Polycystic ovary syndrome ( PCOS ) is an endocrine disorder that affects approximately 5% of all women. It occurs amongst all races and nationalities, is the most common hormonal disorder among women of reproductive age (12-45years old), and is a leading cause of infertility.
The principal features are obesity, anovulation (resulting in irregular menstruation), acne, and excessive amounts or effects of androgenic (masculinizing) hormones. The symptoms and severity of the syndrome vary greatly among women. While the causes are unknown, insulin resistance, diabetes, and obesity are all strongly correlated with PCOS.
Nomenclature
Other names for this syndrome include polycystic ovary disease ( PCOD ), functional ovarian hyperandrogenism , Stein-Leventhal syndrome (original name, not used in modern literature), ovarian hyperthecosis and sclerocystic ovary syndrome .
Definition
Two definitions are commonly used:
- In 1990 a consensus workshop sponsored by the NIH/NICHD suggested that a patient has PCOS if she has all of:
- signs of androgen excess (clinical or biochemical),
- oligoovulation,
- other entities are excluded that would cause polycystic ovaries.
- In 2003 a consensus workshop sponsored by ESHRE/ASRM in Rotterdam indicated PCOS to be present if 2 out of 3 criteria are met:
- oligoovulation and/or anovulation,
- excess androgen activity,
- polycystic ovaries (by gynecologic ultrasound), and other endocrine disorders are excluded.
The Rotterdam definition is wider, including many more patients, notably patients without androgen excess, whereas in the NIH/NICHD definition androgen excess is a prerequisite. Critics maintain that findings obtained from the study of patients with androgen excess cannot necessarily be extrapolated to patients without androgen excess.
Symptoms
Common symptoms of PCOS include
- Oligomenorrhea, amenorrhea — irregular, few, or absent menstrual periods.
- Infertility, generally resulting from chronic anovulation (lack of ovulation).
- Hirsutism — excessive and increased body hair, typically in a male pattern affecting face, chest and legs.
- Hair loss appearing as thinning hair on the top of the head
- Acne, oily skin, seborrhea.
- Obesity or weight gain: one in two women with PCOS are obese.
- Depression.
- Deepening of voice
Mild symptoms of hyperandrogenism, such as acne or hyperseborrhea, are frequent in adolescent girls and are often associated with irregular menstrual cycles. In most instances, these symptoms are transient and only reflect the immaturity of the hypothalamic-pituitary-ovarian axis during the first years following menarche.
PCOS can present in any age during the reproductive years. Due to its often vague presentation it can take years to reach a diagnosis.
Risks
Women with PCOS are at risk for the following:
- Endometrial hyperplasia and endometrial cancer (cancer of the uterine lining) are possible, due to overaccumulation of uterine lining, and also lack of progesterone resulting in prolonged stimulation of uterine cells by estrogen. It is however unclear if this risk is directly due to the syndrome or from the associated obesity, hyperinsulinemia, and hyperandrogenism.
- Insulin resistance/Type II diabetes
- High blood pressure
- Dyslipidemia (disorders of lipid metabolism — cholesterol and triglycerides)
- Cardiovascular disease
- Strokes
- Weight gain
- Miscarriage
- Acanthosis nigricans (patches of darkened skin under the arms, in the groin area, on the back of the neck)
- Autoimmune thyroiditis
Diagnosis
Not all women with PCOS have polycystic ovaries (PCO), nor do all women with ovarian cysts have PCOS; although a pelvic ultrasound is a major diagnostic tool, it is not the only one. The diagnosis is straightforward using the Rotterdam criteria, even when the syndrome is associated with a wide range of symptoms.
- Standard diagnostic assessments:
- History-taking, specifically for menstrual pattern, obesity, hirsutism, and the absence of breast discharge. A clinical prediction rule found that these four questions can diagnose PCOS with a sensitivity of 77.1% (95% CI 62.7%–88.0%) and a specificity of 93.8% (95% CI 82.8%–98.7%).
