Polycystic ovarian syndrome (PCOS) is a common endocrinopathy caused by androgen excess and is the leading cause of anovulatory infertility. Because it is associated with increased cardiovascular risk as well as other adverse effects, diagnosis is essential for both treatment and monitoring reasons.
Diagnosis
Indications for Testing
Irregular menses, infertility, hirsutism, acne
Criteria for Diagnosis
Two of 3 of the following criteria in the absence of other etiology (American Association of Clinical Endocrinologists [AACE]/American College of Endocrinology [ACE]/Androgen Excess and Polycystic Ovarian Syndrome Society, 2015).
- Menstrual irregularities
- Hyperandrogenism (clinical or biological)
- Polycystic ovaries
Androgen Excess and PCOS Society Guidelines (developed in 2006, reaffirmed in 2015 [Goodwin, 2015]) |
Amsterdam European Society of Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine (ASRM) Consensus (3rd PCOS Consensus 2012) – reaffirmed use of Rotterdam 2003 criteria |
PCOS is a disorder of androgen excess or hyperandrogenism Diagnosis requires all 3 of the following elements
|
Adult female
Adolescent female
|
aHyperandrogenism
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Laboratory Testing
- Initial testing
- Serum free testosterone
- Mass spectrometry – gold standard
- Mass spectrometry with liquid chromatography (LC-MS/MS) – acceptable
- Radioimmunoassay (RIA) that includes purification – acceptable
- Assay that measures levels for females and children should be used
- Sample should be collected between day 4 and 10 of menstrual cycle
- Testosterone is elevated if >2.5 standard deviations above the mean
- Value >200 ng/dL should prompt evaluation for androgen-secreting tumor
- Testing should be performed by laboratories that use appropriate methods
- Serum free testosterone
- Additional testing
- Serum 17-hydroxyprogesterone
- Test for nonclassic 21-hydroxylase deficiency – patients with this deficiency will present with same clinical signs and symptoms as those with PCOS
- Anti-Mullerian hormone (AMH)
AMH Reference Intervals for Females Age Reference Interval (ng/mL) 6 mos-14 yrs
0.256-6.345
15-17 yrs
0.861-10.451
18-29 yrs
0.401-16.015
30-39 yrs
0.176-11.705
40-45 yrs
≤6.282
46-50 yrs
≤0.064
Postmenopausal
≤0.003
- AMH testing can be used in place of ovarian morphology assessment
- Progesterone
- Test midcycle to confirm anovulation
- Not required for diagnosis
- Serum 17-hydroxyprogesterone
- Other hormone testing not indicated
- Dehydroepiandrosterone (DHEA) – measurement does not add significantly to diagnosis
- 11β-hydroxyandrostenedione and androstenedione – generally not needed to assist with diagnosis
- Luteinizing hormone (LH)/follicle-stimulating hormone (FSH) – not indicated
Imaging Studies
- Transvaginal ultrasound
- Presence of polycystic ovaries alone is not sufficient to establish diagnosis
- Magnetic resonance imaging (MRI)/computed tomography (CT) – most useful to rule out adrenal/ovarian tumors if testosterone level is moderately elevated
Differential Diagnosis
- Pregnancy
- Measure beta human chorionic gonadotropin (β-hCG) level
- Adrenal hyperfunction (Cushing syndrome)
- Late onset congenital adrenal hyperplasia (CAH)
- Present in <5% of hyperandrogenic women
- Measure 17-hydroxyprogesterone
- Morning testing preferred
- If result is >200 ng/mL, further assessment is necessary to rule out CAH
- Androgen-secreting tumors (ovarian, adrenal)
- Present in 0.2% of hyperandrogenic women
- Testosterone >200 ng/dL combined with dehydroepiandrosterone sulfate (DHEA-S) >700 µg/dL suggests ovarian or adrenal tumor
- Metabolic syndrome
- Prolactinoma
- Measure prolactin
- Idiopathic hirsutism
- Acromegaly
- Thyroid dysfunction/hypothyroidism
- Measure thyroid-stimulating hormone (TSH)
- Drug related
- Testosterone
- Danazol
- Androgenic progestins
- Valproic acid
- Acetazolamide
- Minoxidil
- High-dose glucocorticosteroids
Monitoring
- Monitoring is recommended for long-term health consequences associated with polycystic ovarian syndrome (PCOS)
- Metabolic syndrome
- Cardiovascular disease
- Impaired glucose tolerance and diabetes
- Increased endometrial cancer risk
- Laboratory testing (after diagnosis) to evaluate for metabolic complications of PCOS
- Fasting 2-hour glucose tolerance test or hemoglobin A1c
- Fasting lipid profile (see Atherosclerotic Cardiovascular Disease [ASCVD] Risk Markers)
- Liver function testing (alanine aminotransferase, aspartate aminotransferase)
Background
Epidemiology
Prevalence – 10-15% of adult females worldwide (Azziz, Androgen Excess and Polycystic Ovarian Syndrome Society, 2009).
