Polycystic Ovarian Disease

Polycystic Ovarian Syndrome
Heval Mohamed Kelli MS-3
October 27, 2010
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
Core Features
Area 1 represents subjects fulfilling the 1990 NIH criteria for PCOS.
Areas 2 and 3 added by the 2003 Rotterdam criteria
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%
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
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 ?
High LH—Increased ovarian theca cells-Increase the production of androgens
(testosterone, androstenedione)–
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
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
Signs and symptoms
Menstrual abnormality- Amenorrhea or Oligomenorrhea
Hirsutism- Depend on ethnic groups
Male pattern alopecia
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
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
Thyroid dysfunction
Complication & Risk
Risk of endometrial cancer
Insulin resistance & DM-II
Metabolic syndrome: ↑TG, WC, BP, fasting
glucose & ↓HDL
Obesity related disorders: Sleep apnea
Mood disorders & Depression
Pregnancy complications
Gestational diabetes
Large birth weight
Miscarriage - 45 to 50% risk
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
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.
Diagnosis & Work up-2
Serum hCG- r/o pregnancy
Documentation of unexplained Hyperandrogenemia
• 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.
Diagnosis & Work up-3
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
• 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
Diagnosis & Work up-4
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
Diagnosis & Work up-5
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
Diagnosis & Work up-6
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
ID of endometerial changes.
Diagnosis & Work up-6
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)
Reproductive desire (contraception,
desired fertility, etc.)
Clinical need (hirsutism, dysfunctional
bleeding, etc.)
• PCOS is a chronic condition. No cure.
• Management-alleviating the signs and
symptoms to reduce morbidity.
Desire Fertility
Weight loss & Exercise- alone (even as little as 5% to 7%)
may restore ovulation in up to 80% of overweight or obese
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
No Desire for Fertility
Androgen receptor blockers (spironolactone, cyproterone, flutamide)
5-alpha-reductase inhibitors (finasteride)
Mechanical or local hair removal (depilation and epilation)
VANIQA (Topical eflornithine cream)
Topical antibiotics (erythromycin and clindamycin),
Oral antibiotics (doxycycline, minocycline & erythromycin)
Weight loss & Exercise
Ovarian Diathermy (Drilling)
-Laser fiber or electrosurgical
needle punctures the ovary 4 to
10 times.
-Up to 80 percent of patients will
-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
Ovarian Diathermy (Drilling)
• Weight loss and Metformin may prevent
diabetes and atherosclerosis.
• Lifestyle modification-physical activity
and healthy diet
• Family history-Screening at younger age
• Patients should be evaluated every 3
months for treatment response and
development of any adverse effects.
Once stable, monitoring is every 6
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
Everyone For Everything