eMedicine Specialties > Obstetrics and Gynecology > Reproductive Endocrinology and Infertility

Polycystic Ovarian Syndrome

Mukhtar I Khan, MD, Assistant Professor of Medicine, Division of Endocrinology, Diabetes & Metabolism, SUNY Upstate Medical University, Syracuse, NY

Updated: Sep 4, 2009

Introduction

Background

Stein and Leventhal were the first to recognize an association between the presence of polycystic ovaries and signs of hirsutism and amenorrhea (eg, oligomenorrhea, obesity).¹ After women diagnosed with Stein-Leventhal syndrome underwent successful wedge resection of the ovaries, their menstrual cycles became regular, and they were able to conceive.² As a consequence, a primary ovarian defect was thought to be the main culprit, and the disorder came to be known as polycystic ovarian disease. Further biochemical, clinical, and endocrinologic studies revealed an array of underlying abnormalities; hence, the condition is now referred to as polycystic ovary syndrome (PCOS), though it may occur in women without ovarian cysts.

Pathophysiology

Women with PCOS have abnormalities in the metabolism of androgens and estrogen and in the control of androgen production. High serum concentrations of androgenic hormones, such as testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEA-S), may be encountered in these patients. However, individual variation is considerable, and a particular patient might have normal androgen levels.

PCOS is also associated with peripheral insulin resistance and hyperinsulinemia, and obesity amplifies the degree of both abnormalities. Insulin resistance in PCOS can be secondary to a postbinding defect in insulin receptor signaling pathways, and elevated insulin levels may have gonadotropin-augmenting effects on ovarian function.

In addition, insulin resistance in PCOS has been associated with adiponectin—a hormone secreted by adipocytes that regulates lipid metabolism and glucose levels; both lean and obese women with PCOS have lower adiponectin levels than women without PCOS.³

A proposed mechanism for anovulation and elevated androgen levels suggests that, under the increased stimulatory effect of luteinizing hormone (LH) secreted by the anterior pituitary, stimulation of the ovarian theca cells is increased. In turn, these cells increase the production of androgens (eg, testosterone, androstenedione). Because of a decreased level of follicle-stimulating hormone (FSH) relative to LH, the ovarian granulosa cells cannot aromatize the androgens to estrogens, which leads to decreased estrogen levels and consequent anovulation. Growth hormone (GH) and insulin-like growth factor–1 (IGF-1) may also augment the effect on ovarian function.⁴

Hyperinsulinemia is also responsible for dyslipidemia and for elevated levels of plasminogen activator inhibitor-1 (PAI-1) in patients with PCOS. Elevated PAI-1 levels are a risk factor for intravascular thrombosis.

Polycystic ovaries are enlarged bilaterally and have a smooth thickened capsule that is avascular. On cut sections, subcapsular follicles in various stages of atresia are seen in the peripheral part of the ovary. The most striking ovarian feature of PCOS is hyperplasia of the theca stromal cells surrounding arrested follicles. On microscopic examination, luteinized theca cells are seen.

Frequency

United States

PCOS is one of the most common endocrine disorders of women in the reproductive age group, with a prevalence of 4-12%.^5,6

International

In various European studies, the prevalence of PCOS was 6.5-8%.^7,8

Age

PCOS affects mostly women of reproductive age.

Clinical

History

Patients with PCOS may present with various clinical features.

