What is the diagnostic approach for a female patient of reproductive age presenting with unilateral polycystic ovary syndrome (PCOS)?

Diagnostic Approach for Unilateral Polycystic Ovary

True unilateral polycystic ovary morphology does not exist as a diagnostic entity for PCOS—the diagnosis requires assessment of both ovaries, and finding polycystic features in only one ovary should prompt investigation for alternative pathology rather than confirming PCOS.

Understanding the Diagnostic Framework

PCOS diagnosis requires meeting at least two of three Rotterdam criteria: hyperandrogenism (clinical or biochemical), ovulatory dysfunction, and polycystic ovarian morphology—but critically, the ovarian morphology criterion applies to the overall ovarian assessment, not individual ovaries 1, 2. When only one ovary demonstrates polycystic features, this represents an atypical presentation that warrants further investigation.

Initial Diagnostic Evaluation

Hormonal Assessment

• Measure total testosterone or free/bioavailable testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which demonstrates 92% specificity compared to 78% for direct immunoassays 1, 2
• Obtain sex hormone-binding globulin (SHBG) to calculate free androgen index 1
• Check androstenedione if levels exceed 10.0 nmol/L to exclude adrenal or ovarian tumors 1
• Measure DHEAS with age-specific thresholds: >3800 ng/mL for ages 20-29, >2700 ng/mL for ages 30-39 to exclude non-classical congenital adrenal hyperplasia 1
• Obtain TSH to exclude thyroid disease and prolactin (morning resting levels) to exclude hyperprolactinemia, with levels >20 μg/L being abnormal 1, 2
• Measure 17-hydroxyprogesterone to exclude non-classical congenital adrenal hyperplasia 1, 2

Menstrual History Documentation

• Document cycle length, with cycles >35 days suggesting chronic anovulation 3
• Obtain mid-luteal phase progesterone (day 21 of 28-day cycle or 7 days before expected menses) where levels <6 nmol/L indicate anovulation 1
• Assess onset and duration of symptoms—gradual onset suggests PCOS while rapid onset with marked virilization (testosterone typically >2.5 nmol/L) requires immediate evaluation for androgen-secreting tumors 1, 3

Critical Imaging Considerations for Unilateral Findings

Ultrasound Protocol

• Perform transvaginal ultrasound using transducers with frequency ≥8 MHz, evaluating for ≥20 follicles (2-9mm diameter) per ovary and/or ovarian volume ≥10 mL 1, 2
• Document three dimensions of each ovary separately and calculate volumes for both ovaries 3
• Ensure no corpus luteum, cyst, or dominant follicle is present, as these can confound interpretation 2
• If transvaginal approach is not feasible, use transabdominal ultrasound focusing on ovarian volume with threshold ≥10 mL 1, 2

When Unilateral Polycystic Morphology is Found

This finding should raise suspicion for alternative diagnoses rather than confirming PCOS. Consider:

• Ovarian tumors: Rapid onset of symptoms with testosterone >2.5 nmol/L warrants imaging for androgen-secreting tumors 1, 3
• Functional ovarian cysts: May mimic polycystic appearance on one side 4
• Technical limitations: Inadequate visualization of one ovary may create false impression of unilateral disease 4
• MRI pelvis without contrast should be obtained when ovaries cannot be adequately visualized by ultrasound or when unilateral findings are unexplained 1, 3

Metabolic Evaluation (Regardless of Ovarian Findings)

• Perform 2-hour oral glucose tolerance test with 75g glucose load in all women with suspected PCOS regardless of BMI, as insulin resistance occurs independently of body weight 1, 2
• Calculate fasting glucose/insulin ratio, where ratio >4 suggests reduced insulin sensitivity 1
• Obtain fasting lipid profile to assess cardiovascular risk 1, 2

Physical Examination Specifics

• Calculate BMI and waist-to-hip ratio (WHR >0.9 indicates truncal obesity) 1, 2
• Examine for acanthosis nigricans on neck, axillae, under breasts, and vulva indicating insulin resistance 1, 2
• Assess hirsutism using Ferriman-Gallwey scoring, evaluate for acne, male-pattern alopecia, and clitoromegaly 1, 3
• Screen for Cushing's syndrome signs (buffalo hump, moon facies, abdominal striae) and consider dexamethasone suppression test if present 1, 2

Common Diagnostic Pitfalls

• Polycystic ovarian morphology alone is insufficient for diagnosis, as PCOM may be present in up to one-third of reproductive-aged women without PCOS 3
• Serum AMH levels should not be used as a single test for PCOS diagnosis despite emerging evidence 2, 3
• Ultrasound should not be used for diagnosis in adolescents with gynecological age <8 years due to high incidence of physiologically normal multifollicular ovaries 2
• Age and BMI do not substantially affect diagnostic accuracy of follicle number per ovary or ovarian volume in the reproductive age range studied 5

Algorithmic Approach to Unilateral Findings

1. Confirm adequate bilateral ovarian visualization with high-frequency transvaginal ultrasound (≥8 MHz) 1
2. If only one ovary shows polycystic morphology: Obtain MRI pelvis to better characterize both ovaries and exclude masses 1, 3
3. If hormonal evaluation shows marked hyperandrogenism (testosterone >2.5 nmol/L, DHEAS significantly elevated): Pursue imaging for androgen-secreting tumors 1
4. If patient meets two other Rotterdam criteria (hyperandrogenism + ovulatory dysfunction): PCOS diagnosis can be made without relying on ovarian morphology 2
5. If unilateral finding persists with normal contralateral ovary and no other PCOS criteria met: This is not PCOS—consider alternative diagnoses 2, 4