1. IN THE NAME OF GOD Elham Faghihimani endocrinologist

2. Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline J Clin Endocrin Metab. October 22, 2013

3. Diagnosis of PCOS two of the three following criteria are met: androgen excess, ovulatory dysfunction, or polycystic ovaries (PCO)

4. Androgen status Clinical hyperandrogenism may include hirsutism (defined as excessive terminal hair that appears in a male pattern), acne, or androgenic alopecia. Biochemical hyperandrogenism refers to an elevated serum androgen level

5. Menstrual history Anovulation may manifest as frequent bleeding at intervals 21 d or infrequent bleeding at intervals 35 d. bleeding may be anovulatory despite falling at a normal interval (25–35 d).

6. Ovarian appearance The PCO morphology has been defined by the presence of 12 or more follicles 2–9 mm in diameter and/or an increased ovarian volume 10 mL (without a cyst or dominant follicle) in either ovary

7. CASES 25yrs, female, irregular mense, hirsutism and normal US of ovaries. 19yrs, female, amenorrhea for2yrs and polycystic ovaries on US 40yrs, female, infertile, irregular mense, acne and hirsutim, large ovaries

8. diagnosis history Physical examination Laberatory tests

9. Disorders that mimic the clinical features of PCOS are excluded. thyroid disease, hyperprolactinemia, and nonclassic congenital adrenal hyperplasia (primarily 21-hydroxylase deficiency by serum 17-hydroxyprogesterone [17-OHP])

10. CAH Screening may first be carried out by obtaining an 8:00 a.m. serum level of 17-hydroxyprogesterone in an anovulatory patient on any day A level of less than 2 ng/mL effectively rules out this diagnosis The diagnosis of nonclassic adrenal hyperplasia can be made if the basal 17-hydroxyprogesterone level is higher than 8 ng/mL. No further testing is required in these cases.

11. Values between 2 and 8 ng/Ml an ACTH stimulation test should be used to distinguish nonclassic adrenal hyperplasia from PCOS. A rise of the 17(OH)P Level to at least 10 ng/mL 60 minutes after intravenous injection of ACTH has been considered diagnostic of nonclassic adrenal hyperplasia

12. Depending on presentation Hypothalamic amenorrhea Primary ovarian failure Androgen secreting tumor Cushing syndrom acromegaly

13. MORBIDITY Infertility Pregnancy complications Endometrial cancer Obesity Nonalcoholic fatty liver disease (NAFLD) obstructive sleep apnea (OSA) Depression Type 2 diabetes mellitus OGTT( every 3-5 years )

14. Cardiovascular risk We recommend that adolescents and women with PCOS be screened for the following cardiovascular disease risk factors family history of early cardiovascular disease, cigarette smoking, IGT/T2DM, hypertension, dyslipidemia, OSA, and obesity (especially increased abdominal adiposity)

15. Treatment Hormonal contraceptives lifestyle therapy Metformin ( women who have T2DM or IGT who fail lifestyle modification, For women with menstrual irregularity who cannot take or do not tolerate HCs, we suggest metformin as second-line therapy)

16. Insulin resistance is associated with abnormal responses of the ovarian follicle to FSH, which lead to anovulation and androgen secretion. This results in noncyclic formation of estrogen from androgens in peripheral tissues. Estradiol together with elevated androgen and insulin levels gives rise to abnormal gonadotropin secretion. This creates an anovulatory state favoring continuous formation of LH, steroid precursors, androgen, and estrogen

17. Hirsutism Hirsutism is defined as the presence of terminal (coarse) hair in locations at which hair is not commonly found in women virilization is a more severe form of androgen excess and implies significantly higher rates of testosterone production. Its manifestations include temporal balding, deepening of voice, decreased breast size, increased muscle mass, loss of female body contours, and clitoral enlargement

18. Ferriman-gallwey score

19. Laboratory Tests for the Differential Diagnosis of Androgen Excess Initial Testing Total testosterone Prolactin Thyroid-stimulating hormone

20. Laboratory TESTS A testosterone value of three times the upper- normal range (or >2 ng/mL) suggests a neoplasm, particularly if the clinical history supports this diagnosis. Lower serum testosterone levels occasionally may be associated with virilizing ovarian tumors Transvaginal ultrasonography is the most sensitive method for the detection of an ovarian tumor. If DHEAS levels exceed 8 µg/mL, adrenal imaging by computed tomography (CT) or MRI should be ordered.

21. Further Testing Based on Clinical presentation 17-Hydroxyprogesterone (8:00 a.m.) 17(OH)P 60 min after intravenous ACTH Cortisol (8:00 a.m.) after 1 mg dexamethasone at midnight DHEAS, Testosterone Imaging of ovaries (transvaginal ultrasonography) Imaging of adrenals (abdominal ultrasonography, CT, MRI)

22. TREATMENT Oral Contraceptives Oral contraceptives reduce circulating testosterone and androgen precursors by suppression of LH and stimulation of SHBG levels, thereby reducing hirsutism in hyperandrogenic patients

23. Spironolactone an aldosterone antagonist structurally related to progestins. inhibiting steroidogenesis and acting as an androgen antagonist, AND a significant effect in inhibiting 5α-reductase activity Dose: 50 to 400 mg daily Not recommended in pregnancy

24. Cyproterone Acetate acts as an antiandrogen by competing with DHT and testosterone for binding to the androgen receptor daily in doses of 50 to 100 mg on days 5 through 15 of the treatment cycle ethinyl estradiol is added, it is usually administered in 50-µg doses on days 5 through 26

25. Finasteride inhibits 5α-reductase activity Dose: 5 mg/day Not recommended in pregnancy

26. Metformin and Thiazolidinediones metformin (1500 to 2700 mg/day) for 6 months significantly reduces hirsutism 30 mg/day of pioglitazone studies suggested that insulin-sensitizing agents may be used in the treatment of hirsutism, especially for women who do not wish to use other oral agents. A moderate diet and exercise program should be recommended

27. Most patients with PCOS and idiopathic hirsutism respond to this strategy within 1 year. Patients should be encouraged to continue treatment for at least 2 years

28. 25yrs, female, irregular mense, hirsutism and normal US of ovaries. 19yrs, female, amenorrhea for2yrs and polycystic ovaries on US 40yrs, female, infertile, irregular mense, acne and hirsutim, large ovaries

29. THANK YOU FOR YOUR ATTENTION