Polycystic Ovary Syndrome - PCOS | Choose the Right Test

Medical Experts

Contributor

Doyle

Kelly Doyle, PhD, DABCC, FAACC

Associate Professor of Pathology (Clinical), University of Utah

Medical Director, Special Chemistry and Endocrinology, ARUP Laboratories

Contributor

Straseski

Joely A. Straseski, PhD, MS, MT(ASCP), DABCC, FAACC

Professor of Pathology (Clinical), University of Utah

Head of Clinical Operations for Clinical Chemistry, Toxicology, and Biochemical Genetics; Medical Director, Endocrinology; Co-Director, Automated Core Laboratory, ARUP Laboratories

Polycystic ovary syndrome (PCOS) is a common hormonal and metabolic disorder characterized by a combination of ovulatory dysfunction, clinical hyperandrogenism, biochemical hyperandrogenism (ie, hyperandrogenemia), and polycystic ovary morphology (PCOM). PCOS is a diagnosis of exclusion, and laboratory testing is required to rule out other potential etiologies. Testing may also be useful to assess for biochemical hyperandrogenism, ovulatory dysfunction, and/or PCOM when clinical evidence is not sufficient to issue a diagnosis.

Quick Answers for Clinicians

What testing should be used to diagnose polycystic ovary syndrome in adolescents?

Diagnostic testing for polycystic ovary syndrome (PCOS) is largely the same in adults and adolescents, except when assessment for polycystic ovary morphology (PCOM) is necessary for diagnosis. Currently, guidelines recommend against PCOM testing (ie, ultrasound and serum anti-Müllerian hormone testing) in adolescents.

Following the exclusion of other etiologies, evidence of both ovulatory dysfunction and hyperandrogenism is required to issue a PCOS diagnosis in adolescents. Laboratory testing for ovulatory dysfunction and biochemical hyperandrogenism may play a greater role if clinical evidence is lacking or indeterminate.

What testing should be used to diagnose polycystic ovary syndrome in menopausal and postmenopausal individuals?

Because changes in ovulation, hormone concentrations, and ovary morphology are typical in menopause, diagnosis of polycystic ovary syndrome (PCOS) in menopausal or postmenopausal individuals may need to be based on patient history and previous clinical or biochemical evidence (as detailed in the Clinical Assessment and Laboratory Testing sections). The Rotterdam criteria for diagnosis are recommended in postmenopausal adults. However, further investigation is needed to characterize the typical features and findings associated with menopausal/postmenopausal PCOS.

When polycystic ovary syndrome is suspected, what is the best test method for measuring testosterone levels?

In individuals without clinical signs of hyperandrogenemia (eg, hirsutism), assessment of free and total testosterone is recommended. Total testosterone should be tested by tandem mass spectrometry, whereas free testosterone can be evaluated by laboratory calculation.

Additional testing can be considered if testosterone concentrations are not found to be elevated; refer to Laboratory Testing for more details.

Can anti-Müllerian hormone testing be used to diagnose polycystic ovary syndrome in lieu of ovarian ultrasound?

Yes. Recent guidelines support the use of serum anti-Müllerian hormone (AMH) testing to evaluate for polycystic ovary morphology (PCOM) in adults when evidence of PCOM is needed for diagnosis of polycystic ovary syndrome (PCOS). Notably, evidence of PCOM is not required for diagnosis when two other diagnostic criteria for PCOS are met.

Guidelines recommend use of either serum AMH or ultrasound (not both) to evaluate for PCOM. In adolescents (defined as those fewer than 8 years postmenarche), testing for PCOM is not recommended, regardless of method.

How do hormonal contraceptives impact polycystic ovary syndrome testing?

Use of hormonal contraception impacts both sex hormone-binding globulin and gonadotropin-dependent androgen concentrations (the former is increased, whereas the latter is decreased). Hormonal contraceptives may also affect ovary morphology and anti-Müllerian hormone (AMH) concentrations. Therefore, assessment for biochemical hyperandrogenism should not occur until hormonal contraception has been discontinued for 3 months or more, and hormonal contraceptive use should be accounted for when assessing ovary morphology.

Indications for Testing

Evaluation for PCOS should be considered in adults presenting with hyperandrogenic features such as hirsutism, acne, and female pattern hair loss. Adults with signs of ovulatory dysfunction, such as irregular menstrual cycles, amenorrhea, or infertility, should also be evaluated.