- Gynecologic ultrasonography, specifically looking for small ovarian follicles. These are believed to be the result of disturbed ovarian function with failed ovulation, reflected by the infrequent or absent menstruation that is typical of the condition. In normal menstrual cycle, one egg is released from a dominant follicle - essentially a cyst that bursts to release the egg. After ovulation the follicle remnant is transformed into a progesterone producing corpus luteum, which shrinks and disappears after approximately 12–14 days. In PCOS, there is a so called "follicular arrest", i.e., several follicles develop to a size of 5-7 mm, but not further. No single follicle reach the preovulatory size (16 mm or more). According to the Rotterdam criteria, 12 or more small follicles should be seen in a ovary on ultrasound examination. The follicles may be oriented in the periphery, giving the appearance of a 'string of pearls'. The numerous follicles contribute to the increased size of the ovaries, that is, 1.5 to 3 times larger than normal.
- Laparoscopic examination may reveal a thickened, smooth, pearl-white outer surface of the ovary. (This would usually be an incidental finding if laparoscopy were performed for some other reason, as it would not be routine to examine the ovaries in this way to confirm a diagnosis of PCOS).
- Serum (blood) levels of androgens (male hormones), including androstenedione, testosterone and Dehydroepiandrosterone sulfate may be elevated. The free testosterone level is thought to be the best measure. The Free androgen index of the ratio of testosterone to sex hormone-binding globulin (SHBG), is meant to be a predictor of free testosterone, but is a poor parameter for this and is no better that testosterone alone as a marker for PCOS, possibly because FAI is correlated with the degree of obesity.
- Some other blood tests are suggestive but not diagnostic. The ratio of LH (Luteinizing hormone) to FSH (Follicle stimulating hormone) is greater than 1:1, as tested on Day 3 of the menstrual cycle. The pattern is not very specific and was present in less than 50% in one study. There are often low levels of sex hormone binding globulin, particularly among obese women.
- Common assessments for associated conditions or risks
- Fasting biochemical screen and lipid profile
- 2-hour oral glucose tolerance test (GTT) in patients with risk factors (obesity, family history, history of gestational diabetes) and may indicate impaired glucose tolerance (insulin resistance) in 15-30% of women with PCOS. Frank diabetes can be seen in 65–68% of women with this condition. Insulin resistance can be observed in both normal weight and overweight patients.
- For exclusion of other disorders that may cause similar symptoms:
- Prolactin to rule out hyperprolactinemia
- TSH to rule out hypothyroidism
- 17-hydroxyprogesterone to rule out 21-hydroxylase deficiency (CAH). Many such women may appear similar to PCOS and be made worse by insulin resistance or obesity, but they can be greatly helped by adrenal suppression with low-dose glucocorticoid therapy.
- Fasting insulin level or GTT with insulin levels (also called IGTT). Elevated insulin levels have been helpful to predict response to medication and may indicate women who will need higher dosages of metformin or the use of a second medication to significantly lower insulin levels. Elevated blood sugar and insulin values do not predict who responds to an insulin-lowering medication, low-glycemic diet, and exercise. Many women with normal levels may benefit from combination therapy. A hypoglycemic response in which the two-hour insulin level is higher and the blood sugar lower than fasting is consistent with insulin resistance. A mathematical derivation known as the HOMAI, calculated from the fasting values in glucose and insulin concentrations, allows a direct and moderately accurate measure of insulin sensitivity (glucose-level x insulin-level/22.5).
- Glucose tolerance testing (GTT) instead of fasting glucose can increase diagnosis of increased glucose tolerance and frank diabetes among patients with PCOS according to a prospective controlled trial. While fasting glucose levels may remain within normal limits, oral glucose tests revealed that up to 38% of asymptomatic women with PCOS (versus 8.5% in the general population) actually had impaired glucose tolerance, 7.5% of those with frank diabetes according to ADA guidelines.
Differential diagnosis
Other causes of irregular or absent menstruation and hirsutism, such as congenital adrenal hyperplasia, Cushing's syndrome, hyperprolactinemia, androgen secreting neoplasms, and other pituitary or adrenal disorders, should be investigated. PCOS has been reported in other insulin resistant situations such as acromegaly.
Pathogenesis
Polycystic ovaries develop when the ovaries are stimulated to produce excessive amounts of male hormones (androgens), particularly testosterone, either t
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