In a 26‑year‑old woman with irregular periods, active acne, luteinizing hormone 14 IU/L, follicle‑stimulating hormone 5.58 IU/L, low progesterone, normal 17‑hydroxy‑progesterone, mildly elevated prolactin, and a normal pelvic ultrasound, what is the most likely diagnosis and first‑line management?

Diagnosis: Polycystic Ovary Syndrome (PCOS)

This patient meets diagnostic criteria for PCOS based on the Rotterdam criteria, which requires two of three features: irregular periods (ovulatory dysfunction), active acne (clinical hyperandrogenism), and the elevated LH/FSH ratio of 2.5 supports the diagnosis. 1, 2

Diagnostic Confirmation

The diagnosis can be established without ultrasound findings because this patient has both irregular menstrual cycles AND clinical hyperandrogenism (acne), satisfying two Rotterdam criteria. 3 The normal pelvic ultrasound does not exclude PCOS, as polycystic ovarian morphology is only one of three criteria and is not mandatory when the other two are present. 3, 2

Supporting Laboratory Findings

• LH/FSH ratio of 2.5 (14/5.58) strongly supports PCOS, as ratios >2 are characteristic of the syndrome, though this finding is present in only 35-44% of PCOS patients. 3, 4
• Low progesterone (0.289) confirms anovulation, as mid-luteal progesterone <6 nmol/L indicates lack of ovulation. 3
• Mildly elevated prolactin (30.3) requires exclusion of hyperprolactinemia before finalizing the PCOS diagnosis, as prolactinomas can mimic PCOS with similar menstrual irregularity and acne. 5
• Normal 17-OH progesterone effectively excludes non-classical congenital adrenal hyperplasia, a key differential diagnosis. 1

Critical Exclusions Required

Before confirming PCOS, you must obtain TSH to exclude thyroid disease, as hypothyroidism causes menstrual dysfunction, weight gain, and can elevate androgen levels, perfectly mimicking PCOS. 3, 5 This is mandatory and non-negotiable. 5

Repeat prolactin measurement is essential because the current level of 30.3 is borderline elevated (normal <20 μg/L). 3 If confirmed elevated on repeat testing, pituitary imaging is required to exclude prolactinoma. 5

Missing Laboratory Tests

Total or free testosterone measurement by LC-MS/MS is the single most important missing test, with 74% sensitivity and 86% specificity for documenting biochemical hyperandrogenism. 3 While clinical hyperandrogenism (acne) alone is sufficient for diagnosis, biochemical confirmation strengthens the diagnosis and guides treatment intensity. 1, 3

A 2-hour oral glucose tolerance test with 75g glucose load is mandatory to screen for glucose intolerance and type 2 diabetes, as all women with PCOS have increased metabolic risk. 1, 3

Fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) is required to assess cardiovascular risk factors driven by insulin resistance. 3

First-Line Management

Hormonal Contraceptives

Combined oral contraceptives are the first-line treatment for both menstrual irregularities and acne in this patient. 1, 2 They address the two primary presenting complaints simultaneously by:

• Regulating menstrual cycles and preventing endometrial hyperplasia from unopposed estrogen 2
• Reducing ovarian androgen production and increasing sex hormone-binding globulin, thereby improving acne 2

Topical Acne Therapy

Combination therapy with topical retinoid plus benzoyl peroxide is recommended for the active acne, as combination therapy addressing multiple pathogenic factors is superior to monotherapy. 1 Topical dapsone 5% gel is specifically recommended for inflammatory acne in adult females. 1

Metabolic Intervention

Metformin should be initiated if glucose intolerance or insulin resistance is documented on the pending oral glucose tolerance test, as it improves menstrual irregularities and metabolic parameters. 2 However, metformin has limited benefit for acne treatment. 2

Weight management counseling is critical if BMI is elevated, as substantial weight loss (>15% body weight) can lead to significant improvement in PCOS symptoms. 6

Monitoring Protocol

Cardiovascular risk factors require monitoring every 6-12 months, including weight, blood pressure, and repeat metabolic screening. 3

Screen for depression and anxiety, as these are common comorbidities in PCOS that significantly impact quality of life. 6

Common Pitfalls to Avoid

Do not diagnose PCOS without first excluding hyperprolactinemia and thyroid disease, as these conditions are treatable mimics with entirely different management strategies. 5 Treating presumed PCOS without this exclusion results in treatment failure and delayed appropriate therapy. 5

Do not rely on ultrasound findings for diagnosis in this case, as 17-22% of asymptomatic women have polycystic ovarian morphology on ultrasound. 3 The clinical and biochemical features are sufficient. 3

Do not use AMH levels as a diagnostic test, as there is no validated cut-off and significant overlap exists between women with and without PCOS. 3

Do not prescribe topical antibiotics as monotherapy for acne due to bacterial resistance risk; always combine with benzoyl peroxide. 1