What is the role of Anti-Mullerian Hormone (AMH) testing in the diagnosis of Polycystic Ovary Syndrome (PCOS)?

Role of AMH Testing in PCOS Diagnosis

AMH testing should not yet be used as a standalone diagnostic criterion for PCOS, but it can serve as a valuable adjunctive marker when ultrasound is unavailable, unacceptable, or technically limited. 1

Current Guideline Position

The Endocrine Society explicitly recommends that AMH should not replace the established Rotterdam diagnostic criteria (requiring 2 of 3: oligoanovulation, hyperandrogenism, polycystic ovaries on ultrasound). 1 This conservative stance reflects several unresolved technical and clinical challenges that must be addressed before AMH can be incorporated into routine diagnostic algorithms.

When AMH Testing May Be Clinically Useful

Despite not being a formal diagnostic criterion, AMH measurement has practical value in specific clinical scenarios:

• When ultrasound is unavailable or technically inadequate - AMH can indicate polycystic ovarian morphology when reliable ultrasonography data cannot be obtained. 2

• When transvaginal ultrasound is unacceptable to the patient - Some women find transvaginal ultrasound invasive or culturally unacceptable. 3

• When typical clinical findings are ambiguous - In women with hyperandrogenism or oligo-anovulation but unclear ultrasound findings, elevated AMH supports the diagnosis. 2

• For metabolic risk stratification - High AMH levels correlate with worse clinical, endocrinological, and metabolic parameters in PCOS, helping predict treatment response and long-term outcomes. 4

Diagnostic Performance

AMH demonstrates strong diagnostic accuracy when evaluated as an isolated marker:

• Sensitivity: 80-91.45% and specificity: 89.8-90.71% for PCOS diagnosis 2, 4

• Area under ROC curve: 0.916, indicating excellent discriminatory ability 2

• Optimal cutoff: 3.94-6.06 ng/mL depending on the study population and assay used 2, 4

• Mean AMH levels are 3-fold higher in PCOS (7.34 ng/mL) compared to controls (2.24 ng/mL) 2

Critical Limitations Preventing Routine Use

Assay Standardization Issues

• No international reference standard exists for AMH measurement, leading to significant inter-assay variability. 3, 1

• Older assays (DSL, IOT) are no longer marketed, and concordance between old and new automated platforms is problematic. 3

• Sample handling, transport, and storage conditions significantly affect results but are under-reported in the literature. 3

Age-Specific Challenges

• AMH should NOT be used in adolescents within 8 years of menarche due to significant overlap between PCOS and normal physiological values. 1, 3

• Age-specific reference ranges are essential but not yet established, as AMH levels naturally decline with age and are elevated in adolescence. 3, 1

• The sensitivity and specificity of AMH are lower in adolescents than adults, limiting diagnostic utility in younger populations. 3

Biological Variability

• Cut-off values have been inappropriately defined using the 95th percentile rather than clustering with other PCOS features or prediction of long-term health outcomes. 3

• AMH varies across the lifespan, with high levels in adolescence that overlap considerably with controls, making differentiation difficult. 3

• Relationship to long-term health outcomes (fertility, metabolic complications) requires further research before establishing biologically meaningful cut-offs. 3

Practical Clinical Algorithm

When considering AMH testing in suspected PCOS:

1. First, establish presence of oligoanovulation (menstrual cycles >35 days) and hyperandrogenism (clinical hirsutism or biochemical elevation of total testosterone, free testosterone, or androstenedione). 1, 5

2. Attempt ultrasound evaluation if patient is >8 years post-menarche and transvaginal approach is acceptable, using ≥8 MHz transducer to count follicles (FNPO ≥20 is diagnostic). 5

3. Consider AMH testing if:

   • Ultrasound is unavailable, technically inadequate, or unacceptable to patient
   • Patient already meets 2 Rotterdam criteria and you need additional supportive evidence
   • You need to assess metabolic risk stratification

4. Interpret AMH >4-6 ng/mL as supportive of PCOS diagnosis when combined with other criteria, but never as standalone evidence. 2, 4

5. Always perform metabolic screening (2-hour oral glucose tolerance test, fasting lipid profile) in women with elevated AMH and suspected PCOS. 1

Common Pitfalls to Avoid

• Do not use AMH as a standalone diagnostic test - it must be interpreted in context of Rotterdam criteria. 1

• Do not order AMH in adolescents <8 years post-menarche - rely on hyperandrogenism plus menstrual irregularity instead. 3, 1

• Do not assume all AMH assays are equivalent - results may vary significantly between platforms. 3

• Do not use arbitrary percentile cut-offs - clinical context and clustering with other PCOS features matter more than statistical thresholds. 3

Research Gaps Requiring Resolution

Before AMH can be formally incorporated into diagnostic criteria, the following must be addressed:

• International assay standardization with robust independent evaluation of commercial platforms 3

• Large population-based studies establishing age-specific reference ranges across the lifespan 3

• Clustering analysis of AMH with other PCOS features (hirsutism, hyperandrogenism, oligo-anovulation) 3

• Long-term outcome studies linking AMH levels to fertility, metabolic complications, and cardiovascular risk 3

Once these issues are resolved, AMH could potentially replace ultrasound as a more accessible, less costly, and less operator-dependent diagnostic criterion. 3 Until then, it remains a valuable adjunctive tool rather than a formal diagnostic criterion.