Polycystic Ovarian Syndrome - PCOS

Primary Author: Straseski, Joely A., PhD, MS, MT(ASCP), DABCC.
  • Key Points
  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics
  • Videos

Definitions of Polycystic Ovarian Syndrome (PCOS)

The etiology of PCOS remains unclear; variability of phenotype expression continues to present challenges for clinical care and research concerning this heterogenous condition. Two widely accepted and similar criteria used for defining PCOS exist.

CRITERIA FOR DEFINING PCOS

Androgen Excess Society Guidelines (2009) – reaffirmed use of 1990 NIH criteria with some modifications

Amsterdam ESHRE/ASRM Consensus (3rd PCOS Consensus 2012) – reaffirmed use of Rotterdam 2003 criteria
  • PCOS is a disorder of androgen excess or hyperandrogenism
    • All 3 elements confirm PCOS
    • Hyperandrogenism*
      • Clinical (hirsutism) and/or biochemical signs (elevated levels of total or free testosterone)
    • Ovarian dysfunction − oligoanovulation and/or polycystic ovaries (prominent but not universal feature of PCOS)
      • Polycystic ovarian morphology defined as per guidelines (Dewailey, 2014)
        •  ≥25 follicles/ovary – recommended over ovarian volume for criteria
        •  ≥10 ml ovarian volume
    •  Exclusion of other androgen excess disorders
  • Adult female
    • PCOS is a disorder of androgen excess or hyperandrogenism
    • Presence of 2 of 3 elements confirms PCOS
      • Hyperandrogenism*
        • Clinical (hirsutism) or biochemical signs
      • Oligo-ovulation and/or anovulation
      • Polycystic ovaries on ultrasound
        • Presence of ≥12 follicles in each ovary measuring 2-9 mm diameter and/or increased ovarian volume >10 cm3
    • Exclusion of other androgen excess disorders
  • Adolescent female
    • Risk of overdiagnoses of PCOS in this population
    • Diagnosis requires presence of all 3 elements to confirm PCOS
      • Oligomenorrhea or amenorrhea for ≥2 years after menarche (or primary amenorrhea at 16 years)
      • Polycystic ovaries on ultrasound (size >10 cm3)
      • Hyperandrogenemia

*Hyperandrogenism

  • Usually defined as >2.5 SD above mean for assay
  • Measure between 4th and 10th day of menstrual cycle
  • Lab testing to confirm
    • Testosterone is the hormone usually measured
      • May have poor validity in some labs
      • Assay should measure testosterone levels for female and children
    • Androstenedione and DHEA-S are informative markers but not necessary in most cases

Indications for Testing

  • Irregular menses, infertility, hirsutism, acne

Criteria for Diagnosis

Refer to Key Points tab

Laboratory Testing

  • Initial testing
    • Serum or urine hCG – rule out pregnancy
    • Serum free testosterone
      • Gold standard by mass spectrometry; single most important androgen measure
      • Use assay that measures levels for females and children
      • Usually elevated in polycystic ovarian syndrome (PCOS)
        • Testosterone should be >2.5 standard deviations above the mean for the assay to be deemed elevated
        • >200 value should prompt evaluation for androgen secreting tumor
      • May have poor validity in some laboratories
    • Dehydroepiandrosterone sulfate (DHEA-S), androstenedione and/or androstanediol glucuronide – usually unnecessary to make diagnosis of PCOS
      • Testosterone >200 ng/dL combined with DHEA-S >700 µg/dL suggest ovarian or adrenal tumor
    • Luteinizing hormone/follicle stimulating hormone (LH/FSH) levels
      • Do not contribute to PCOS diagnosis – typically LH is elevated and FSH is normal
      • LH/FSH ratio >2 suggestive of PCOS – should not be ordered as routine diagnostic tests for PCOS
  • Rule out the following (PCOS diagnosis involves exclusion of other etiologies)
    • Late onset CAH – 17-hydroxyprogesterone; morning testing preferred
      • If result is >200 ng/ml, referral is necessary to rule out CAH
    • Hyperprolactinemia – serum prolactin
    • Cushing syndrome – 24-hour urine cortisol or 2300 hours salivary cortisol; followup with overnight low-dose dexamethasone suppression testing
    • Hypothyroidism – thyroid-stimulating hormone
    •   Androgen secreting tumor
      • Testosterone >200 ng/dL combined with DHEA-S >700 µg/dL suggest ovarian or adrenal tumor

Imaging Studies

  • Ultrasound to image polycystic ovaries
    • Often unnecessary
    • Presence of polycystic ovaries alone does not necessarily indicate PCOS
  • MRI/CT – most useful to rule out adrenal/ovarian tumors if testosterone level is moderately elevated