• Menstrual abnormalities
  • Patients have abnormal menstruation patterns attributed to chronic anovulation.
  • Some women have oligomenorrhea (ie, menstrual bleeding that occurs at intervals of 35 d to 6 mo, with <9 menstrual periods per y) or secondary amenorrhea (an absence of menstrual for 6 mo). Dysfunctional uterine bleeding and infertility are the other consequences of anovulatory menstrual cycles.
  • The menstrual irregularities in PCOS usually manifest around the time of menarche.
• Hyperandrogenism
  • Hyperandrogenism clinically manifests as excess terminal body hair in a male distribution pattern. Hair is commonly seen on the upper lip, chin, around the nipples, and along the linea alba of the lower abdomen.
  • Some patients have acne and/or male-pattern hair loss (androgenic alopecia).
  • A few patients may also have increased muscle mass, deepening voice, and/or clitoromegaly due to excessive androgens.
• Infertility
  • A subset of women with PCOS are infertile.
  • Most women with PCOS ovulate intermittently. Conception may take longer than in other women, or women with PCOS may have fewer children than they had planned.
• Obesity
  • Obesity is present in nearly half of all women with PCOS.
  • A study comparing the body mass index (BMI) in American and Italian women with PCOS showed that American women had a BMI higher than that of their Italian counterparts.⁹
• Diabetes mellitus: Approximately 10% of women with PCOS have type 2 diabetes mellitus, and 30-40% of women with PCOS have impaired glucose tolerance by the age of 40 years.^10,11
• Sleep apnea: Many women with PCOS have obstructive sleep apnea syndrome. These patients have excessive daytime somnolence and have apnea/hypopnea episodes during sleep.^12,13
• Acanthosis nigricans: Patients with PCOS may have dark, pigmented skin on the nape of their neck, skin folds, knuckles, and/or on elbows.
• Metabolic syndrome
  • In women, metabolic syndrome is characterized by abdominal obesity (waist circumference > 35 in.), dyslipidemia (triglyceride level >150 mg/dL, high-density lipoprotein cholesterol [HDL-C] level < 50 mg/dL), elevated blood pressure, a proinflammatory state characterized by an elevated C-reactive protein level, and a prothrombotic state characterized by elevated PAI-1 and fibrinogen levels.¹⁴
  • Numerous patients with PCOS have characteristics of metabolic syndrome. One study showed a 43% prevalence of metabolic syndrome in women with PCOS.¹⁴
  • Women with PCOS have increased prevalence of coronary artery calcification and a thickened carotid intima media, which may be responsible for subclinical atherosclerosis.

Physical

Physical examination findings are notable for the findings described below.

• Hirsutism: Patients may have excessive body hair in a male distribution pattern and acne. Some patients have virilizing signs, such as male-pattern balding or alopecia, increased muscle mass, deepening voice, or clitoromegaly; these findings should prompt a search for other causes of hyperandrogenism.
• Obesity: Approximately 50% of women with PCOS have abdominal obesity characterized by a waist circumference of greater than 35 in (>88 cm).
• Acanthosis nigricans: This is a diffuse, velvety thickening and hyperpigmentation of the skin. It may be present at the nape of the neck, axillae, area beneath the breasts, intertriginous areas, and exposed areas (eg, elbows, knuckles). In patients with PCOS, acanthosis nigricans is thought to be the result of insulin resistance.
• Blood pressure: Patients with signs and symptoms of metabolic syndrome may have elevated blood pressure with a systolic blood pressure of 130 mm Hg or higher and diastolic blood pressure of 85 mm of Hg or higher.

Differential Diagnoses

Acromegaly
Cushing Syndrome
Hyperprolactinemia
Hypothyroidism

Other Problems to Be Considered

Ovarian hyperthecosis
Congenital adrenal hyperplasia (late-onset)
Androgen-producing tumors of the ovary and adrenals
Drugs (eg, danazol, androgenic progestins)

