1. Polycystic Ovarian Syndrome
Heval Mohamed Kelli MS-3
October 27, 2010

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
And or PO by US ( nonspecific)
Rotterdam require US

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
And or PO by US ( nonspecific)

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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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.

15. 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.
The approach to laboratory and ultrasound evaluations in the diagnosis of PCOS varies widely without any consensus even among experts in the field. Indeed, the diagnosis of PCOS in Europe does not require any hormonal testing, with great importance placed on the finding of polycystic ovaries on ultrasound.

16. 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

17. 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
fasting glucose level between 100 mg/dL and 125 mg/dL is abnormal; abnormal glucose tolerance is 2-hour glucose of mg/dL

18. 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 cortisol r/o Cushing syndrome. Mild elevation in PCOS

19. 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.

20. Diagnosis & Work up-6 Ultrasound

21. 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)

22. 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.

23. 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
The first-line and safest measure to restore ovulation is weight loss (in overweight or obese patients). Weight loss alone (even as little as 5% to 7%) may restore ovulation in up to 80% of overweight or obese patients (possibly by reducing hyperinsulinemia and thus hyperandrogenism).

24. No Desire for Fertility
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
first-line treatment for menstrual irregularities is combination oral contraceptive pills (COCs), which will induce regular menstrual cycles. In addition, COCs reduce androgen levels. Specifically, COCs suppress gonadotropin release, which results in decreased ovarian androgen production. Moreover, the estrogen component increases SHBG levels. The progestin component antagonizes the endometrial proliferative effect of estrogen, thus reducing risks of endometrial hyperplasia due to unopposed estrogen.
Theoretically, progestin-containing pills that contain norethindrone; a third-generation progestin, such as norgestimate or desogestrel; or the newer progestin, drospirenone, are preferred to COCs containing progestins with more androgenic properties. However, no pill has shown superiority compared with another in reducing hirsutism (Sobbrio, 1990).
mechanical or local hair removal
topical eflornithine cream ameliorates hirsutism in many patients (inhibits ornithine decarboxylase, an enzyme in the dermal papilla essential for hair growth inhibits ornithine decarboxylase, an enzyme in the dermal papilla essential for hair growth)
Topical antibiotics typically include erythromycin and clindamycin, whereas oral antibiotics most often used for acne include doxycycline, minocycline, and erythromycin.
TOPICAL BENZOYL PEROXIDE
TOPICAL RETINOIDS

25. Ovarian Diathermy (Drilling)
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.
Studies have shown that up to 80 percent of patients will benefit from such treatment. Many women who fail to ovulate with clomiphene or Metformin therapy will respond when these medications are reintroduced to the system 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

26. Ovarian Diathermy (Drilling)
Treatments
Ovarian Diathermy (Drilling)
Studies have shown that up to 80 percent of patients will benefit from such treatment. Many women who fail to ovulate with clomiphene or Metformin therapy will respond when these medications are reintroduced to the system after ovarian drilling.

27. Prevention Monitoring
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.
Secondary Prevention
Weight loss and metformin may prevent diabetes and atherosclerosis. This is based on extrapolation from clinical trials in non-PCOS populations (prediabetic and diabetic). [90] [91]
Lifestyle modification, including increased physical activity and healthy diet resulting in weight loss, is also likely to prevent diabetes in PCOS, although this has been not been studied as a long-term preventive measure in PCOS. [90]
Patients with PCOS should discuss with their mother and sisters that they have increased risk of PCOS compared with the general population. Screening of younger sisters may lead to early identification of PCOS.
Patient Instructions
Increased physical activity and a healthy diet are indicated in almost all patients with PCOS.
Consultation with a nutritionist is often useful in assisting the patient in healthy food choices.
Caloric restriction is the most important dietary factor in weight loss. The macronutrient composition of the diet has not been shown to make a difference as long as calories are restricted.
Patients should be advised on the chronic nature of PCOS and that symptoms often recur if therapy is prematurely discontinued

28. 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 Ginecol 60 (1): 63–75

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