What is the initial evaluation and management approach for a female patient of reproductive age presenting with irregular menses?

Initial Laboratory Evaluation for Irregular Menses

All reproductive-age women presenting with irregular menses require a pregnancy test first, followed by measurement of TSH, prolactin, FSH, LH, and consideration of additional hormonal testing based on clinical presentation. 1

Mandatory Initial Laboratory Tests

The following tests must be obtained in all patients with irregular menses:

• Pregnancy test (urine or serum β-hCG) - This is mandatory regardless of reported contraceptive use or sexual activity history, as pregnancy is the most common cause of amenorrhea 1, 2, 3, 4

• Thyroid-stimulating hormone (TSH) - Identifies thyroid dysfunction as a reversible cause, with elevated or suppressed levels indicating hypothyroidism or hyperthyroidism 1, 3, 4

• Prolactin - Elevated levels (>20 μg/L) suggest hyperprolactinemia, which may indicate pituitary adenoma or medication effect 1, 3, 4

• Follicle-stimulating hormone (FSH) - Elevated FSH (>40 mIU/mL) confirms primary ovarian insufficiency and requires repeat testing 4 weeks later for diagnosis 1, 3, 4

• Luteinizing hormone (LH) - An LH/FSH ratio >2 strongly suggests polycystic ovary syndrome (PCOS), while a ratio <1 is seen in approximately 82% of functional hypothalamic amenorrhea cases 1

Timing of Laboratory Testing

• Draw FSH, LH, and testosterone between cycle days 3-6 if the patient has any menstrual bleeding, or at any time in amenorrheic patients 1

• Progesterone should be measured mid-luteal phase (approximately day 21 of a 28-day cycle) to assess ovulatory status, with levels <6 nmol/L indicating anovulation 1

Additional Testing Based on Clinical Context

When Hyperandrogenism is Present (Hirsutism, Acne, Male-Pattern Hair Loss)

• Total testosterone and androstenedione - Testosterone >2.5 nmol/L suggests PCOS or valproate use 1

When Functional Hypothalamic Amenorrhea is Suspected (Low BMI, Athletes, Stress)

• Estradiol - Low levels indicate hypoestrogenism and support the diagnosis of functional hypothalamic amenorrhea 1

• Assessment for Female Athlete Triad/RED-S - Document weight changes, eating patterns, exercise habits, and consider bone mineral density testing via DXA in those with energy deficiency-related amenorrhea 1, 5

When Primary Ovarian Insufficiency is Confirmed (Elevated FSH)

• Karyotype testing if age <40 years to identify Turner syndrome or other chromosomal abnormalities 1, 3, 4

Physical Examination Priorities

Beyond laboratory testing, the clinical assessment should focus on:

• BMI calculation - Obesity is associated with PCOS and menstrual irregularities, while low BMI suggests hypothalamic amenorrhea 1, 5

• Clitoral size assessment - Width >10 mm after retracting the clitoral hood indicates elevated androgens from ovarian or adrenal pathology 6

• Galactorrhea evaluation - Presence suggests hyperprolactinemia 1

• Signs of hyperandrogenism - Hirsutism, acne, or male-pattern hair loss warrant androgen testing 1

Imaging Studies

• Pelvic ultrasonography is indicated when clinical features or hormonal tests suggest ovarian pathology, with transvaginal ultrasound being more sensitive than transabdominal for identifying structural abnormalities 1

• Endometrial thickness assessment via ultrasound helps differentiate conditions: thin endometrium (<5 mm) suggests estrogen deficiency, while thick endometrium (>8 mm) suggests chronic anovulation with unopposed estrogen 1

Critical Pitfalls to Avoid

• Do not assume chemotherapy-induced amenorrhea equals menopause - Hormone levels and absence of menses are unreliable indicators during tamoxifen treatment, and premenopausal estradiol levels can occur with transient chemotherapy-induced amenorrhea 1

• Do not misdiagnose functional hypothalamic amenorrhea with polycystic ovarian morphology (FHA-PCOM) as PCOS - FHA patients typically have low LH, low estradiol, thin endometrium (<5 mm), and LH/FSH ratio <1, despite ovarian appearance on ultrasound 1

• Do not skip endometrial evaluation in women >35 years - Endometrial biopsy should be performed before treatment initiation to exclude hyperplasia or malignancy in this age group with irregular menses 2

• Do not forget to document medication use - Antipsychotics, antiepileptics (especially valproate), and hormonal contraceptives can cause irregular menses 1