Workup

Laboratory Studies

• A 1990 expert conference sponsored by National Institute of Child Health and Human Disease (NICHD) of the United States National Institutes of Health (NIH) proposed the following criteria for the diagnosis of PCOS:
  • Oligo-ovulation or anovulation manifested by oligomenorrhea or amenorrhea
  • Hyperandrogenism (clinical evidence of androgen excess) or hyperandrogenemia (biochemical evidence of androgen excess)
  • Exclusion of other disorders that can result in menstrual irregularity and hyperandrogenism
• The European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) recommended that at least 2 of the following 3 features are required for PCOS to be diagnosed¹⁵ :
  • Oligo-ovulation or anovulation manifested as oligomenorrhea or amenorrhea
  • Hyperandrogenism (clinical evidence of androgen excess) or hyperandrogenemia (biochemical evidence of androgen excess)
  • Polycystic ovaries (as defined on ultrasonography)
    • 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 diagnosis of PCOS requires the exclusion of all other disorders that can result in menstrual irregularity and hyperandrogenism. Biochemical and/or imaging studies must be done to rule out these other possible disorders and ascertain the diagnosis.
• Samples for laboratory studies should be drawn early in the morning, with the patient in a fasting state, and, in women with regular menses, between days 5 and 9 of the menstrual cycle.¹⁶
  • Androgen excess can be tested by measuringtotal and free testosterone levels or a free androgen index. An elevated free testosterone level is a sensitive indicator of androgen excess.
  • Other androgens, such as dehydroepiandrosterone-sulfate (DHEA-S), may be normal or slightly above the normal range in patients with PCOS.
  • Levels of sex hormone–binding globulin (SHBG) are usually low in patients with PCOS.
• A serum hCG level should be checked to rule out pregnancy in women with oligomenorrhea or amenorrhea.
• Patients with androgen-secreting ovarian or adrenal tumors can present with hirsutism, amenorrhea, and signs of virilization. However, these tumors are rapidly progressive, and patients have high androgen levels. Their testosterone level may be greater than than 150 ng/dL, and their DHEA-S level may be above 800 mcg/dL.
• Late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency can be ruled out by measuring serum 17-hydroxyprogesterone levels after a cosyntropin stimulation test. A 17-hydroxyprogesterone level of less than 1000 ng/dL, as measured 60 minutes after cosyntropin stimulation, rules out late-onset congenital adrenal hyperplasia.
• Cushing syndrome can be ruled out by checking a 24-hour urine sample for free cortisol and creatinine. levels of urinary free cortisol that are 4-fold the upper limit of normal are diagnostic for Cushing syndrome.¹⁷
• Hyperprolactinemia can be excluded by checking a fasting serum prolactin concentration.
• Because the prevalence of impaired glucose tolerance and type 2 diabetes mellitus is high in women with PCOS, a 75-g oral glucose-tolerance test (OGTT) can be performed. A 2-hour postload glucose value of less than 140 mg/dL indicates normal glucose tolerance, a value of 140-199 mg/dL indicates impaired glucose tolerance, and a value of 200 mg/dL or higher indicates diabetes mellitus.¹⁸
• The fasting lipid profile is often abnormal and shows elevated triglyceride and low-density lipoprotein cholesterol (LDL-C) levels and a decreased HDL-C level.
• The thyroid-stimulating hormone (TSH) should be measured to rule out hypothyroidism, and the FSH level should be checked to rule out primary ovarian failure.
• A serum IGF-1 level should be checked to rule out acromegaly. Serum IGF-1 is a sensitive and specific marker of GH excess. Normal levels rule out GH excess.

Imaging Studies

• Ovarian ultrasonography, preferably accomplished by using a transvaginal approach, can be performed to assess ovarian morphology.
• 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.

Treatment

Medical Care

Medical management is aimed at the treatment of metabolic derangements, anovulation, hirsutism, and menstrual irregularity.

• Metabolic derangements
  • Diet and exercise: In patients with PCOS who are obese, endocrine-metabolic parameters markedly improve after 4-12 weeks of dietary restriction. Their SHBG levels rise and free testosterone levels fall by 2-fold. Serum insulin and IGF-1 levels also decrease. Weight loss in patients with PCOS who are obese is associated with a reduction of hirsutism and a return of ovulatory cycles in 30% of women. A moderate amount of daily exercise increases of levels of IGF-1 binding protein and decreases IGF-1 levels by 20%. Modest weight loss of 2-5% of total body weight can help restore ovulatory menstrual periods in obese patients with PCOS. A daily 500-1000 calorie deficit with 150 minutes of exercise per week can cause ovulation. The Androgen Excess and Polycystic Ovary Syndrome Society recommends lifestyle management as the primary therapy in overweight and obese women with PCOS for the treatment of metabolic complications.¹⁹
  • Metformin: This antidiabetic drug improves insulin resistance and decreases hyperinsulinemia in patients with PCOS.²⁰ Metformin also has a small but beneficial effect on metabolic syndrome.
    • Ascertain that kidney and liver function are normal and that the patient does not have advanced congestive heart failure before starting metformin. The usual starting dose is 500 mg given orally twice a day. Common adverse effects are nausea, vomiting, and diarrhea. Patients who develop these adverse effects can be instructed to decrease the dosage to once a day for a week and then gradually increase the dosage. Also, inform patients that they have a high likelihood of having ovulatory cycles while taking metformin. The US Food and Drug Administration has not approved metformin for this indication; therefore, this use is off label.
• Anovulation
  • Evidence suggests that metformin frequently—but not universally—improves ovulation rates in women with PCOS.²¹ In addition, pretreatment with metformin has been shown to enhance the efficacy of clomiphene for inducing ovulation.²² Whether short-course metformin pretreatment (less than 4 weeks) is as effective as conventional long-course metformin remains uncertain.²³ N-acetylcysteine may also enhance the effect of clomiphene.²⁴
  • Management of infertility: Patients with PCOS who are infertile but desire pregnancy should be referred to a reproductive endocrinologist for further evaluation and management of infertility.
• Hirsutism
  • Hair removal: Short-term nonpharmacologic treatments of hirsutism include shaving and use of chemical depilatories and/or bleaching cream.²⁵ Plucking or waxing unwanted hair can result in folliculitis and ingrown hairs. Long-term measures include techniques such as electrolysis and laser treatment of unwanted hairs.
  • Weight reduction: Weight reduction decreases androgen production in women who are obese; therefore, losing weight can slow hair growth.
  • Oral contraception: Women who do not wish to become pregnant can be effectively treated for hirsutism with oral contraceptives.²⁶ Oral contraceptives slow hair growth in 60-100% of women with hyperandrogenemia. Therapy can be started with a preparation that has a low dose of estrogen and a nonandrogenic progestin. Preparations that have norgestrel and levonorgestrel should be avoided because of their androgenic activity.
  • Spironolactone: Antiandrogens, such as spironolactone, are effective for hirsutism.²⁷ Spironolactone 50-100 mg twice daily is an effective primary therapy for hirsutism. Because of the potential teratogenic effects of spironolactone, patients require an effective form of contraception (eg, an oral contraceptive). Adverse effects of spironolactone include GI discomfort, and irregular menstrual bleeding (which can be managed by adding an oral contraceptive).
  • Eflornithine: Eflornithine (Vaniqa) is a topical cream that can be used to slow hair growth. Eflornithine works by inhibiting ornithine decarboxylase, which is essential for the rapidly dividing cells of hair follicles.
• Menstrual irregularity
  • This is treated with an oral contraceptive, which not only inhibits ovarian androgen production but also increases SHBG production.
  • Pregnancy should be excluded before therapy with oral contraceptives is started.

