Topic Editor: Sara Millican, MBBS
Review Date: 11/14/2012
Definition
Polycystic ovary syndrome (PCOS) is a common endocrine disorder of reproductive age women. It is characterized by irregular or absent menstrual periods, noncyclic gonadotropin secretion, and excessive androgen secretion.
Description
- PCOS is the most common endocrine disorder; its etiology is unknown
- PCOS is a complex disorder characterized by a state of chronic oligoovulation associated with functional androgen excess, involving signs of menstrual dysfunction, anovulation, and signs of hyperandrogenism
- PCOS affects reproductive, endocrine and metabolic systems and often leads to issues such as menstrual dysfunction, infertility, hirsutism, acne, obesity, or metabolic syndrome
- Symptoms of PCOS typically begin during puberty and progressively worsen
- There are no pathognomic features and it is largely a diagnosis of exclusion; several professional groups have proposed diagnostic criteria for PCOS
- The NIH consensus criteria encompasses the following minimal diagnostic criteria:
- Menstrual irregularity due to oligoovulation or anovulation
- Evidence of hyperandrogenism (clinical or biochemical)
- Exclusion of other causes of hyperandrogenism and menstrualirregularity
- The Rotterdam criteria encompass a broader spectrum of phenotypes; 2 of the following 3 are required for diagnosis:
- Oligoovulation and/or anovulation
- Clinical and/or biochemical signs of hyperandrogenism
- Polycystic ovaries (by ultrasound)
- Other common findings include infertility, obesity, oily skin, skin discoloration, elevated insulin levels, insulin resistance, high cholesterol levels, and elevated blood pressure
- PCOS is a leading cause of infertility, typically affecting women of reproductive age
Epidemiology
Incidence/Prevalence
- Nearly 1 in 15 women are affected by PCOS globally
- In the U.S., PCOS is a commonly occurring endocrine condition of women of reproductive age, with a prevalence of 4-12%
- Small preliminary studies have shown a higher incidence of PCOS in some ethnic subgroups such as Mexican-American and indigenous Australian women
Age
- Occurs in pre-menopausal women
- Onset may be perimenarchal but may not be identified until post menarche due to irregular menses
Genetics
- First-degree relatives of affected patients are more likely to develop the condition, indicating a genetic component
Risk factors
- Diabetes mellitus (both Type I and Type II are risk factors)
- Family history of hirsutism, menstrual disorders, PCOS, diabetes, infertility
- Hypertension
- Hyperandrogenism
- Obesity
- Ovarian hyperthecosis
- Premature adrenarche
Etiology
- The exact etiology of PCOS is unknown, but multiple genetic and environmental factors may contribute to its development
- PCOS is thought to be due to interplay between abnormalities of the hypothalamic-pituitary axis, increased androgen production by the ovaries and adrenal glands, and increased insulin resistance
- Studies have shown that women with a family history of polycystic ovaries are 50% more likely to develop PCOS
- Insulin resistance, hyperinsulinemia, obesity and high cholesterol may have an important role in development of abnormalities in the metabolism of androgens and estrogen, and in the control of androgen production
- Elevated insulin directly and indirectly stimulates ovarian androgen production in a genetically primed ovary
- Women who are overweight have a greater risk of developing PCOS as being overweight increases insulin production, which contributes to increased male hormone production and activity
- Abnormalities in the hypothalamic-pituitary axis may lead to increased amplitude and frequency of pulses of luteinizing hormone which may increase androgen production and lead to anovulation
- Family history of diabetes and high cholesterol may be additional contributing factors for PCOS
History
- Symptoms typically begin at the time of puberty and, in younger patients, and may be difficult to distinguish from irregular menses that are common during the year after menarche
- Patients may have a family history of PCOS, hirsutism, adrenal enzyme deficiencies, obesity, menstrual disorders, diabetes, and infertility
- Patients may present with menstrual abnormalities, history of menstrual disturbance, menstrual bleeding, oligomenorrhea, secondary amenorrhea, dysfunctional uterine bleeding, or history of infertility or subfertility
- Sleep apnea or somnolence
Physical findings on examination
- Acanthosis nigricans (dark, pigmented skin) may be seen in some women
- Features consistent with metabolic syndrome such as hypertension, obesity (BMI >30) and increased abdominal circumference >35 inches
- Hyperandrogenism - most commonly manifests as acne, excess body hair, often in a male distribution (e.g. upper lip, chin, around nipples), and male-pattern hair loss
- In extreme forms of hyperandrogenism alopecia, increased muscle mass, deepening voice, or clitoromegaly may be seen
- Ovaries may be enlarged in some cases