Differential Diagnosis

  • Pregnancy
  • Cushing syndrome
  • Late onset congenital adrenal hyperplasia (CAH) (present in <5% of hyperandrogenic women)
  • Obesity
  • Androgen secreting tumors (ovarian, adrenal) (present in 0.2% of hyperandrogenic women)
  • Metabolic syndrome
  • Prolactinoma
  • Idiopathic hirsutism
  • Acromegaly
  • Thyroid dysfunction
  • Drugs
    • Testosterone
    • Danazol
    • Androgenic progestins
    • Valproic acid
    • Acetazolamide
    • Minoxidil
    • High-dose glucocorticosteroids
  • Long-term health consequences associated with PCOS require monitoring
  • Laboratory testing (after diagnosis) to evaluate for metabolic complications of PCOS
    • Fasting 2-hour glucose tolerance test
    • Fasting lipid profile
    • Liver function testing (alanine aminotransferase, aspartate aminotransferase)

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy caused by androgen excess and is the leading cause of anovulatory infertility.

Epidemiology

  • Prevalence – 10-15% of adult females worldwide (Androgen Excess, 2009)

Inheritance

  • Family incidence nears 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

Clinical Background

Epidemiology

  • Prevalence – affects 5-10% of adolescent females
  • 40% develop DM type 2 or impaired glucose tolerance by age 40

Clinical Presentation

  • Hirsutism
    • Moderate to severe – ≥8 on Ferriman-Gallwey scale
    • Male pattern baldness
  • Acne
  • Irregular menses >2 years duration
  • Obesity (central or refractory)

Diagnosis

Indications for Testing

  • Irregular menses, hirsutism, acne, infertility

Criteria for Diagnosis

Refer to Key Points tab

Laboratory Testing

  • Initial testing
    • Some recommendations suggest delaying diagnosis until 18 years
      • Symptoms in patients <18 years may represent transient adolescent hormonal changes
    • Serum or urine hCG – rule out pregnancy
    • Serum free testosterone (use assay designated for females and children) – single most important androgen measure
      • May have poor validity in some laboratories
    • Luteinizing hormone/follicle stimulating hormone (LH/FSH) – do not contribute to diagnosis (typically LH is elevated and FSH is normal)
    • DHEA-S – not necessary for most cases
  • Rule out the following (PCOS diagnosis involves exclusion of other etiologies)
    • Late-onset congenital adrenal hyperplasia (CAH) – 17-hydroxyprogesterone; morning testing preferred
      • If result is >200 ng/dL, referral is necessary to rule out CAH
    • Hyperprolactinemia – serum prolactin
    • Cushing syndrome – 24-hour urine cortisol or 2300 hour salivary cortisol; followup with overnight low-dose dexamethasone suppression testing
  • Refer to Secondary Amenorrhea Testing Algorithm for additional diagnostic information

Imaging Studies

  • Ultrasound to image ovaries
    • Required for Amsterdam criteria, but not for Androgen Excess Society

Differential Diagnosis

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Testosterone, Free and Total (Includes Sex Hormone Binding Globulin), Females or Children 0081056
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry/Electrochemiluminescent Immunoassay
The concentration of free testosterone is derived from a mathematical expression based on the constant for the binding of testosterone to sex hormone binding globulin.

Recommended Use 

Recommended initial test in the evaluation of suspected hyperandrogenemia in women and children

In patients with some menstrual cycling, sample should be drawn early in the follicular phase (day 4-10 of menstrual cycle); early morning (before 8:30 a.m.) is preferred

Very high levels (>200 ng/dL) suggest possibility of androgen-secreting tumor

Acceptable test for evaluating androgen deficiency in men

Dehydroepiandrosterone Sulfate, Serum 0070040
Method: Quantitative Electrochemiluminescent Immunoassay

Recommended Use 

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

Androstanediol Glucuronide Quantitative, Serum or Plasma 2005419
Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

Recommended Use 

Not generally recommended

Adjunct tool for the evaluation of hirsutism

Androstenedione 2001638
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use 

Aids in the investigation of virilizing endocrinopathies and in managing congenital adrenal hyperplasia in conjunction with other sex steroids

Not recommended for initial evaluation of polycystic ovarian syndrome

17-Hydroxyprogesterone Quantitative by HPLC-MS/MS, Serum or Plasma 0092332
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use 

Detect enzyme deficiencies causing CAH

Cortisol Urine Free by LC-MS/MS 0097222
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Recommended Use 

Rule out Cushing syndrome in evaluation for PCOS

Cortisol, Saliva 0081117
Method: Quantitative Enzyme Immunoassay

Recommended Use 

Rule out Cushing syndrome in evaluation for PCOS

Prolactin 0070115
Method: Quantitative Chemiluminescent Immunoassay

Recommended Use 

Screening for anterior pituitary  tumor in evaluation for PCOS

Thyroid Stimulating Hormone with reflex to Free Thyroxine 2006108
Method: Quantitative Electrochemiluminescent Immunoassay

Recommended Use 

Use to assess thyroid function

Use in risk stratification of palpable thyroid nodule

Thyroid stimulating hormone (TSH) status should be known to properly interpret serum thyroglobulin levels

