© Copyright Annals of Internal Medicine, 2011 Ann Int Med. 154 (3): ITC2-1. Terms of Use The In the Clinic ® slide sets are owned and copyrighted by.

© Copyright Annals of Internal Medicine, 2011Ann Int Med. 154 (3): ITC2-1.

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© Copyright Annals of Internal Medicine, 2011Ann Int Med. 154 (3): ITC2-1.

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© Copyright Annals of Internal Medicine, 2011Ann Int Med. 154 (3): ITC2-1.

in the clinic

The Polycystic Ovary Syndrome

© Copyright Annals of Internal Medicine, 2011Ann 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, 2011Ann 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, 2011Ann 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

*European Society for Human Reproduction and Embryology and American Society for Reproductive Medicine

NOTE: Polycystic ovaries alone ≠ PCOS

Most obese women w/oligomenorrhea have PCOS

© Copyright Annals of Internal Medicine, 2011Ann 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, 2011Ann 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, 2011Ann 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, 2011Ann 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, 2011Ann Int Med. 154 (3): ITC2-1.

What other diagnosis should clinicians consider? Late-onset congenital adrenal hyperplasia

Androgen-producing neoplasms

Cushing syndrome

Hyperprolactinemia

Pregnancy

HypothyroidismAlternate 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, 2011Ann Int Med. 154 (3): ITC2-1.

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

CLINICAL BOTTOM LINE: Diagnosis...

© Copyright Annals of Internal Medicine, 2011Ann 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, 2011Ann 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, 2011Ann 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, 2011Ann 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, 2011Ann 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, 2011Ann Int Med. 154 (3): ITC2-1.

Cyclic progestin

Oral contraceptives with combo estrogen + progestin

Insulin-sensitizing drugs

Weight loss

What interventions minimize the risks of prolonged amenorrhea?

© Copyright Annals of Internal Medicine, 2011Ann 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, 2011Ann 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, 2011Ann 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, 2011Ann Int Med. 154 (3): ITC2-1.

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

CLINICAL BOTTOM LINE: Treatment...