Polycystic Ovarian Syndrome - PCOS

Primary Author Meikle, A. Wayne, MD.

Key Points

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. 

  • Androgen Excess Society Guidelines and Amsterdam ESHRE/ASRM Consensus (3rd PCOS Consensus 2010)
Androgen Excess Society Guidelines (2006)  − reaffirmed use of 1990 NIH criteria with some modifications
  • 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)
    • Exclusion of other androgen excess disorders
Amsterdam ESHRE/ASRM Consensus (3rd PCOS Consensus 2010) − reaffirmed use of Rotterdam 2003 criteria
  • 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 of age)
      • 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

Diagnosis

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 (testosterone should be >2.5 standard deviations above the mean for the assay)
      • 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 not 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  

Imaging Studies

  • Ultrasound to image polycystic ovaries (often unnecessary)
    • Presence of polycystic ovaries alone does not necessarily indicate PCOS
  • MRI/CT – if testosterone level is moderately elevated, use these images to rule out adrenal/ovarian tumors

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

Monitoring

  • Long-term health consequences associated with PCOS
  • 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)

Clinical Background

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

Epidemiology

  • Prevalence – 6-8% of adult females worldwide

Inheritance

  • Family incidence nears 40%
  • Appears to be autosomal dominant

Pathophysiology

  • Etiology is unknown
  • Excess androgen production (hyperandrogenism); often insulin resistance

Clinical Presentation

Pediatrics

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 of age may represent transient adolescent hormonal changes
    • Serum or urine hCG – rule out pregnancy
    • Serum free testosterone (use assay 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 – often not necessary
  • 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 not 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
      • If patient is overweight and meets criteria for metabolic syndrome – fasting blood glucose and fasting lipid panel 
  • Refer to Secondary Amenorrhea Testing Algorithm for additional diagnosis information

Imaging Studies

  • Ultrasound to image polycystic ovaries (required for Amsterdam criteria, but not Androgen Excess Society)

Differential Diagnosis

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
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.

Gold standard test; use to diagnose PCOS

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

   
Dehydroepiandrosterone Sulfate, Serum 0070040
Method: Quantitative Electrochemiluminescent Immunoassay

May aid in diagnosing PCOS (determine androgen excess in disorders of the adrenal cortex) but often of little clinical use

   
Androstanediol Glucuronide Quantitative 2005419
Method: Quantitative High Performance Liquid Chromatography/Tandem Mass Spectrometry

May aid in diagnosing PCOS but often of little clinical use

   
Androstenedione 2001638
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
May aid in diagnosing PCOS but often of little clinical use    
Luteinizing Hormone and Follicle Stimulating Hormone 0070193
Method: Quantitative Electrochemiluminescent Immunoassay

Generally not used to contribute to PCOS diagnose

   
17-Hydroxyprogesterone Quantitative by HPLC-MS/MS, Serum or Plasma 0092332
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry
Rule out late-onset CAH in evaluation for PCOS    
Cortisol Urine Free by LC-MS/MS 0097222
Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry

Rule out Cushing syndrome in evaluation for PCOS

   
Cortisol, Saliva 0081117
Method: Quantitative Enzyme Immunoassay

Rule out Cushing syndrome in evaluation for PCOS

   
Prolactin 0070115
Method: Quantitative Chemiluminescent Immunoassay

Rule out prolactin-secreting tumor in evaluation for PCOS

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

Rule out thyroid dysfunction in evaluation for PCOS

   
Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Monitor PCOS

Order for glucose:insulin ratio determination

Patient must be fasting  
Lipid Panel, Extended 0020468
Method: Quantitative Spectrophotometry/Quantitative Enzymatic

Monitor liver function in PCOS

Patient must be fasting

 
Aspartate Aminotransferase, Serum or Plasma 0020007
Method: Quantitative Enzymatic

Monitor liver function in PCOS

   
Alanine Aminotransferase, Serum or Plasma 0020008
Method: Quantitative Enzymatic

Monitor liver function in PCOS

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Thyroid Stimulating Hormone 0070145
Method: Quantitative Chemiluminescent Immunoassay
Virilization Panel 1 2002028
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Components include androstenedione; dehydroepiandrosterone, serum or plasma; and free testosterone, females or children

Virilization Panel 2 2002281
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Components include androstenedione; 17-hydroxyprogesterone quantitative by LC-MS/MS; testosterone, females or children; and dehydroepiandrosterone

Estradiol, Adult Premenopausal Female, Serum or Plasma 0070045
Method: Quantitative Chemiluminescent Immunoassay

Diagnose PCOS

Hirsutism Evaluation Panel 2001763
Method: Quantitative Chemiluminescent Immunoassay/Electrochemiluminescent Immunoassay/Liquid Chromatography-Tandem Mass Spectrometry
Dehydroepiandrosterone, Serum or Plasma 2001640
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry

Diagnose PCOS (determine androgen excess in disorders of the adrenal cortex)

Insulin, Fasting 0070063
Method: Quantitative Chemiluminescent Immunoassay