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  1. 1. PCOS Dr. Mridula A Benjamin Dept of Obs and Gyn RIPAS Hospital, Brunei
  2. 2. Introduction <ul><li>Heterogenous problem </li></ul><ul><li>Commonest hormonal disturbance </li></ul><ul><li>Ovarian expression of metabolic syndrome </li></ul><ul><li>Long term consequences - strategies to screen </li></ul><ul><li>Stein Leventhal syndrome </li></ul>
  3. 3. ASRM/ ESHRE <ul><li>Rotterdam: May 2003 </li></ul><ul><li>Two of three: Oligomenorrhoea & or anovulation </li></ul><ul><li>Hyperandrogenism; Clinical/biochemical </li></ul><ul><li>PCO on USG; 12 or more, 2-9mm,10cm 3 </li></ul><ul><li>Single PCO </li></ul><ul><li>The follicle distribution & increase in stromal echogenecity & volume should be omitted </li></ul><ul><li>Chronic anovulation & hyperandrogenism in absence of other endocrine disorders </li></ul><ul><li>January issue of Fertility & Sterility J, 2004 </li></ul>
  4. 4. Ultrasound <ul><li>Polycystic ovaries </li></ul><ul><ul><li>Bilateral </li></ul></ul><ul><ul><li>Multiple cysts </li></ul></ul><ul><ul><li>Cyst diam <2-9mm </li></ul></ul><ul><ul><li>Stroma increased </li></ul></ul><ul><li>Multicystic ovaries </li></ul><ul><ul><li>Bilateral </li></ul></ul><ul><ul><li>Multiple cysts </li></ul></ul><ul><ul><li>Cyst diam > 6-10 mm </li></ul></ul><ul><ul><li>Stroma not increased </li></ul></ul>
  5. 8. Gross appearance of ovaries <ul><li>Enlarged bilaterally and have a smooth thickened avascular capsule </li></ul><ul><li>On cut section, subcapsular follicles in various stages of atresia are seen </li></ul><ul><li>Microscopically luteinizing theca cells are seen </li></ul>
  6. 11. <ul><li>The best biochemical markers of hyperandrogenism are </li></ul><ul><li>free testosterone levels or free androgen index </li></ul><ul><li>Not all patients with PCOS have elevated circulating androgen levels </li></ul><ul><li>Routine measurement of androstenedione cannot be recommended </li></ul><ul><li>DHEAS is raised in small fraction of patient with PCOS levels </li></ul>
  7. 12. <ul><li>LH levels are elevated in 60% women with PCOS </li></ul><ul><li>LH/FSH ratios can be elevated in up to 95% of women with PCOS if women with recent ovulation are excluded </li></ul><ul><li>LH levels are not necessary for clinical diagnosis of PCOS </li></ul><ul><li>Implications?? High miscarriage / low fertility </li></ul><ul><li>The chances of ovulation or pregnancy rates using CC or HMG are unaffected </li></ul>
  8. 13. <ul><li>PCOS should be excluded from other disorders in which hirsutism and menstrual irregularities are prominent </li></ul><ul><li>Congenital adrenal hyperplasia </li></ul><ul><li>Cushing's syndrome </li></ul><ul><li>Androgen-secreting tumors </li></ul><ul><li>In oligo/anovulation: </li></ul><ul><li>E2 & FSH to exclude hypogonadotrophic hypogonadism (central origin of ovarian dysfunction) </li></ul>
  9. 14. <ul><li>Thyroid disorders in PCOS patients are not more common than in other young women, and TSH is unnecessary </li></ul><ul><li>In hyperandrogenic females: Prolactin </li></ul>
  10. 15. 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
  11. 16. Prevalence <ul><li>PCO on ultrasound - 20%-33% </li></ul><ul><li>Oligomenorrhea - 4 – 21 % </li></ul><ul><li>Oligomenorrhea + hyperandrogenism - 3.5 – 9 % </li></ul>
  12. 17. Pathogenesis (etiology?) <ul><li>Hypersecretion of adrenal androgens? </li></ul><ul><li>Hypersecretion of ovarian androgens? </li></ul><ul><li>A genetic disorder with an autosomal dominant mode of inheritance? </li></ul><ul><li>A multifactorial genetic disorder? </li></ul>
  13. 18. 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
  14. 19. Obesity Insulin Free testosterone SHBG IGF-1 5-alfa reductase activity is stimulated IGF*** insulin like growth factor
