Polycystic Ovarian Syndrome - PCOS

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)

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

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

• Irregular menses or amenorrhea
• Infertility
• Hirsutism, acne, male pattern baldness
  • Ferriman-Gallwey score – gold standard to measure hirsutism
    • Hirsutism defined by score ≥8
• High rate of diabetes mellitus (DM) type 2, metabolic syndrome, sleep apnea and obesity, which present increased risk for cardiovascular disease

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

• Late-onset CAH
• Androgen secreting tumors (ovarian, adrenal)
• Thyroid dysfunction
• Prolactinoma
• Pregnancy

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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
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

Diagnostic Algorithm

  Secondary Amenorrhea Testing Algorithm