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Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome. Heval Mohamed Kelli MS-3 October 27, 2010. http://www.morethancardio.com/pcos-awareness/. Definition. ACOG and NIH: hyperandrogenic chronic anovulation state excluding other causes. Anovulation + Hyperandrogenism & Exclusion of other disorders (NIH)

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Polycystic Ovarian Syndrome

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  1. Polycystic Ovarian Syndrome Heval Mohamed Kelli MS-3 October 27, 2010 http://www.morethancardio.com/pcos-awareness/

  2. Definition ACOG and NIH: hyperandrogenic chronic anovulation state excluding other causes. Anovulation + Hyperandrogenism & Exclusion of other disorders (NIH) Polycystic ovaries by US-nonspecific (Rotterdam 2 of 3) Originally called Stein-Leventhal Syndrome

  3. Core Features Area 1 represents subjects fulfilling the 1990 NIH criteria for PCOS. Areas 2 and 3 added by the 2003 Rotterdam criteria

  4. Incidence PCOS is one of the most common endocrine disorders of women in the reproductive age group, with a incidence of US 4-12% (NIH criteria) World wide 6.5-8% (NIH criteria) Prevalance-PCOS with Normogonadotrophic anovulation Rotterdam- 91% NIH-55% Higher in Mexican-American than White or African-American women. (No difference b/w AA & CAU women) Higher in those with gestational diabetes Those with first-degree relatives with PCOS

  5. Etiology Unknown exact cause? • A genetic disorder with an autosomal dominant mode of inheritance? • A multifactorial genetic disorder? • Hypersecretion of adrenal androgens? • Hypersecretion of ovarian androgens? • Insulin resistance-Decreased SHBG ?

  6. Pathophysiology High LH—Increased ovarian theca cells--Increase the production of androgens (testosterone, androstenedione)–Hyperandrogenism-Hirsutism/Acne.. Androstenedione aromatize to estrone within adipocytes- +feedback on Pit to secrete LH. Estrone= weak estrogen- Increased Hyperinsulinemia/Insulin resistance- pulse Increase GnRH pulse frequency, decreased SHBG--Hyperandrogenism Obesity (50% to 65% PCOS pts), may increase the insulin resistance and hyperinsulinemia

  7. Pathophysiology

  8. Pathophysiology • Hormonal Studies in Women with PCOS show: • Increased LH: FSH • Estrone greater than estradiol • Androstenedione (Dehydroepiandrosterone-sulfate (DHEA-S)) at the upper limit of normal or increased • Testosterone at the upper limit of normal or slightly increased

  9. Signs and symptoms Menstrual abnormality-Amenorrhea or Oligomenorrhea Hirsutism- Depend on ethnic groups Male pattern alopecia Acne Infertility Weight gain and obesity (50%) Insulin abnormalities-38 % IGT, 7.5% DM-II Acanthosis Nigricans- HAIR-AN syndrome (Hyperandrogenism, insulin resistance, AN) Ovarian Cysts Mood Swings, depression Sleep Apnea Absence of breast development

  10. Differential Diagnosis Androgen-excess disorders Late onset non-classic 21 hydroxylase deficiency Idiopathic hirsutism Syndromes of severe insulin resistance e.g. HAIR-AN syndrome Ovarian androgen-secreting tumours Use of anabolic or androgenic drugs Cushing’s syndrome Ovulatory disorders Hypothalamic and pituitary disorders causing amenorrhoea Premature ovarian failure Others Thyroid dysfunction Hyperprolactinaemia

  11. Complication & Risk Infertility Risk of endometrial cancer Insulin resistance & DM-II CVD Metabolic syndrome: ↑TG, WC, BP, fasting glucose & ↓HDL Obesity related disorders: Sleep apnea Mood disorders & Depression Pregnancy complications

  12. Pregnancy Gestational diabetes Large birth weight Miscarriage - 45 to 50% risk Preeclampsia Pregnancy-induced hypertension Premature birth Prenatal care Wt loss improved pregnancy rate Carefully monitoring the pregnancy and routine prenatal care. Maintaining a healthy PCOS pregnancy diet: fruits, vegetable and grains. Getting prompt intervention if complications occur

  13. Diagnosis & Work up-1 History-menstrual pattern, duration of androgen excess, hirsutism, medications, FH(DM & CVD), life styles (Tob/Etoh, exercise). Physical exam- body hair distribution, acne, temporal balding, acanthosis, pelvic exam to assess ovarian size.

  14. Diagnosis & Work up-2 Laboratory: Serum hCG- r/o pregnancy Documentation of unexplained Hyperandrogenemia Testosterone • A total testosterone more reliable than a free testosterone • AES recommends Free Test-sensitive indicator- Directly or FAI calculated based on total test & SHBG(supranormal level in 60% of PCOS pts) • Testosterone values may be normal in PCOS. • Oral contraceptives will lower total testosterone (3 months off oral contraceptives is best to get a “true” testosterone value). • Most testosterone values in PCOS will be ≤150 ng/dL (≤5.2 nmol/L). • Testosterone values of ≥200 ng/dL (≥6.9 nmol/L) warrant consideration of an ovarian or adrenal tumor.

