & increase in stromal echogenecity & volume should be omitted
      • Chronic anovulation & hyperandrogenism in absence of other endocrine disorders
      • January issue of Fertility & Sterility J, 2004
    • Ultrasound
      • Polycystic ovaries
        • Bilateral
        • Multiple cysts
        • Cyst diam <2-9mm
        • Stroma increased
      • Multicystic ovaries
        • Bilateral
        • Multiple cysts
        • Cyst diam > 6-10 mm
        • Stroma not increased
    •  
    •  
    •  
    • Gross appearance of ovaries
      • Enlarged bilaterally and have a smooth thickened avascular capsule
      • On cut section, subcapsular follicles in various stages of atresia are seen
      • Microscopically luteinizing theca cells are seen
    •  
    •  
      • The best biochemical markers of hyperandrogenism are
      • free testosterone levels or free androgen index
      • Not all patients with PCOS have elevated circulating androgen levels
      • Routine measurement of androstenedione cannot be recommended
      • DHEAS is raised in small fraction of patient with PCOS levels
      • LH levels are elevated in 60% women with PCOS
      • LH/FSH ratios can be elevated in up to 95% of women with PCOS if women with recent ovulation are excluded
      • LH levels are not necessary for clinical diagnosis of PCOS
      • Implications?? High miscarriage / low fertility
      • The chances of ovulation or pregnancy rates using CC or HMG are unaffected
      • PCOS should be excluded from other disorders in which hirsutism and menstrual irregularities are prominent
      • Congenital adrenal hyperplasia
      • Cushing's syndrome
      • Androgen-secreting tumors
      • In oligo/anovulation:
      • E2 & FSH to exclude hypogonadotrophic hypogonadism (central origin of ovarian dysfunction)
      • Thyroid disorders in PCOS patients are not more common than in other young women, and TSH is unnecessary
      • In hyperandrogenic females: Prolactin
    • Metabolic syndrome 3 of the following 1. Waist circumference >88cm 2. Triglycerides >150 mg/dl 3. HDL <50 mg/dl 4. Blood pressure > 130/85 5. Fasting Blood glucose 110-126 &/or 2-h glucose 140-199 mg/dl
    • Prevalence
      • PCO on ultrasound - 20%-33%
      • Oligomenorrhea - 4 – 21 %
      • Oligomenorrhea + hyperandrogenism - 3.5 – 9 %
    • Pathogenesis (etiology?)
      • Hypersecretion of adrenal androgens?
      • Hypersecretion of ovarian androgens?
      • A genetic disorder with an autosomal dominant mode of inheritance?
      • A multifactorial genetic disorder?
    • Cholesterol Pregnenolone Progesterone 17 OH-Pregnenolone 17 OH-Progesterone DHEA Androstenandion 17-20 Lyase 17 hydroxylase Theca cell Estrone estradiol Granulosa cell FSH LH OVARIAN STEROIDOGENESIS T
    • Obesity Insulin Free testosterone SHBG IGF-1 5-alfa reductase activity is stimulated IGF*** insulin like growth factor
    • Obesity and insulin resistance
      • Diminished biological response to insulin
      • In both obese and non obese
      • In 40%
      • More in obese and oligomenorrhoeic
      • Euglycaemia at expense of hyperinsulinaemia
      • Obesity more of central -35-60%
    • Wt. increase Insulin receptor disorder Insulin increase Free estradiol increase High LH Low FSH Free testosterone increase Androstenandione increase SHBG decrease atresia Theca (IGF-I) Endometrial cancer Testosterone increase Estrone increase hirsutism IGFBP-I **** decrease IGFBP*** insulin like growth factor binding protein
    • Presentation
      • Amenorrhea-
      • Oligomenorrhea
      • Infertility
      • Hirsutism
      • Obesity
      • Acne Vulgaris
      • Asymptomatic
    •  
    • Laboratory studies
      • Increased androgen levels in blood (testosterone and androstendione)