Surgical Care

Surgical management is aimed mainly at restoring ovulation.

• Ovarian wedge resection: This procedure has fallen out of favor because of postoperative adhesion formation and the introduction of ovulation-inducing medications.
• Laparoscopic surgery: Various laparoscopic methods, including electrocautery, laser drilling, and multiple biopsy, have been used with the goal of creating focal areas of damage in the ovarian cortex and stroma. Potential complications include formation of adhesions (although this is less common than with traditional surgical approaches) and ovarian atrophy. Multiple pregnancy rates are lower with ovarian drilling than with gonadotrophin treatment (1% versus 16%), but there are ongoing concerns about the long-term effects on ovarian function.²⁸

Consultations

• An endocrinologist should be consulted for follow-up evaluations of biochemical and metabolic derangements.
• A reproductive endocrinologist should be consulted if the patient is infertile and desires pregnancy.

Diet

• PCOS patients who have impaired glucose tolerance should start a comprehensive program of diet and exercise to reduce their risk of developing diabetes mellitus.
• Obese women with PCOS can benefit from a low-calorie diet for weight reduction.
• A diet patterned after the type 2 diabetes diet has been recommended for PCOS patients.²⁹ This diet emphasizes increased fiber; decreased refined carbohydrates, trans fats, and saturated fats; and increased omega-3 and omega-9 fatty acids. Omega-3 fatty acid supplementation has been shown to reduce liver fat content and other cardiovascular risk factors in women with PCOS, including those with hepatic steatosis, although these effects have not yet been proven to translate into a reduction in cardiometabolic events.³⁰
• Women with abnormal lipid profile need to be counseled on ways to manage the dyslipidemia. Such ways include eating a diet low in cholesterol and saturated fats and increasing physical activity. Guidelines from the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) (2001) serve as a guide for the treatment of women with PCOS and dyslipidemia.
• Accumulating evidence suggests that vitamin D deficiency may contribute to the development of the metabolic syndrome, and one study found insufficient levels of 25-hydroxyvitamin D (<30 ng/ml) in almost three quarters of PCOS patients, with lower levels in those with the metabolic syndrome than in those without (17.3 versus 25.8 ng/ml, respectively; p<0.05).³¹

Activity

• Encourage moderate physical activity in these patients, provided they have no contraindications to it.

Medication

Drugs used in the treatment of PCOS include metformin (off-label use), spironolactone, eflornithine (topical cream to treat hirsutism), and oral contraceptives. Oral contraceptives containing a combination of estrogen and progestin increase SHBG levels and thereby reduce the free testosterone level. LH and FSH levels are also suppressed. This restores cyclic exposure of the endometrium to estrogen-progestin, with the resumption of menstrual periods and decreased hirsutism. However, the use of oral contraceptives may be associated with an increased risk of thrombosis and metabolic abnormalities.