Reflex pattern – if the Thyroid Stimulating Hormone is outside the reference interval, then Thyroxine, Free (Free T4) testing will be added

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Recommended Use 

Diagnose and manage DM and other carbohydrate metabolism disorders

Diagnosis of DM should be confirmed with a repeated test

Limitations 

Patient must be fasting

Lipid Panel, Extended 0020468
Method: Quantitative Spectrophotometry/Quantitative Enzymatic

Recommended Use 

Use to assess cardiovascular disease risk and guide therapy

Panel includes cholesterol, serum or plasma; triglycerides, serum or plasma; HDL cholesterol; LDL cholesterol, direct; VLDL, calculated; non-HDL cholesterol; appearance chemistry

Limitations 

Patient must be fasting

Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic

Recommended Use 

Monitor liver function

Alanine Aminotransferase, Serum or Plasma 0020008
Method: Quantitative Enzymatic

Recommended Use 

Monitor liver function

Guidelines

Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF, Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006; 91(11): 4237-45. PubMed

Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF, Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009; 91(2): 456-88. PubMed

Dewailly D, Lujan ME, Carmina E, Cedars MI, Laven J, Norman RJ, Escobar-Morreale HF. Definition and significance of polycystic ovarian morphology: a task force report from the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update. 2014; 20(3): 334-52. PubMed

Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Carmina E, Chang J, Yildiz BO, Laven JS, Boivin J, Petraglia F, Wijeyeratne CN, Norman RJ, Dunaif A, Franks S, Wild RA, Dumesic D, Barnhart K. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012; 97(1): 28-38.e25. PubMed

Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad H, Pasquali R, Welt CK, Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013; 98(12): 4565-92. PubMed

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004; 81(1): 19-25. PubMed

General References

Azziz R. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature. J Clin Endocrinol Metab. 2006; 91(3): 781-5. PubMed

Benjamins LJ, Barratt MS. Evaluation and management of polycystic ovary syndrome. J Pediatr Health Care. 2009; 23(5): 337-43. PubMed

Bruni V, Dei M, Nannini S, Balzi D, Nuvolone D. Polycystic ovary syndrome in adolescence. Ann N Y Acad Sci. 2010; 1205: 175-84. PubMed

Carmina E, Oberfield SE, Lobo RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol. 2010; 203(3): 201.e1-5. PubMed

Hassan A, Gordon CM. Polycystic ovary syndrome update in adolescence. Curr Opin Pediatr. 2007; 19(4): 389-97. PubMed

Lorenz LB, Wild RA. Polycystic ovarian syndrome: an evidence-based approach to evaluation and management of diabetes and cardiovascular risks for today's clinician. Clin Obstet Gynecol. 2007; 50(1): 226-43. PubMed

Setji TL, Brown AJ. Polycystic ovary syndrome: update on diagnosis and treatment. Am J Med. 2014; 127(10): 912-9. PubMed

Yii MF, Lim CE, Luo X, Wong WS, Cheng NC, Zhan X. Polycystic ovarian syndrome in adolescence. Gynecol Endocrinol. 2009; 25(10): 634-9. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Büttler RM, Martens F, Fanelli F, Pham HT, Kushnir MM, Janssen MJ, Owen L, Taylor AE, Soeborg T, Blankenstein MA, Heijboer AC. Comparison of 7 Published LC-MS/MS Methods for the Simultaneous Measurement of Testosterone, Androstenedione, and Dehydroepiandrosterone in Serum Clin Chem. 2015; 61(12): 1475-83. PubMed

Büttler RM, Martens F, Kushnir MM, Ackermans MT, Blankenstein MA, Heijboer AC. Simultaneous measurement of testosterone, androstenedione and dehydroepiandrosterone (DHEA) in serum and plasma using Isotope-Dilution 2-Dimension Ultra High Performance Liquid-Chromatography Tandem Mass Spectrometry (ID-LC-MS/MS) Clin Chim Acta. 2015; 438: 157-9. PubMed

Caanen MR, Kuijper EA, Hompes PG, Kushnir MM, Rockwood AL, Meikle WA, Homburg R, Lambalk CB. Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome. Eur J Endocrinol. 2016; 174(1): 25-32. PubMed

Moller AT, Backstrom T, et al. Diurnal Variations of Endogenous Steroids in the Follicular Phase of the Menstrual Cycle.. Neurochemistry & Neuropharmacology. [Published Feb 2016; Accessed: Apr 2017]

Ray JA, Kushnir MM, Rockwood AL, Meikle W. Direct Measurement of Free Estradiol in Human Serum and Plasma by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry. Methods Mol Biol. 2016; 1378: 99-108. PubMed

Medical Reviewers

Straseski, Joely A., PhD, MS, MT(ASCP), DABCC, Medical Director, Endocrinology at ARUP Laboratories; Assistant Professor of Clinical Pathology, University of Utah

Last Update: July 2017