Polycystic Ovary Syndrome: Making the Diagnosis

An International Guideline for the diagnosis and management of polycystic ovary syndrome (PCOS) was released by the International PCOS Network (2018).  The International Guideline committees included participants from 37 societies and organizations covering 71 countries.  The International Guideline was developed through the Centre for Research Excellence in Polycystic  Ovary Syndrome (CREPCOS), funded by the Australian National Health and Medical Research Council of Australia (NHMRC), in partnership with Monash University, ESHRE and the ASRM. This guideline provides needed definitional criteria to make an accurate diagnosis.

SUMMARY:

PCOS is a complex disorder characterized by varying degrees of ovulatory dysfunction, hyperandrogenism and metabolic disorders. It carries with it risk of cardiovascular disease and diabetes, as well as endometrial cancer.

KEY POINTS:

Diagnostic Criteria

The International Guideline Endorses the Rotterdam Criteria 

  • The Rotterdam Criteria requires two out of three of the following
    • Hyperandrogenism
    • Oligo or amenorrhea
    • Polycystic ovaries on ultrasound
  • Ultrasound not necessary for diagnosis when oligo/anovulation and hyperandrogenism present (however, will complete the phenotype)
  •  Adolescents
    • Both hyperandrogenism and oligo/anovulation must be present
    • Ultrasound not recommended

Diagnosing Hyperandrogenism

Clinical Diagnosis

  • History and physical exam findings of
    • Acne
    • Alopecia
    • Hirsutism
  • In adolescents, clinical findings must be severe
  • Reported unwanted excess hair growth and/or alopecia should be considered significant regardless of observed severity

Laboratory Diagnosis

  • Use one of the following
    • Free testosterone
    • Free androgen index
    • Calculated bioavailable testosterone
  • Consider androstenedione and dehydroepiandrosterone sulfate (DHEAS) if total or free testosterone are not elevated
    • Note that additional information provided will be limited
  • Lab tests for hyperandrogenism unreliable for women using hormonal contraception
    • If lab testing important/required, withdraw hormonal contraception for at least 3 months and use alternate contraceptive during that time
  • Lab testing for hyperandrogenism most useful when clinical findings unclear or absent
  • Routine screening for Cushing Syndrome in patients with hyperandrogenic chronic anovulation not indicated – should only occur if patients have coexisting signs
    • Buffalo hump | Abdominal Striae | Centripetal fat distribution | Hypertension
  • If androgen results are very high compared to lab reference ranges, consider neoplasia
  • The International Guideline recommends against  using AMH as a diagnostic marker for PCOS

Diagnosing Anovulation

  • When Irregular menstrual cycles are present, consider PCOS
  • Irregular Menses should be defined as follows
    • Normal if occurring in year 1 post menarche (considered part of pubertal transition)
    • 1 to <3 years post menarche: <21 or >45 days
    • 3 years post menarche to perimenopasuse: <21 days or  >35 days or <8 cycles per year
    • 1 year post menarche: >90 days for any one cycle
    • Primary amenorrhea: By age 15 or >3 years post thelarche (breast development)

Note: Ovulatory dysfunction can still occur with regular cycles. Confirm anovulation with serum progesterone levels

Ultrasound and Polycystic Ovarian Morphology

  • Do not use for <8 years post menarche
    • High incidence of multifollicular ovaries
  • Transvaginal approach preferred
    • 8 MHz transducer
  • Threshold (either ovary)
    • ≥20 follicles/ovary and/or
    • Ovarian volume ≥10 ml in either ovary

PCOS ICD10 Billing Code: E28.2

Other Diagnostic Considerations

Consider increased risk for metabolic syndrome and other causes of clinical findings  

  • Physical exam
    • Blood pressure | BMI | Waist circumference
  • Look for additional signs of hyperandrogenism and insulin resistance
    • Acne | Hirsutism | Male pattern hair growth | Acanthosis nigricans | Clitoromegaly
  • Laboratory (may be considered in addition to androgen levels depending on clinical scenario)
    • TSH | Prolactin | 17-OH progesterone
    • Consider screening for Cushing syndrome / acromegaly
    • 2-hour oral glucose tolerance test (fasting glucose, 75 g oral glucose load, 2 hour glucose level)
    • Fasting lipid and lipoprotein levels

Metabolic Syndrome Implications

  • Obese women with PCOS who reduce their weight by as little as 5% will have improved pregnancy rates, glucose and lipid levels and reduced hirsutism
  • Women with PCOS have a 2- to 5-fold increased risk of diabetes
    • Fasting glucose levels are poorly predictive of risk
    • The 2 hr glucose tolerance test above should be utilized instead
  • Screen women with PCOS for cardiovascular risk with BMI, fasting lipid and lipoprotein levels, metabolic syndrome risk factors
    • Rescreen periodically as impaired glucose tolerance can develop over time
    • Strongly recommend weight loss, if appropriate, and regular exercise

Note: Nonclassic congenital adrenal hyperplasia (CAH) can mimic PCOS

  • Endocrine testing for nonclassic CAH
    • Screen for CAH with a fasting level of 17-OH progesterone in the morning in the follicular phase
    • If 17-OH progesterone is elevated (normal < 2 ng/mL) follow with an adrenocorticotropic hormone (ACTH) stimulation test
  • Genetic testing for nonclassic CAH
    • CAH is caused by mutations in both copies of the  CYP21A2 gene that codes for the 21-hydroxylase enzyme
    • Hundreds of mutations have been reported, with 12 pathogenic variants account for >90% of cases
    • 3 mutations  (p.V281L, p.P453S, p.P30L) are associated with the milder, nonclassic form
    • Nonclassic CAH is less severe because 20-50% of enzyme activity is still present and symptoms in women are similar to PCOS

Learn More – Primary Sources:

Monash University PCOS Program

ACOG Practice Bulletin No 194: Polycystic ovary syndrome

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome

EJE: MANAGEMENT OF ENDOCRINE DISEASE: Morbidity in polycystic ovary syndrome

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME–PART 1

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME – PART 2