Polycystic Ovarian Syndrome Workup

Updated: Sep 19, 2019
  • Author: Richard Scott Lucidi, MD, FACOG; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Approach Considerations

The diagnosis of polycystic ovarian syndrome (PCOS) requires the exclusion of all other disorders that can result in menstrual irregularity and hyperandrogenism, including adrenal or ovarian tumors, thyroid dysfunction, congenital adrenal hyperplasia, hyperprolactinemia, acromegaly, and Cushing syndrome. [3, 4, 5] Biochemical and/or imaging studies must be done to rule out these other possible disorders and ascertain the diagnosis. A karyotype usually excludes mosaic Turner syndrome as a cause of the primary amenorrhea.

The Royal College of Obstetricians and Gynaecologists (RCOG) recommends the following baseline screening tests for women with suspected polycystic ovarian syndrome (PCOS): thyroid function tests, serum prolactin levels, and a free androgen index (defined as total testosterone divided by sex hormone binding globulin [SHBG] × 100, to give a calculated free testosterone level). [5]

Patients who are having difficulty conceiving should receive an adequate workup, along with their partners, to rule out factors that might contribute to infertility.

Samples for laboratory studies should be drawn early in the morning, with the patient in a fasting state; in women with regular menses, samples should be taken between days 5 and 9 of the menstrual cycle. [37] A serum human chorionic gonadotropin (hCG) level should be checked to rule out pregnancy in women with oligomenorrhea or amenorrhea.


Screening Laboratory Studies

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—measured 60 minutes after cosyntropin stimulation—rules out late-onset congenital adrenal hyperplasia.

Women with PCOS should be screened for Cushing syndrome or acromegaly only if there is a clinical suspicion of these conditions. 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 times the upper limit of normal are diagnostic for Cushing syndrome. [46] An overnight dexamethasone suppression test is also useful for screening for Cushing syndrome.

A serum insulin-like growth factor (IGF) ̶ 1 level should be checked to rule out acromegaly. Serum IGF-1 is a sensitive and specific marker of growth hormone (GH) excess. Normal levels rule out GH excess.

A small percentage of patients with PCOS have elevated prolactin levels (typically >25 mg/dL). Hyperprolactinemia can be excluded by checking a fasting serum prolactin concentration.


Hormone Levels


Androgen excess can be tested by measuring total 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 polycystic ovarian syndrome (PCOS). levels of sex hormone–binding globulin (SHBG) are usually low in patients with PCOS.

Androstenedione levels are also elevated in women with PCOS. This androgen precursor is 60% ovarian and 40% adrenal in derivation.

Patients with androgen-secreting ovarian or adrenal tumors can present with hirsutism, amenorrhea, and signs of virilization. Although the clinical picture of symptom onset and progression is more predictive than androgen levels, their testosterone level may be greater than 150 ng/dL and their DHEA-S level may be above 800 mcg/dL. DHEA-S is derived from the adrenal gland, and therefore, elevation of DHEA-S would be suggestive of an adrenal origin.

Follicle-stimulating hormone and luteinizing hormone levels

The follicle-stimulating hormone (FSH) level should be checked to rule out primary ovarian failure. In patients with PCOS, FSH levels are within the reference range or low. Luteinizing hormone (LH) levels are elevated for Tanner stage, sex, and age. The LH-to-FSH ratio is usually greater than 3.

Stimulation testing with a long-acting gonadotropin-releasing hormone (GnRH) agonist induces a characteristic rise in ovarian-derived 17-hydroxyprogesterone after 24 hours. This is thought to be a result of excessive 17-hydroxylase activity.

Thyroid-stimulating hormone and free thyroxine levels

Thyroid dysfunction, rather than PCOS, may be the source of amenorrhea and hirsutism. (In patients with PCOS, thyroid function tests are within the reference range.)

Long-standing primary hypothyroidism can be associated with a markedly elevated circulating thyroid-stimulating hormone (TSH) level. Elevated alpha subunit delivery (from one half of the dimeric TSH molecule) can then cross-react with FSH and LH receptors on breast tissue, leading to premature thelarche and, on ovarian tissue, resulting in a PCOS–like picture. These physical findings of the van Wyk-Grumbach syndrome (ie, juvenile hypothyroidism, precocious puberty, and ovarian enlargement) resolve upon thyroxine replacement therapy.


Glucose, Insulin, and Lipids

Because the prevalence of impaired glucose tolerance and type 2 diabetes mellitus is high in women with polycystic ovarian syndrome (PCOS)—particularly those who have a body mass index (BMI) greater than 30 kg/m2, have a strong family history of type 2 diabetes, or are older than 40 years—a 75-g oral glucose-tolerance test (OGTT) should 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. [47]

Women diagnosed with prepregnancy PCOS should be screened for gestational diabetes before 20 weeks’ gestation. [5] These women have a higher rate of gestational diabetes than women in the general population; therefore, refer them for expert obstetric diabetic consultation if abnormal results are found.

Some women with PCOS have insulin resistance and an abnormal lipid profile (cholesterol >200 mg/dL; LDL >160 mg/dL). Approximately one third of women with PCOS who are overweight have impaired glucose tolerance or type 2 diabetes mellitus by 30 years of age. [48]

A study concluded that insulin resistance and inflammatory markers may help identify adolescent girls with PCOS who are at the highest risk of developing the metabolic syndrome. [49] Metabolic heterogeneity also exists in women with PCOS according to phenotypic subgroup, with metabolic dysfunction confined to the subgroup with both oligomenorrhea and hyperandrogenic features. [50]


Imaging for PCOS


Ovarian ultrasonography, preferably accomplished by using a transvaginal approach, can be performed to assess ovarian morphology. Perform ultrasonography if the pelvic examination is inadequate, the patient has abdominal pain, testosterone levels are unusually high (eg, >200 ng/dL), it is needed to support the diagnostic criteria, or the patient is amenorrheic (to assess the endometrial thickness and exclude anatomic causes of amenorrhea). (See the image below.)

Longitudinal transabdominal ultrasonogram of an ov Longitudinal transabdominal ultrasonogram of an ovary. This image reveals multiple peripheral follicles.

CT scan and MRI

If a tumor is suspected, obtain a computed tomography (CT) scan or magnetic resonance image (MRI) to visualize the adrenals and ovaries. MRI is an excellent method for imaging the ovaries and is a useful alternative in very obese women in whom the ovaries might not be visualized with transvaginal ultrasonography (TVUS) and in those patients in whom TVUS is inappropriate, such as adolescent girls.


Histologic Findings

In polycystic ovarian syndrome (PCOS), histologic changes of the ovary include enlarged, sclerotic, multiple cystic follicles (see the image below). As previously stated, a woman is diagnosed with polycystic ovaries (as opposed to PCOS) if she has 20 or more follicles in at least 1 ovary, measuring 2-9 mm in diameter, or a total ovarian volume greater than 10 cm3. [1]

Low power, H and E of an ovary containing multiple Low power, H and E of an ovary containing multiple cystic follicles in a patient with PCOS.