An oral contraceptive containing ethinyl estradiol and a progestin with minimal androgenic activity, such as norgestimate, norethindrone, or desogestrel, should be selected. Ethinyl estradiol combined with drospirenone (Yasmin) has a progestin that acts as an antiandrogen and thus has added antiandrogenic effects.

Withdrawal bleeding can be induced with medroxyprogesterone (Provera) given for 5-10 days before the start of oral contraceptive therapy.

Hypoglycemic agents

These agents reduce blood glucose levels.

Metformin (Glucophage)

Reduces insulin resistance; insulin sensitizer. Hepatic glucose output decreased. Peripheral insulin-stimulated uptake increased.

Dosing

Adult

500 mg PO bid or 850 mg PO qd; not to exceed 2500 mg/d

Pediatric

Not established

Interactions

Effect decreases with diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, isoniazid, sympathomimetics, and calcium channel blockers; toxicity increases with cationic drugs (eg, amiloride, digoxin); procainamide may interact by competing for common renal tubular transporting systems; cimetidine increases peak plasma and whole-blood concentrations

Contraindications

Documented hypersensitivity; renal impairment with serum creatinine (Cr) >1.4 mg/dL (women) or a Cr clearance (CrCl) of <60 mL/min; any condition resulting in low CrCl, eg, cardiovascular collapse from acute myocardial infarction, septicemia, and metabolic acidosis with or without coma (including diabetic ketoacidosis); temporarily withhold before or during radiologic procedure involving use of IV iodinated contrast material and restart 48 h after procedure and after renal function reevaluated and found normal

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Commonly encountered adverse reactions include anorexia, nausea, vomiting, diarrhea, epigastric fullness, constipation, and heartburn

Antihypertensive agents

Spironolactone has been used to treat hirsutism.

Spironolactone (Aldactone)

Potassium-sparing diuretic that can be used to treat hirsutism.

Dosing

Adult

50-200 mg/d PO qd or divided bid

Pediatric

Not established

Interactions

Toxicity increases with potassium-sparing diuretics, potassium, and indomethacin; angiotensin-converting enzyme (ACE) inhibitors may increase serum-potassium levels; may decrease effect of anticoagulants

Contraindications

Documented hypersensitivity; renal failure; anuria; hyperkalemia; patients receiving other potassium-sparing diuretics or potassium supplements

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Hyperkalemia may occur but generally not encountered in patients with normal renal function; GI discomfort, irregular menstrual bleeding

Topical hair-removal agents

Eflornithine cream can be used to treat androgen excess.

Eflornithine (Vaniqua)

Indicated for reduction of unwanted facial hair in women. Interferes with ornithine decarboxylase in skin hair follicles that is needed for hair growth. Not depilatory but appears to retard hair growth, slowing hair growth and improving appearance where applied. Improvement may be seen as soon as 4-8 wk, though 6 mo may be required. In clinical studies, hair returned to previous condition 8 wk after discontinuation. Studied only on face and adjacent involved areas under chin of individuals with hypertrichosis; therefore, limit use to these areas. Patients likely need other hair-removal methods in conjunction.

Dosing

Adult

Apply thin layer to affected and adjacent involved areas q8h; do not wash treated area for at least 4 h after application

Pediatric

<12 years: Not recommended >12 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

For external use only; transient stinging or burning may occur when applied to abraded or broken skin

Oral contraceptives

These agents reduce the secretion of LH and FSH from the pituitary by decreasing amount of gonadotropin-releasing hormones. All oral contraceptives decrease ovarian androgen production. By inhibiting gonadotropin secretion and, therefore, tertiary follicle development, ovarian secretion of testosterone and androstenedione is decreased. All oral contraceptives increase SHBG and, therefore, reduce free testosterone. Evidence indicates that high doses of contraceptive progestins may inhibit 5-reductase. Oral contraceptives also decrease production of adrenal androgens, particularly DHEA-S.

Different contraceptive preparations have different effects on ovarian androgen production and SHBG. However, they all reduce levels of free testosterone equally (by approximately 50%). Free testosterone levels achieved with oral contraceptive preparations are unrelated to the increased levels of SHBG. Preparations that have high SHBG are associated with high total testosterone levels.