  15. Diagnosis & Work up-3 Laboratory: Dehydroepiandrosterone-sulfate (DHEA-S)- Poor sp/sn • DHEA-S values may be normal or slightly elevated in PCOS. • DHEA-S values ≥800 µg/dL (21.7 µmol/L) warrant consideration of an adrenal tumor. • Maybe useful in cases of rapid virilization (LH/FSH) ratio-Poor sp/sn • A ratio ≥2.0 is suggestive of PCOS- poor sp/sn • Gonadotropin levels are affected by oral contraceptives FSH level- r/o primary ovarian failure

  16. Diagnosis & Work up-4 Laboratory: Evaluation of Metabolic abnormalities 75-g oral glucose-tolerance test (OGTT) -31% of PCOS pt report IGT Fasting lipid profile- often abnormal: ↓HDL, ↑LDL, ↑ TG

  17. Diagnosis & Work up-5 Laboratory: Exclusion of disorders with similar symptoms: Prolactin r/o hyperprolactinemia. Mild elevation in PCOS (5-30%pts) TSH r/o hypothyroidism 17-hydroxyprogesteron r/o Late-onset CAH -morning, fasting, unstimulated level of <200 ng/dL (<6 nmol/L) is normal. 24-hour urine free cortisolr/o Cushing syndrome. Mild elevation in PCOS

  18. Diagnosis & Work up-6 Ultrasound Polycystic ovaries are defined as 12 or more follicles in at least 1 ovary measuring 2-9 mm in diameter or a total ovarian volume of >10 cm3 The presence of one polycystic ovary is sufficient for diagnosis ID of endometerial changes. http://www.infertility.net.au/causeOvulation.htm

  19. Diagnosis & Work up-6 Ultrasound http://www.ivf-infertility.com/infertility/pcos.php

  20. Treatment Goals • Interrupt the disorder’s positive cycle. • Reduce circulating androgen levels • Protect the endometrium from unopposed estrogen (reduce risk of endometrial cancer) • Encourage weight loss and healthy lifestyle changes • Induce ovulation when pregnancy is desired • Monitor for the development of DM and CVD and Lower risk factors (smoking cessation, lipid-lowering agents, etc)

  21. Treatments Reproductive desire (contraception, desired fertility, etc.) Clinical need (hirsutism, dysfunctional bleeding, etc.) Prognosis • PCOS is a chronic condition. No cure. • Management-alleviating the signs and symptoms to reduce morbidity.

  22. Treatments Desire Fertility Weight loss & Exercise- alone (even as little as 5% to 7%) may restore ovulation in up to 80% of overweight or obese patients Metformin- Restore ovulation/menses. 40% ovulate on Metformin 6 to 9 months needed for the full effect. ↑SHBG, ↓glucose production & ↑insulin sensitivity Clomiphene-induce ovulation. +Metformin or + Dexamethasone for adrenal androgen excess

  23. Treatments No Desire for Fertility OCP Antiandrogen Androgen receptor blockers (spironolactone, cyproterone, flutamide) 5-alpha-reductase inhibitors (finasteride) Hirsutism Mechanical or local hair removal (depilation and epilation) VANIQA (Topical eflornithine cream) Acne Topical antibiotics (erythromycin and clindamycin), Oral antibiotics (doxycycline, minocycline & erythromycin) Topical BENZOYL PEROXIDE Topical RETINOIDS Weight loss & Exercise Metformin

  24. Treatments Ovarian Diathermy (Drilling) -Laser fiber or electrosurgical needle punctures the ovary 4 to 10 times. -Up to 80 percent of patients will benefit -Anovulatory women may ovulate with clomiphene or Metformin therapy after ovarian drilling. Rarely, oophorectomy is a viable option for women not seeking fertility who exhibit signs and symptoms of ovarian hyperthecosis and accompanying severe hyperandrogenism

  25. Treatments Ovarian Diathermy (Drilling)

  26. Prevention • Weight loss and Metformin may prevent diabetes and atherosclerosis. • Lifestyle modification-physical activity and healthy diet • Family history-Screening at younger age Monitoring • Patients should be evaluated every 3 months for treatment response and development of any adverse effects. Once stable, monitoring is every 6 months.

  27. References Banaszewska B, Duleba A, Spaczynski R: Lipids in polycystic ovary syndrome: Role of hyperinsulinemia and effects of metformin. Am J Obstet Gynecol 194:1266, 2006 Azziz R, Woods KS, Reyna R, et al. The prevalence and features of the polycystic ovary syndrome in an unselectedpopulation. J Clin Endocrinol Metab. Jun 2004;89(6):2745-9 Boomsma CM, Eijkemans MJC, Hughes EG: A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 12:673, 2006 Dokras A, Bochner M, Hollinrake E: Screening women with polycystic ovary syndrome for metabolic syndrome. Obstet Gynecol 106:131, 2005 Goldenberg N, Glueck C (2008). "Medical therapy in women with polycystic ovarian syndrome before and during pregnancy and lactation". Minerva Ginecol60 (1): 63–75

  28. Everyone For Everything

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