  15. 20. Obesity and insulin resistance <ul><li>Diminished biological response to insulin </li></ul><ul><li>In both obese and non obese </li></ul><ul><li>In 40% </li></ul><ul><li>More in obese and oligomenorrhoeic </li></ul><ul><li>Euglycaemia at expense of hyperinsulinaemia </li></ul><ul><li>Obesity more of central -35-60% </li></ul>
  16. 21. 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
  17. 22. Presentation <ul><li>Amenorrhea- </li></ul><ul><li>Oligomenorrhea </li></ul><ul><li>Infertility </li></ul><ul><li>Hirsutism </li></ul><ul><li>Obesity </li></ul><ul><li>Acne Vulgaris </li></ul><ul><li>Asymptomatic </li></ul>
  18. 24. Laboratory studies <ul><li>Increased androgen levels in blood (testosterone and androstendione) </li></ul><ul><li>Increased LH, exaggerated surge </li></ul><ul><li>Increased fasting insulin </li></ul><ul><li>Increased prolactin </li></ul><ul><li>Increased estradiol and estrone levels </li></ul><ul><li>Decreased SHBG levels </li></ul>
  19. 25. Long term risks in PCOS <ul><li>Definite </li></ul><ul><li>Type 2 diabetes(15%), IGT( 18-20%) </li></ul><ul><li>Dyslipidemia (Hypercholesterolemia with diminished HDL2 and increased LDL) </li></ul><ul><li>Endometrial cancer (OR 3.1 95% CI 1.1 -7.3) </li></ul>
  20. 26. <ul><li>Possible </li></ul><ul><li>Hypertension </li></ul><ul><li>Cardiovascular disease </li></ul><ul><li>Gestational diabetes mellitus </li></ul><ul><li>Pregnancy-induced hypertension </li></ul><ul><li>Ovarian cancer </li></ul><ul><li>Unlikely </li></ul><ul><li>Breast cancer </li></ul>Long term consequences
  21. 27. Management <ul><li>Symptom oriented </li></ul><ul><li>Diet & exercise </li></ul><ul><li>Wt. loss </li></ul><ul><li>Improves both symptoms & endocrine profile </li></ul><ul><li>BMI >30kg/ m 2 </li></ul><ul><li>Keep CHO content down, avoid fatty food </li></ul><ul><li>Obesity clinics </li></ul>
  22. 28. Contd <ul><li>Menstrual irregularities </li></ul><ul><li>OCP- Yasmin, Dianette </li></ul><ul><li>ET >10mm(oligo), >15mm(amen)-Withdrawal bleed </li></ul><ul><li>Fails - Endometrial sampling </li></ul>
  23. 29. 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
  24. 31. Mx of Hirsutism <ul><li>Cosmetic </li></ul><ul><li>Medical- 6-7 months </li></ul><ul><li>Cyproterone acetate+ EE, Spironolactone </li></ul><ul><li>Reliable contraception </li></ul><ul><li>Flutamide & Finasteride - Rare </li></ul>
  25. 32. Reproductive Endocrinologist <ul><li>S.testosterone > 5nmol/L </li></ul><ul><li>Rapid onset hirsutism </li></ul><ul><li>IGT/ Type2 DM </li></ul><ul><li>Refractory symptoms </li></ul><ul><li>Amen. > 6 months </li></ul><ul><li>Subfertility </li></ul>
  26. 33. Guidelines (RCOG, May 2003) <ul><li>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 </li></ul><ul><li>Such patients are at increased risk of developing type II diabetes (Evidence level IIb[C]) </li></ul><ul><li>2- Women diagnosed as having PCOS before pregnancy should be screened for gestational diabetes in early pregnancy </li></ul><ul><li>Refer to specialized obstetric diabetic service if abnormalities detected (evidence level IIb[B]) </li></ul>
  27. 34. Guidelines (RCOG, May 2003) <ul><li>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]) </li></ul><ul><li>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]) </li></ul>
  28. 35. Guidelines (RCOG, May 2003) <ul><li>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]) </li></ul><ul><li>6- No clear consensus regarding regular screening of women with PCOS for later development of diabetes and dyslipidemia </li></ul><ul><li>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]) </li></ul>
  29. 36. Guidelines (RCOG, May 2003) <ul><li>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]) </li></ul>
  30. 37. Thank you