In adolescents, hirsutism, severe acne, and irregular menstrual cycles (as defined by the latest international guideline on PCOS) may warrant further investigation.

PCOS Diagnostic Criteria

The Rotterdam criteria have been endorsed in the international evidence-based guideline on PCOS, with the caveat that in adolescents, criteria for both ovulatory dysfunction and hyperandrogenism should be met before a diagnosis is issued. The guideline also requires exclusion of nonclassical adrenal hyperplasia, thyroid disease, and hyperprolactinemia in all individuals, as well as other possible etiologies suggested by patient history and clinical presentation. See Exclusionary Testing for more information.

Rotterdam Criteria
At least 2 of the following: Oligoanovulation and/or anovulation Clinical and/or biochemical evidence of hyperandrogenism PCOM^a
^aPCOM assessment is not recommended in adolescents (ie, individuals <8 yrs postmenarche). Sources: Monash, 2023; Rotterdam, 2004

Rotterdam Criteria

At least 2 of the following:

Oligoanovulation and/or anovulation
Clinical and/or biochemical evidence of hyperandrogenism
PCOM^a

^aPCOM assessment is not recommended in adolescents (ie, individuals <8 yrs postmenarche).

Sources: Monash, 2023; Rotterdam, 2004

Clinical Assessment

Evaluation for PCOS should begin with a thorough patient history and clinical assessment. Refer to the following resources as applicable:

Modified Ferriman-Gallwey scoring system to evaluate hirsutism (a feature considered predictive of hyperandrogenemia)
Ludwig visual scoring system to evaluate hair loss
International evidence-based guideline on PCOS for criteria on menstrual irregularity in adults and adolescents

After initial evaluation, laboratory testing is required to exclude other etiologies and, when clinical evidence is inconclusive or incomplete, to confirm a diagnosis.

Laboratory Testing

Exclusionary Testing

Thyroid disease, hyperprolactinemia, and nonclassical congenital adrenal hyperplasia should be excluded in all individuals with suspected PCOS. Recommended laboratory testing for these conditions includes measurement of thyroid-stimulating hormone, prolactin, and serum 17-hydroxyprogesterone, respectively.

Testing to rule out other etiologies should be performed as needed based on patient history and the evolving clinical picture. Amenorrhea and more severe clinical manifestations (eg, overt virilization) should prompt further testing for etiologies such as hypogonadotropic hypogonadism, ovarian failure, Cushing disease, and androgen-secreting tumors.

Biochemical Hyperandrogenism

Although biochemical assessment for hyperandrogenemia is not always needed to diagnose PCOS, it may be helpful when clinical evidence is limited or indeterminate. The international guideline on PCOS recommends measurement of total testosterone and free testosterone to identify hyperandrogenemia. Total testosterone should be tested by tandem mass spectrometry, whereas free testosterone can be evaluated by laboratory calculation. Direct immunoassays are not recommended for testosterone testing as part of a PCOS workup.

If testosterone concentrations are within an average range, measurement of androstenedione and dehydroepiandrosterone sulfate (DHEAS) by tandem mass spectrometry can be considered, although these markers have decreased specificity compared with testosterone.

Ovulatory Dysfunction

In individuals with PCOS, ovulatory dysfunction (ie, oligoovulation or anovulation) may present with or without menstrual irregularity, although irregular menstrual cycles are common. When laboratory confirmation of ovulatory dysfunction is needed, serum progesterone testing should be performed during the midluteal phase of the menstrual cycle.

Polycystic Ovary Morphology

Assessment for PCOM is not required in individuals who meet other biochemical or clinical criteria for PCOS; however, it may be useful to confirm a PCOS diagnosis when only one other criterion has been met. Although ultrasound has long been the standard method to detect PCOM, recent guidelines now support the use of anti-Müllerian hormone (AMH) to detect PCOM in adults, given that it has been shown to strongly correlate with antral follicle count.

Importantly, serum AMH testing is not recommended in adolescents (defined by guidelines as individuals fewer than 8 years postmenarche) or in individuals already evaluated for PCOM by ultrasound. Furthermore, because specific AMH cutoff concentrations have not been broadly established, age, body mass index, contraceptive use, and menstrual cycle should be considered when testing, as these factors may affect circulating AMH.