In a 22-year-old woman with facial hirsutism, weight gain, fatigue, irregular menstrual cycles, borderline pre-diabetic hemoglobin A1c, elevated DHEA‑Sulfate, high anti‑Müllerian hormone, and normal thyroid and prolactin levels, what is the most likely diagnosis and appropriate management?

Polycystic Ovary Syndrome (PCOS)

This 22-year-old woman has polycystic ovary syndrome (PCOS), confirmed by the presence of oligo-anovulation (irregular periods), biochemical hyperandrogenism (elevated DHEA-Sulfate 651 µg/dL), and elevated anti-Müllerian hormone (4.18 ng/mL) consistent with polycystic ovarian morphology. 1

Diagnostic Confirmation

Your patient meets the Rotterdam criteria for PCOS, which requires two of three features: oligo/anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology. 2 She clearly demonstrates:

• Menstrual irregularity indicating chronic anovulation 3
• Biochemical hyperandrogenism with DHEA-Sulfate elevated at 651 µg/dL (reference 110-431.7 µg/dL), which has 75% sensitivity and 67% specificity for PCOS 4
• Elevated AMH at 4.18 ng/mL, which strongly suggests polycystic ovarian morphology (threshold ≥5 ng/mL shows 92% sensitivity and 97% specificity) 1

Her total testosterone (56 ng/dL) and free testosterone (7.8 ng/dL) are within normal limits, but this does not exclude PCOS—total testosterone is abnormal in only 70% of confirmed PCOS cases. 1 The Rotterdam criteria explicitly allow diagnosis based on clinical hyperandrogenism (facial hirsutism) plus irregular cycles alone, without requiring abnormal testosterone levels. 1

The 17-OH progesterone of 209 ng/dL effectively excludes non-classical congenital adrenal hyperplasia (which typically shows values >200 ng/dL by some assays, though this is borderline and may warrant ACTH stimulation testing if clinical suspicion remains high). 4 Normal TSH (0.993 µIU/mL) and prolactin (12.0 ng/mL) exclude thyroid disease and hyperprolactinemia. 1

Critical Metabolic Assessment Already Completed

Your workup appropriately includes metabolic screening, which is mandatory in all PCOS patients regardless of fertility goals. 1

• Hemoglobin A1c 5.5% places her at the upper limit of normal (4.8-5.6%), confirming pre-diabetic status and warranting aggressive lifestyle intervention 4
• Lipid panel is currently normal (LDL 70 mg/dL, HDL 48 mg/dL, triglycerides 76 mg/dL), but annual monitoring is required because PCOS patients have disproportionately elevated cardiovascular risk 4
• BMI calculation and waist-hip ratio should be documented to assess central obesity, a key driver of insulin resistance in PCOS 1

Immediate Management Strategy

First-Line Therapy: Combined Oral Contraceptive Pills

Start combination oral contraceptive pills immediately as first-line therapy for menstrual irregularities, hirsutism, and endometrial protection. 4, 3 OCPs suppress ovarian androgen production, increase sex hormone-binding globulin (thereby reducing free testosterone), regulate menstrual cycles, and prevent endometrial hyperplasia from chronic unopposed estrogen exposure. 4 The risk of endometrial cancer is significantly elevated in PCOS due to chronic anovulation, obesity, and hyperinsulinemia. 4

Concurrent Metformin for Metabolic Management

Add metformin 850 mg three times daily (titrated gradually to minimize gastrointestinal side effects) to address insulin resistance, improve glucose tolerance, and reduce circulating androgens. 3 Metformin is beneficial for metabolic and glycemic abnormalities, improves menstrual irregularities, and promotes modest weight loss even in patients not seeking fertility. 4, 3 Given her pre-diabetic A1c of 5.5%, metformin provides dual benefit for both PCOS management and diabetes prevention. 4

Mandatory Lifestyle Intervention

Prescribe a multicomponent lifestyle program combining dietary modification, structured physical activity, and behavioral counseling—this is essential for all PCOS patients regardless of BMI because insulin resistance occurs independently of body weight. 3 Weight loss of as little as 5% of initial body weight improves metabolic and reproductive abnormalities in PCOS. 4 Even without weight loss, regular exercise has positive metabolic effects. 4

Hirsutism Management

The combination of an oral contraceptive plus an antiandrogen (spironolactone) is the most effective medical approach to hirsutism in PCOS. 4 Spironolactone can be added after 3-6 months if hirsutism does not improve adequately on OCPs alone. 4 Mechanical hair removal (laser vaporization, electrolysis) can be used adjunctively, but concomitant medical management is necessary because these methods do not address the underlying androgen excess. 4

Monitoring and Long-Term Surveillance

Repeat the following assessments every 6-12 months: 3

• 2-hour oral glucose tolerance test (75-gram glucose load) to screen for progression to type 2 diabetes 4, 1
• Fasting lipid profile (total cholesterol, LDL, HDL, triglycerides) to monitor cardiovascular risk 4, 3
• Blood pressure measurement to detect hypertension 3
• Body weight and BMI to track response to lifestyle intervention 3

Screen for psychological comorbidities (anxiety, depression, body-image concerns, eating disorders) at baseline and periodically, as these conditions are highly prevalent in PCOS. 3

Measure serum 25-hydroxy-vitamin D once to establish baseline status, as deficiency is present in 67-85% of PCOS patients. 3

Critical Pitfalls to Avoid

• Do not delay treatment waiting for ultrasound confirmation. Your patient already meets diagnostic criteria based on clinical and biochemical findings alone. 1 Ultrasound is not necessary when both irregular cycles and hyperandrogenism are present. 1

• Do not use AMH as a standalone diagnostic test. Although her AMH of 4.18 ng/mL is elevated and supports the diagnosis, AMH lacks standardization and validated cut-offs for clinical use. 1 It serves as supportive evidence but should not replace clinical judgment. 1

• Do not prescribe clomiphene citrate or other ovulation-induction agents unless she is actively attempting conception. 3 Her current presentation requires menstrual regulation and metabolic management, not fertility treatment. 3

• Do not ignore the elevated DHEA-Sulfate. While it confirms adrenal androgen excess typical of PCOS, values >3800 ng/mL in women aged 20-29 warrant consideration of non-classical congenital adrenal hyperplasia. 1 Her level of 651 µg/dL (approximately 6510 ng/mL if converted correctly) is significantly elevated and may warrant ACTH stimulation testing if the 17-OH progesterone remains borderline. 1

Long-Term Health Implications

Counsel this patient that PCOS confers lifelong increased risk for: 4, 5

• Type 2 diabetes mellitus and glucose intolerance
• Metabolic syndrome and hepatic steatosis
• Hypertension, dyslipidemia, and cardiovascular disease
• Endometrial hyperplasia and carcinoma (due to chronic unopposed estrogen)
• Subfertility and obstetric complications (if pregnancy is desired in the future)
• Mood disorders and psychosexual dysfunction

Emphasize that early intervention with lifestyle modification, OCPs, and metformin can significantly mitigate these risks and improve both metabolic and reproductive outcomes. 4, 3