Genetics
- Family incidence nearly 40%
- Appears to be autosomal dominant
Pathophysiology
- Etiology is unknown
- Excess androgen production (hyperandrogenism) and insulin resistance play a role in disease pathogenesis
Clinical Presentation
- Irregular menses or amenorrhea
- Infertility
- Signs of hyperandrogenism, including
- Acne
- Hirsutism
- Increased number of terminal hairs
- Hatch modification of the Ferriman-Gallwey scale should be used to evaluate
- Alopecia – similar to male pattern baldness
- High rate of type 2 diabetes mellitus (T2DM), metabolic syndrome, sleep apnea, and obesity
Pediatrics
Epidemiology
- Prevalence – affects 5-10% of adolescent females
- 40% develop type 2 diabetes mellitus (T2DM) or impaired glucose tolerance by age 40
Clinical Presentation
- Hirsutism
- Increased number of terminal hairs
- Hatch modification of the Ferriman-Gallwey scale should be used to evaluate
- Ethnic differences affect hirsutism
- Alopecia – similar to male pattern baldness
- Acne – consider diagnosis of polycystic ovarian syndrome (PCOS) if acne is severe or does not respond to standard therapies
- Irregular menses of >2 years duration
- Obesity (central or refractory)
Indications for Testing
Irregular menses, hirsutism, acne, infertility
Laboratory Testing
- Initial testing
- Diagnosis may be more difficult in adolescents, but PCOS is important to be aware of and address early due to the risks associated with nontreatment
- Symptoms in patients <18 years may represent transient adolescent hormonal changes
- Serum or urine human chorionic gonadotropin (hCG) should be measured to rule out pregnancy
- Refer to main Laboratory Testing subsection within Diagnosis
- Refer to Secondary Amenorrhea Testing Algorithm
Imaging Studies
- Transvaginal ultrasound to evaluate ovaries
- Complicated by increased number of cysts normally occurring in adolescents
- Required by Amsterdam criteria, but not by Androgen Excess and Polycystic Ovarian Syndrome Society criteria
Differential Diagnosis
- Late-onset congenital adrenal hyperplasia (CAH)
- Androgen secreting tumors (ovarian, adrenal)
- Thyroid dysfunction
- Prolactinoma
- Pregnancy
ARUP Laboratory Tests
Provides a calculated value for free testosterone concentration using total testosterone measured by mass spectrometry
May be used to evaluate hyperandrogenism in children and cisgender females, monitor testosterone-suppressing hormone therapies (eg, antiandrogens or estrogens), evaluate testosterone status in individuals with protein-binding abnormalities, or evaluate hypogonadism in cisgender males
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry/Electrochemiluminescent Immunoassay/Calculation
Indicator of adrenal androgen production
Aids in the investigation of virilizing endocrinopathies in conjunction with other sex steroids
Not recommended for initial evaluation of polycystic ovarian syndrome (PCOS)
Quantitative Electrochemiluminescent Immunoassay
Not generally recommended
Adjunct tool for the evaluation of hirsutism
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Aids in the investigation of virilizing endocrinopathies and in managing congenital adrenal hyperplasia (CAH) in conjunction with other sex steroids
Not recommended for initial evaluation of PCOS
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Detect enzyme deficiencies causing CAH
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Screening for anterior pituitary tumor
Quantitative Chemiluminescent Immunoassay
Rule out Cushing syndrome
Quantitative Liquid Chromatography-Tandem Mass Spectrometry
Quantitative Enzyme Immunoassay
Assess thyroid function
Quantitative Electrochemiluminescent Immunoassay
Diagnose and manage diabetes mellitus (DM) and other carbohydrate metabolism disorders
Quantitative Enzymatic Assay
Assess cardiovascular disease risk and guide therapy
Quantitative Spectrophotometry/Quantitative Enzymatic Assay
Panel includes cholesterol, serum or plasma; triglycerides, serum or plasma; HDL cholesterol; LDL cholesterol, direct; VLDL, calculated; non-HDL cholesterol; appearance chemistry
Monitor liver function
Quantitative Enzymatic Assay
Quantitative Enzymatic Assay
Generally not used to contribute to polycystic ovarian syndrome (PCOS) diagnosis
Quantitative Electrochemiluminescent Immunoassay
Preferred test for screening and monitoring of thyroid function
Quantitative Chemiluminescent Immunoassay
Aids in detection and subclassification of hyperandrogenism
Most useful in women and children with moderate/severe hirsutism or hirsutism of any degree when it is sudden in onset or rapidly progressive
Hirsutism evaluation panel is generally preferred
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Panel includes androstenedione; dehydroepiandrosterone, serum or plasma; and testosterone (adult females, children, or individuals on testosterone-suppressing hormone therapy)
Aids in detection of nonclassical congenital adrenal hyperplasia (CAH) in individuals presenting with hyperandrogenism
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Panel includes androstenedione; 17-hydroxyprogesterone quantitative by HPLC-MS/MS, serum or plasma; testosterone (adult females, children, or individuals on testosterone-suppressing hormone therapy); and dehydroepiandrosterone, serum or plasma
Suitable for measurement of estradiol in adult premenopausal women
In all other groups, preferred test is estrogens, fractionated by tandem mass spectrometry (HPLC)
Quantitative Chemiluminescent Immunoassay
Aids in detection and subclassification of hyperandrogenism
Most useful in women and children with moderate/severe hirsutism or hirsutism of any degree when it is sudden in onset or rapidly progressive
Quantitative Chemiluminescent Immunoassay/Electrochemiluminescent Immunoassay/Liquid Chromatography-Tandem Mass Spectrometry
Panel includes androstenedione; dehydroepiandrosterone sulfate (DHEA-S), serum; testosterone, free (adult females, children, or individuals on testosterone-suppressing hormone therapy); testosterone (adult females, children, or individuals on testosterone-suppressing hormone therapy); and sex hormone-binding globulin
Adjunct test for the investigation of hyperandrogenic and adrenal disorders
Not recommended for initial evaluation of PCOS
Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Aids in the detection of insulinoma
Do not use to diagnose diabetes mellitus
Quantitative Chemiluminescent Immunoassay
References
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Azziz R, Carmina E, Dewailly D, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91(2):456-488.
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Medical Experts
Straseski

Reflex pattern: if the thyroid stimulating hormone is outside the reference interval, then free thyroxine (free T4) testing will be added