General treatment items
- As the exact etiology of PCOS is unknown, treatment should be aimed at the symptoms of the disorder, and preventing complications
- Depending on the needs of the patient, treatment should focus on either improvement of fertility and/or hyperandrogenism
- Therapeutic goals should include maintenance of a normal endometrium, antagonism of androgenic activity on target tissues, treatment of metabolic derangement, and correcting anovulation
- Behavior modification is recommended, and should include weight loss, diet, and exercise. The Androgen Excess and Polycystic Ovary Syndrome Society recommends that overweight and obese women with PCOS should be primarily managed with lifestyle modifications to address metabolic complications
- Weight reduction decreases serum androgen, insulin, and LH levels
- Weight loss of 2% to 5% in obese patients mayhelp restore ovulatory menstrual periods in up to 80% of overweight or obese patients
- In patients with type 2 diabetes mellitus, treatment with oral hypoglycemic agents,especially metformin, can effectively reduce androgens, improve insulin sensitivity, and aid weight loss
- PCOS patients planning for pregnancy should be managed by a reproductive endocrinologist or a primary care physician familiar with ovulation induction
- First-line agents for treating infertility and inducing ovulation include metformin and clomiphene alone or in combination
- Nonpharmacologic treatment options such as electrolysis, waxing, bleaching, plucking, depilatory creams, thermolysis, and laser therapy should be considered for treatment of hirsutism
- Antiandrogens (e.g., spironolactone and eflornithine) are effective pharmacological treatments for hirsutism
- Finasteride is effective for treatment of hirsutism (off label)
- Eflornithine can be used topically to slow hair growth
- First line therapyfor those not desiring concurrent fertility involves induction of regular menstrual cycles with administration of oral contraceptives
- An oral contraceptive containing ethinyl estradiol and a progestin with minimal androgenic activity, (eg, desogestrel) may be useful in reducing the free testosterone levels
- Gonadotropin-releasing hormone (GnRH) analogs (eg, leuprolide), may be used in women who do not respond to or cannot tolerate oral contraceptive pills
- Surgery
- Laparoscopic surgery, such as electrocautery, laser drilling, and multiple biopsy, may help restore fertility
- The primary aim of surgery is to restore ovulation
- Surgery is not often indicated or used given the number of pharmacological options available
Medications indicated with specific doses
Ovulation inducing agents
Hypoglycemic agentsAntiandrogens- Spironolactone
- Leuprolide [IM/SC]
- Finasteride
- Eflornithine [Topical]
- Desogestrel/ethinyl estradiol (monophasic OCP)
- Medroxyprogesterone [IM/SC]
Dietary or Activity restrictions
- Adequate diet control and regular exercise can reduce the risk of developing Type II diabetes mellitus
- Impaired glucose tolerance requires reduced carbohydrate intake to regulate insulin response
- Obese women should follow a low-calorie diet for weight reduction
- Patients with type 2 diabetes should have diet rich in fiber, low carbohydrates, trans fats, and saturated fats with increased omega-3 and omega-9 fatty acids
- Intake of omega-3 fatty acid has been shown to reduce liver fat content and other cardiovascular risk factors
- Women with dyslipidemia should follow a diet low in cholesterol and saturated fats, and increase physical activity
Prevention
- There are no proven primary prevention measures for PCOS (apart from maintaining an ideal body weight)
- Lifestyle modifications such as low calorie intake, weight loss, frequent exercise and healthy diet may be beneficial to prevent diabetes in PCOS; robust clinical evidence is lacking
Prognosis
- Long-term complications may include infertility, depression/anxiety, dyslipidemia, hypertension, type 2 diabetes mellitus, coronary artery disease, and endometrial cancer
- Early diagnosis and treatment are essential to reduce the risk for complications
- PCOS increases the risk for type 2 diabetes mellitus and consequent cardiovascular complications and cerebrovascular complications, particularly in women who develop insulin resistance
- Infertility has a favorable prognosis, however, some women may require assisted reproductive techniques for successful conception
Pregnancy/Pediatric affects on condition
- Adverse pregnancy outcomes in women with PCOS include increased incidence of gestational diabetes, pregnancy-induced hypertension, preeclampsia, preterm birth, vascular dysfunction, and fetal macrosomia
- Pregnant women with PCOS should be monitored carefully, and advised of the increased risk of maternal and fetal complications
Synonyms/Abbreviations
Synonyms
- Polycystic ovaries
- Polycystic ovary disease
- Polyfollicular ovarian disease
- Stein-Leventhal syndrome
Abbreviations
ICD-9-CM
ICD-10-CM
- E28.2 Polycystic ovarian syndrome