Ethinyl estradiol (Estinyl)

Reduces secretion of LH and FSH from pituitary by decreasing amount of gonadotropin-releasing hormones.
Use ethinyl estradiol 30-35 mg combined with any form of progesterone.
Restoration of regular menstrual cycles prevents endometrial hyperplasia associated with anovulation. Improvements of hyperandrogenic effects are seen in 60-100% of women but usually require a least 6-12 mo of use. Perform pregnancy test before therapy. If the patient has had no menstrual period for 3 mo, induce withdrawal bleeding with medroxyprogesterone acetate (Provera) 5-10 mg/d for 10 d, then begin therapy with oral contraceptives.

Dosing

Adult

1 tab PO qd

Pediatric

Administer as in adults; only after menarche

Interactions

May reduce hypoprothrombinemic effects of anticoagulants; may reduce estrogen levels with coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; may increase corticosteroid levels when administered concurrently; use with hydantoins may cause spotting or breakthrough bleeding and reduce contraceptive effectiveness; increase in fluid retention caused by estrogen intake may reduce seizure control; antibiotics may alter GI flora and reduce absorption of oral contraceptives, which may reduce effectiveness

Contraindications

Documented hypersensitivity; endometrial and hepatic cancer; thromboembolic disorders; undiagnosed vaginal bleeding; smokers aged >35 y; cardiovascular disease, cerebral vascular, migraine with focal aura, known or suspected breast carcinoma, estrogen dependent neoplasia, or pregnancy; cholestatic jaundice of pregnancy or jaundice with previous use of pills, acute or chronic hepatocellular disease with abnormal liver function

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in patients with hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease

Medroxyprogesterone acetate (Cycrin, Provera)

No effect on androgen production. Progestins stop proliferation of endometrial cells, allowing organized sloughing of cells after withdrawal.

Dosing

Adult

10 mg PO qd for 10 d q2-3mo in amenorrhea or oligomenorrhea

Pediatric

Not established

Interactions

Aminoglutethimide may decrease effects by increasing hepatic metabolism of medroxyprogesterone

Contraindications

Documented hypersensitivity; cerebral apoplexy, undiagnosed vaginal bleeding, thrombophlebitis, and liver dysfunction

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in asthma, depression, renal or cardiac dysfunction, or thromboembolic disorders

Follow-up

Further Outpatient Care

• Patients need regular follow-up to prevent complications that may result from untreated PCOS.
• Participation in a peer support group may alleviate distress and improve self-management.³²

Complications

• Cardiovascular and cerebrovascular disease: Evidence suggest that these women might be at increased for cardiovascular disease and cerebrovascular disease.^33,34,35
• Type 2 diabetes mellitus: Patients with PCOS have an increased risk of developing diabetes mellitus.The American Association of Clinical Endocrinologists and the American College of Endocrinology recommend screening for diabetes by age 30 years in all patients with PCOS, including obese and nonobese women.¹⁶  In patients at particularly elevated risk, testing before the age of 30 years may be indicated. Patients who initially test negative for diabetes should be periodically reassessed throughout their lifetime.
  
  Patients should be screened for glucose intolerance with an 75-g OGTT. Measures to prevent diabetes should be adopted in patients who are found to have impaired glucose tolerance.
• Endometrial carcinoma: Patients with PCOS are at an increased risk for endometrial hyperplasia and carcinoma.³⁶ The chronic anovulation in PCOS leads to constant endometrial stimulation with estrogen and without progesterone and increases the risk of endometrial hyperplasia and carcinoma.

Patient Education

• PCOS is a disease with many long-term complications. Patients need regular follow-up with their physicians for early detection and management of any untoward sequelae associated with PCOS.
• For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education article Ovarian Cysts, Amenorrhea, and Female Sexual Problems.

Miscellaneous

Medicolegal Pitfalls

• Failure to diagnose the PCOS in a timely fashion can jeopardize the patient's health and expose her to complications such as increased morbidity and mortality from diabetes mellitus, endometrial carcinoma, and cardiovascular disease.

