What is the evaluation and investigation approach for a 5-month missed menstrual period?

Evaluation and Investigation of a 5-Month Missed Menstrual Period

A 5-month missed menstrual period requires a systematic evaluation including pregnancy testing, hormone level assessment, and potentially imaging studies to identify the underlying cause, which may include polycystic ovary syndrome (PCOS), hypothalamic amenorrhea, hyperprolactinemia, or primary ovarian insufficiency.

Initial Assessment

History

• Obtain detailed menstrual history including previous regularity, last menstrual period, and any associated symptoms 1
• Assess for weight changes, exercise habits, stress levels, and dietary patterns 2
• Inquire about symptoms of hyperandrogenism (hirsutism, acne), galactorrhea, vasomotor symptoms, or thyroid dysfunction 1, 2
• Review medication use, including hormonal contraceptives 1
• Evaluate for chronic illness that might affect menstruation 2

Physical Examination

• Check vital signs including blood pressure and BMI 1
• Look for signs of hyperandrogenism (hirsutism, acne, male escutcheon) 1
• Assess for galactorrhea (breast milk expression in non-lactating women) 1
• Evaluate for signs of thyroid dysfunction 1
• Note body fat distribution (waist-to-hip ratio >0.9 suggests truncal obesity) 1

Laboratory Investigations

First-line Tests

• Pregnancy test (urine or serum) - must be performed first to rule out pregnancy 1
• Serum FSH and LH levels - ideally measured between days 3-6 of cycle if bleeding occurs; otherwise can be measured randomly 1, 2
• Serum prolactin level - measured in the morning at rest (not post-seizure) 1
• Thyroid-stimulating hormone (TSH) - to rule out thyroid dysfunction 2

Second-line Tests (based on initial results)

• Serum testosterone and androstenedione - if signs of hyperandrogenism are present 1
• Serum progesterone - during presumed mid-luteal phase to assess for ovulation 1
• Fasting glucose and insulin levels - especially if PCOS is suspected 1
• DHEAS (dehydroepiandrosterone sulfate) - if adrenal disorders are suspected 1
• Karyotype analysis - if primary ovarian insufficiency is suspected, especially in young patients 2

Imaging Studies

Pelvic Ultrasonography

• Indicated when clinical features or hormone tests suggest ovarian pathology 1
• Transvaginal ultrasound is preferred over transabdominal for better visualization 1
• Should be performed between days 3-9 of cycle if bleeding occurs 1
• Look for polycystic ovaries (>10 peripheral cysts 2-8mm in diameter, thickened ovarian stroma) 1

Additional Imaging

• Pituitary MRI - if hyperprolactinemia or other hypothalamic-pituitary abnormalities are suspected 1
• Note that small pituitary adenomas may be beyond MRI resolution 1

Differential Diagnosis and Specific Evaluations

PCOS (Polycystic Ovary Syndrome)

• Most common cause of secondary amenorrhea 1
• Diagnostic criteria: hyperandrogenic chronic anovulation 1
• Laboratory findings: LH/FSH ratio >2, elevated testosterone, insulin resistance 1
• Ultrasound findings: polycystic ovaries 1
• Affects 4-6% of general female population, but 10-25% of women with temporal lobe epilepsy 1

Hypothalamic Amenorrhea

• Associated with weight loss, excessive exercise, or emotional stress 3
• Laboratory findings: low LH (<7 IU/ml), low estradiol 1
• Evaluate for disordered eating patterns and low bone density 2
• Affects approximately 1.5% of general population but up to 12% of women with temporal lobe epilepsy 1

Hyperprolactinemia

• Check for medications that may elevate prolactin levels 1
• Evaluate for symptoms of galactorrhea 1
• Prolactin >20 μg/L is considered abnormal 1

Primary Ovarian Insufficiency

• Laboratory findings: FSH >35 IU/L 1
• May occur earlier in women with epilepsy than in general population 1
• Note that patients can maintain unpredictable ovarian function 2

When to Refer

Referral to Gynecology/Endocrinology is indicated for:

• Confirmed amenorrhea of >6 months 1
• Abnormal hormone levels suggesting specific pathology 1
• Signs of hyperandrogenism with menstrual irregularity 1
• Suspected structural abnormalities on imaging 1

Common Pitfalls and Caveats

• Don't assume infertility in patients with primary ovarian insufficiency, as they may maintain unpredictable ovarian function 2
• Isolated polycystic ovaries (without symptoms or hormonal abnormalities) are found in 17-22% of women and should not be confused with PCOS 1
• Hormone replacement therapy should be discontinued prior to laboratory evaluation to avoid interference with test results 1
• Anti-Müllerian hormone (AMH) is not recommended as the primary surveillance modality for evaluation of premature ovarian insufficiency 1
• Remember that irregular menstruation is associated with increased risk of metabolic syndrome, coronary heart disease, type 2 diabetes, and adverse pregnancy outcomes 4

By following this systematic approach, the underlying cause of a 5-month missed period can usually be identified and appropriate treatment initiated.