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© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
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© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
in the clinic
The Polycystic
Ovary Syndrome
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
Who is at risk for PCOS?
Factors that seem to increase risk
 Family history
 BMI >30 kg/m2
 >⅓ w/PCOS obese
 ≈⅓ have impaired glucose tolerance
 ≈20% w/ polycystic ovaries asymptomatic
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
What symptoms and signs should
prompt clinicians to consider PCOS?
 Hyperandrogenemia
 Hirsutism, acne, alopecia, acanthosis nigricans
 Menstrual irregularity
 Infertility
 Obesity (particularly abdominal)
 Other signs and symptoms: Hypertension, hyperlipidemia,
CVD; obstructive sleep apnea; depression
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
ESHRE/ASRM* criteria
 First: exclude other medical conditions that cause
irregular menstrual cycles and androgen excess
 Then: confirm ≥2 of following present:
 Oligoovulation or anovulation
 Elevated levels of circulating androgens or clinical
manifestations of androgen excess
 Polycystic ovaries on ultrasonography
 NOTE: Polycystic ovaries alone ≠ PCOS
 Most obese women w/oligomenorrhea have PCOS
*European Society for Human Reproduction and Embryology and American
Society for Reproductive Medicine
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
What is the typical menstruation pattern
in PCOS?
 Oligomenorrhea
 Typically ≥35 days between cycles
 Only 4 to 9 periods/year
 Occasionally, menstruation cycle more normal, but
menses very light
 Some w/PCOS do not menstruate at all
 Consider PCOS: if menstrual irregularity began at
menarche and continued >1 yr
 Consider other diagnoses: if menstrual irregularity
began years after puberty or suddenly worsened
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
How does PCOS affect fertility?
 ≈90% anovulation infertility PCOS-related
 No luteinizing hormone surge, so ovulation doesn’t occur
 Pregnancy can often be achieved
 With lifestyle modifications (weight loss), drug treatments,
or surgical approaches to infertility
 Infertility workup of both partners should precede drug
therapy for infertility
 Refer women w/PCOS and fertility concerns to specialist
PCOS increases risk for pregnancy complications
 Gestational diabetes, pregnancy-induced high BP
and preeclampsia, preterm labor
 Miscarriage (risk unclear)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
Which lab tests are useful in diagnosis?
 Serum testosterone
 Free (bioavail) and total testosterone levels usually increased
 Androstenedione
 May have slightly better sensitivity in US-proven PCOS
 LH, FSH
 High normal LH & normal FSH with ratio >2 consistent with Dx
 Serum prolactin
 May be slightly elevated
 Dehydroepiandrosterone (DHEA)
 Often increased; if markedly so, consider adrenal neoplasia
 Fasting glucose level and glucose tolerance test
 Impaired glucose tolerance in ⅓ with PCOS
 Fasting cholesterol, triglycerides, HDL (for assessment of CV risk)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
Is an imaging study documenting cystic
ovaries necessary for diagnosis?
 Yes, unless diagnosis already clear
 Polycystic ovary morphology on US: 1 of 3 criteria
 Imaging advances allow improved measurement
capabilities and resolution
 Criteria defining polycystic ovaries:
 ≥12 follicles in each ovary (2 to 9 mm diameter)
 Or increased ovarian volume (>10 cm3)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
What other diagnosis should clinicians
consider?
 Late-onset congenital adrenal hyperplasia
 Androgen-producing neoplasms
 Cushing syndrome
 Hyperprolactinemia
 Pregnancy
 Hypothyroidism
Alternate causes of oligo/amenorrhea
Chronic illness, stress, excessive exercise
Eating disorder, poor nutrition, low weight
Thyroid dysfunction, estrogen-secreting &
pituitary tumor, illegal use of anabolic
steroids
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
CLINICAL BOTTOM LINE: Diagnosis...
 Consider PCOS: irregular menstruation, infertility, obesity,
and hyperandrogenemia
 Exclude other conditions causing similar symptoms
 If androgen levels very high: ? adrenal/ovarian neoplasia
 Make diagnosis: if ≥2 of following are present:
 Oligoovulation or anovulation
 Elevated levels of circulating androgens or clinical
manifestations of androgen excess
 Polycystic ovaries on ultrasonography
 Most important part of history: symptom onset
 If symptoms began years after puberty or have suddenly
worsened, other diagnoses more likely
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
What is the role of diet in the
management of patients with PCOS?
