Polycystic Ovary Syndrome: Making the Diagnosis

SUMMARY: 

PCOS is a complex disorder characterized by varying degrees of ovulatory dysfunction, hyperandrogenism and metabolic disorders. It carries with it the risk of cardiovascular disease and diabetes, as well as endometrial cancer. An International Guideline for the diagnosis and management of polycystic ovary syndrome (PCOS) was released by the International PCOS Network (2023).   The guideline was developed with an international advisory panel 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, several European societies on reproductive health, and the ASRM. This guideline provides updated definitional criteria to make an accurate diagnosis.

Diagnostic Criteria 

The International Guideline Endorses the Rotterdam Criteria  

• The Rotterdam Criteria requires two out of three of the following (after other causes are excluded):
  • Clinical/biochemical signs of hyperandrogenism
  • Ovulatory dysfunction
  • Polycystic ovaries on ultrasound or elevated anti-mullerian hormone (AMH) levels

Note: If hyperandrogenism is present in the setting of irregular menses, ultrasound or AMH are not necessary  

• Adolescents   
  • Ultrasound and AMH are not recommended  
  • Adolescents with PCOS-like features not meeting diagnostic criteria should be considered at “increased risk” for PCOS 
    • Reassessment advised around 8 years post-menarche 
    • Applicable to those with PCOS features pre/post combined OCP use, persistent symptoms, or significant weight gain in adolescence 

Clinical Diagnosis 

Hyperandrogenism  

• Findings consistent with diagnosis of hyperandrogenism include
  • 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

Anovulation 

• Consider PCOS when irregular menstrual cycles are present
• 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 | Nonclassic congenital adrenal hyperplasia (CAH) can mimic PCOS 

Imaging  

Ultrasound and Polycystic Ovarian Morphology (PCOM) 

• Do not use for <8 years post menarche
• High incidence of multifollicular ovaries
• Transvaginal approach preferred
  • 8 MHz transducer
• Follicle number per ovary is the most effective sonographic marker for PCOS
• Threshold
  • ≥20 follicles/ovary and/or
  • Ovarian volume ≥10 ml in either ovary

Laboratory Diagnosis 

Androgens 

• Use one of the following
  • Total and Free testosterone
  • 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
• If androgen results are very high compared to lab reference ranges, consider neoplasia
• Routine screening for Cushing Syndrome in patients with hyperandrogenic chronic anovulation not indicated
  • Only screen if patients have coexisting signs
    • Buffalo hump | Abdominal Striae | Centripetal fat distribution | Hypertension

Note: Lab testing for hyperandrogenism most useful when clinical findings unclear or absent 

AMH 

• Should not be the only indicator of a PCOS diagnosis 
• Either AMH or ultrasound can be used to PCOM (polycystic ovarian morphology) 
• AMH should not be used in adolescents 
• Factors that influence AMH levels  
  • Peaks age 20 to 25 
  • Inversely proportional to maternal weight 
  • May be suppressed by recent combined oral contraceptive use 
  • Varies during the menstrual cycle 

Other Clinical Considerations at Time of Diagnosis  

Consider Patients at Increased Risk for Metabolic Syndrome  

• 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 

• Obesity
  • Weight reduction: 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 75 gram 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
• Recommend healthy lifestyle behaviors for all women with PCOS
  • Focus on healthy eating and physical activity.
  • Aims to improve general health, quality of life, body composition, and weight management.
  • Goals include maintaining weight, preventing weight gain, and achieving modest weight loss

Obstructive Sleep Apnea (OSA) 

• PCOS associated OSA independent of BMI 
• Screen with simple questionnaire (find more information in Related Topics below)  
• Definitive diagnosis via sleep study 

Endometrial Hyperplasia and Cancer Risk 

• PCOS is associated with higher risk for endometrial hyperplasia and cancer 
• Routine screening is not recommended as absolute risk is low  
• Prevention strategies 
  • Weight management 
  • Menstrual cycle regulation 
  • Progestogen therapy 
• If increased endometrial thickness, treat as per guidelines including biopsy and withdrawal bleeding  

Psychological Features 

• PCOS may be associated with the following  
  • Depression 
  • Altered body image 
  • Eating disorders 

Pregnancy Risks 

• Increased risk for  
  • Gestational diabetes 
  • Preterm birth 
  • Hypertension 
  • Cesarean delivery 
  • Growth restriction 
• No increased risk  
  • LGA infants 
  • Instrumental deliveries 
  • Macrosomia 

 Learn More – Primary Sources: 

Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome  

Monash University PCOS Program 

ACOG Practice Bulletin No 194: Polycystic ovary syndrome 

Screening and Diagnosis of Obstructive Sleep Apnea  – PcMED Project 

CMAJ Review: Diagnosis and management of polycystic ovarian syndrome