Special Concerns

• All other conditions that mimic PCOS should be ruled out before the diagnosis of PCOS is confirmed.
• Pregnancy must be ruled out before oral contraceptive therapy is started.
• The indications, contraindications, and adverse effects of metformin therapy should be carefully reviewed with the patient before such therapy is begun. In addition, women starting metformin therapy should be informed that such treatment may result in ovulatory menstrual cycles and increase the probability of pregnancy.
• Patients who are having difficulty conceiving should receive an adequate workup to rule out factors in them or their partner that might contribute to infertility.
• Women taking spironolactone require reliable contraception. An oral contraceptive is preferable; if oral contraception is contraindicated, they should practice another form of contraception.

References

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2. Stein IF. Duration of infertility following ovarian wedge resection. West J Surg. 1964;72:237.

3. Toulis KA, Goulis DG, Farmakiotis D, Georgopoulos NA, Katsikis I, Tarlatzis BC, et al. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update. May-Jun 2009;15(3):297-307. [Medline].

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5. 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.

6. Knochenhauer ES, Key TJ, Kahsar-Miller M, et al. Prevalence of the polycystic ovary syndrome in unselected black and white womenof the southeastern United States: a prospective study. J Clin Endocrinol Metab. Sep 1998;83(9):3078-82. [Medline].

7. Asuncion M, Calvo RM, San Millan JL, et al. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. Jul 2000;85(7):2434-8. [Medline].

8. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. Nov 1999;84(11):4006-11. [Medline].

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10. Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. Jan 1999;22(1):141-6. [Medline].

11. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. Jan 1999;84(1):165-9. [Medline].

12. Gopal M, Duntley S, Uhles M, Attarian H. The role of obesity in the increased prevalence of obstructive sleep apnea syndrome in patients with polycystic ovarian syndrome. Sleep Med. Sep 2002;3(5):401-4. [Medline].

13. Vgontzas AN, Legro RS, Bixler EO, et al. Polycystic ovary syndrome is associated with obstructive sleep apnea and daytimesleepiness: role of insulin resistance. J Clin Endocrinol Metab. Feb 2001;86(2):517-20. [Medline].

14. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. Jun 2004;89(6):2745-9. [Medline]. [Full Text].

15. PCOS Consensus Workshop Group. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. Jan 2004;81(1):19-25. [Medline].

16. American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists position statement on metabolic and cardiovascular consequences of polycystic ovary syndrome. National Guideline Clearinghouse. Available at http://www.guideline.gov/summary/summary.aspx?doc_id=7108&nbr=004279. Accessed August 28, 2009.

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Keywords

polycystic ovary syndrome, PCOS, polycystic ovarian disease, ovarian cysts, Stein-Leventhal syndrome, ovary disease, polycystic ovaries, hirsutism, amenorrhea, menstrual irregularity, hyperandrogenism, anovulation, obesity, insulin resistance, menstrual dysfunction, oligomenorrhea, clitoromegaly, infertility, male-pattern balding, alopecia, acanthosis nigricans

Contributor Information and Disclosures

Author

Mukhtar I Khan, MD, Assistant Professor of Medicine, Division of Endocrinology, Diabetes & Metabolism, SUNY Upstate Medical University, Syracuse, NY
Disclosure: Nothing to disclose.

Medical Editor

Jordan G Pritzker, MD, MBA, FACOG, Assistant Professor of Obstetrics, Gynecology, and Women's Health, Women's Comprehensive Health Center, Albert Einstein College of Medicine; Physician-In-Charge, Department of Obstetrics and Gynecology, Long Island Jewish Medical Center
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

A David Barnes, MD, PhD, MPH, FACOG, Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital, Mammoth Lakes, California, Pioneer Valley Hospital, Salt Lake City, Utah, Warren General Hospital, Warren, Pennsylvania and Mountain West Hospital, Tooele, Utah
A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association
Disclosure: Nothing to disclose.

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center
Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Chief Editor

Bryan D Cowan, MD, Professor and Chairman, Department of Obstetrics and Gynecology, University of Mississippi College of Medicine; Consulting Staff, Department of Obstetrics and Gynecology, Veterans Affairs Medical Center; Medical Director, Wiser Hospital for Women, University of Mississippi Medical Center
Bryan D Cowan, MD is a member of the following medical societies: American Association of Gynecologic Laparoscopists, American College of Obstetricians and Gynecologists, American Gynecological and Obstetrical Society, American Medical Association, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Endocrine Society, Sigma Xi, Society for Assisted Reproductive Technologies, Society for Gynecologic Investigation, Society for the Study of Reproduction, and Society of Laparoendoscopic Surgeons
Disclosure: Wyeth None Speaking and teaching

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