 Loss of abdominal fat helps restore ovulation
 Just 2%-5% decrease in total body weight improves
 Menstrual regularity and ovulatory function
 Hirsutism
 Insulin sensitivity
 Response to fertility medication
 Refer patients to dietician for dietary modifications
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
When is drug therapy appropriate, and
what are available options?
 Oral contraceptive
 Regularizes menstruation, reduces hyperandrogenism; improves
body composition and insulin sensitivity
 Spironolactone
 Improves hyperandrogenic manifestations
 Cyproterone acetate
 Potent antiandrogen agent; unavailable in U.S.
 Finasteride
 Potent antiandrogen agent
 Eflornithine
 Slows hair growth everywhere or just on face
 Metformin
 Improves ovulation & glucose tolerance; may reduce testosterone
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
When fertility is the primary concern,
what treatment options are available?
 Lifestyle modifications for weight loss
 Clomiphene citrate
 Estrogen-like hormone increases FSH and LH levels and
improves ovulation chances
 Clomiphene + metformin
 Benefit of adding insulin sensitizer uncertain
 Gonadotropins, if clomiphene-insensitive
 Improves fertility, but often results in follicle overproduction
 Laparoscopic ovarian surgery
 Doesn’t trigger ovarian hyperstimulation
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
What are treatment options for hirsutism?
 Local measures: shaving, waxing, lasers, electrolysis
 Topical eflornithine cream
 Retards hair growth
 Oral contraceptives
 May reduce hirsutism and acne
 Cyproterone (antiandrogen agent) + oral contraceptives
 Effective but reduces libido, causes liver function changes
 Insulin-sensitizing agents
 Not recommended for cosmetic purposes
 Best result: combine systemic + nonsystemic therapies
 Hirsutism slow to respond to therapy (≥6 months)
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
What are the risks for prolonged amenorrhea?
 Elevated estrogen levels cause endometrial proliferation
 Increases risk for endometrial carcinoma
 Disorders with PCOS that  endometrial carcinoma risk:
 Obesity
 Hyperinsulinemia
 Diabetes
 Anovulatory cycles
 High androgen levels
 >3 months amenorrhea: consider progesterone challenge
 ≥1 year amenorrhea In women with PCOS: ultrasound to
measure endometrial thickness and possible biopsy if
endometrium >14 mm
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
What interventions minimize the risks of
prolonged amenorrhea?
 Cyclic progestin
 Oral contraceptives with combo estrogen + progestin
 Insulin-sensitizing drugs
 Weight loss
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
How should clinicians manage follow-up
care for women with PCOS?
 Check menstrual pattern every 3-12 months
 If menses >3 mo apart, initiate Provera challenge and/or
oral contraceptive
 Check hyperandrogenic symptoms every 3-6 months
 Document acne severity and hirsutism, including topical
measures
 Ask about pregnancy plans as clinically appropriate
 Planning needed so patient not on contraindicated drugs in
pregnancy
 Measure weight, waist circumference, and blood
pressure regularly
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
Laboratory tests
 Order fasting glucose or 2-hr glucose tolerance test
annually
 Check fasting total cholesterol, triglyceride, and HDL
cholesterol levels every 1-3 years
 Order Liver function tests only if patient is receiving a
medication known to affect liver function
 Nondrug therapy
 Assess patient readiness to make changes in diet
and/or exercise as clinically appropriate
 Drug therapy
 Check for adverse events as clinically appropriate
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
Does pregnancy in women with PCOS
carry specific risks?
 Increased maternal risk for…
 Gestational diabetes
 Preeclampsia (possibly)
 Hyperstimulation syndrome (if gonadotropins used)
 Increased fetal risk for…
 Preterm birth
 Admission to neonatal ICU
 Reduce risk factors before conception
 Closer follow-up and more fetal monitoring needed
during pregnancy
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.
CLINICAL BOTTOM LINE: Treatment...
 Focus on treating symptoms
 If patient is overweight, encourage weight loss
 If patient is not seeking pregnancy: consider oral
contraceptives, sometimes combined with antiandrogen agent
 If patient is seeking pregnancy: clomiphene commonly used
 Insulin sensitizer (metformin) may also be beneficial
 If patient is pregnant: beware increased complication risk
 Women should report prolonged amenorrhea: so that a
progesterone challenge or endometrial biopsy can be done
© Copyright Annals of Internal Medicine, 2011
Ann Int Med. 154 (3): ITC2-1.