      • Increased LH, exaggerated surge
      • Increased fasting insulin
      • Increased prolactin
      • Increased estradiol and estrone levels
      • Decreased SHBG levels
    • Long term risks in PCOS
      • Definite
      • Type 2 diabetes(15%), IGT( 18-20%)
      • Dyslipidemia (Hypercholesterolemia with diminished HDL2 and increased LDL)
      • Endometrial cancer (OR 3.1 95% CI 1.1 -7.3)
      • Possible
      • Hypertension
      • Cardiovascular disease
      • Gestational diabetes mellitus
      • Pregnancy-induced hypertension
      • Ovarian cancer
      • Unlikely
      • Breast cancer
      Long term consequences
    • Management
      • Symptom oriented
      • Diet & exercise
      • Wt. loss
      • Improves both symptoms & endocrine profile
      • BMI >30kg/ m 2
      • Keep CHO content down, avoid fatty food
      • Obesity clinics
    • Contd
      • Menstrual irregularities
      • OCP- Yasmin, Dianette
      • ET >10mm(oligo), >15mm(amen)-Withdrawal bleed
      • Fails - Endometrial sampling
    • STEPWISE APPROACH FOR OVULATION INDUCTION IN PCOS (ACOG,2002 ) 1. Weight loss: If BMI >30 K/m 2 2. Clomiphene citrate 3. CC + corticosteroids if DHES > 2ug/ml 4. CC + Metformin 5. Low dose FSH injection 6. Low dose FSH injection + Metformin 7. Ovarian drilling 8. IVF
    •  
    • Mx of Hirsutism
      • Cosmetic
      • Medical- 6-7 months
      • Cyproterone acetate+ EE, Spironolactone
      • Reliable contraception
      • Flutamide & Finasteride - Rare
    • Reproductive Endocrinologist
      • S.testosterone > 5nmol/L
      • Rapid onset hirsutism
      • IGT/ Type2 DM
      • Refractory symptoms
      • Amen. > 6 months
      • Subfertility
    • Guidelines (RCOG, May 2003)
      • 1-Patients presenting with PCOS particularly if they are obese, should be offered measurement of fasting blood glucose and urine analysis for glycosuria. Abnormal results should be investigated by a glucose tolerance test
      • Such patients are at increased risk of developing type II diabetes (Evidence level IIb[C])
      • 2- Women diagnosed as having PCOS before pregnancy should be screened for gestational diabetes in early pregnancy
      • Refer to specialized obstetric diabetic service if abnormalities detected (evidence level IIb[B])
    • Guidelines (RCOG, May 2003)
      • 3-Measurement of fasting cholesterol, lipids and triglycerides should be offered to patients with PCOS, since early detection of abnormal levels might encourage improvement in diet and exercise (Evidence level III[C])
      • 4- Olig- and amenorrhoeic women with PCOS may develop endometrial hyperplasia and later carcinoma. It is good practice to recommend treatment with progestogens to induce withdrawal bleed at least every 3-4 months (Evidence level IIa[B])
    • Guidelines (RCOG, May 2003)
      • 5- Evidence has accumulated demonstrating safety and efficacy of insulin-sensitizing agents in the management of short-term complications of PCOS, particularly anovulation. Long-term use of these agents for avoidance of metabolic complications of PCOS cannot as yet be recommended (Evidence level IV[B])
      • 6- No clear consensus regarding regular screening of women with PCOS for later development of diabetes and dyslipidemia
      • Obese women with strong family history of cardiac disease or diabetes should be assessed regularly in a general practice or hospital outpatient setting. Local protocols should be developed and adapted (Evidence level IV[C])
    • Guidelines (RCOG, May 2003)
      • Young women diagnosed with PCOS should be informed of the possible long-term risks to health that are associated with their condition. They should be advised regarding weight and exercise (Evidence level III[C])
    • Thank you