• IN THE NAME OF GOD

• Elham Faghihimani• endocrinologist

Diagnosis and Treatment of Polycystic Ovary

Syndrome: An Endocrine Society Clinical Practice

Guideline

J Clin Endocrin Metab. October 22, 2013

Diagnosis of PCOS

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

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

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).

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

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

diagnosis

• history

• Physical examination

• Laberatory tests

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])

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.

• 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

Depending on presentation

• Hypothalamic amenorrhea• Primary ovarian failure• Androgen secreting tumor• Cushing syndrom• acromegaly

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)

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)

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)

• 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

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

Ferriman-gallwey score

Laboratory Tests for the Differential Diagnosis of Androgen Excess

• Initial Testing • Total testosterone

• Prolactin

• Thyroid-stimulating hormone

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.

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)

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

• 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

• 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

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

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

• 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

• 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

• THANK YOU FOR YOUR ATTENTION