What is the initial workup for a patient presenting with irregular menstrual cycles?

Workup for Irregular Menstrual Cycles

The initial workup for irregular menstrual cycles should include comprehensive laboratory testing with hemoglobin, LH, FSH, prolactin, estradiol, thyroid function tests (T4, TSH), pregnancy test, and androgen profile, followed by pelvic ultrasound if clinical features or hormonal tests suggest ovarian pathology. 1

Laboratory Testing

Essential Initial Tests

• Pregnancy test (to rule out pregnancy as cause of missed periods)
• Complete blood count (to assess for anemia from heavy bleeding)
• Thyroid function tests (TSH, T4) (thyroid dysfunction can cause menstrual irregularities)
• Hormonal panel (should be performed between days 3-6 of cycle when possible):
  • FSH and LH (elevated FSH >35 IU/L suggests ovarian failure)
  • LH/FSH ratio (>2 suggests PCOS)
  • Prolactin (>20 μg/L suggests hyperprolactinemia)
  • Estradiol
  • Androgen profile (testosterone, DHEAS, androstenedione)

Additional Tests Based on Clinical Suspicion

• Fasting glucose/insulin (if PCOS or metabolic syndrome suspected)
• Progesterone (<6 nmol/L indicates anovulation)
• Anti-Müllerian hormone (AMH) (may be used as adjunctive test in women ≥25 years) 1

Imaging Studies

• Transvaginal ultrasound (preferred approach for evaluating ovarian morphology in sexually active patients)

  • Look for ≥20 follicles per ovary and/or ovarian volume ≥10ml using 8MHz frequency transducer
  • Assess endometrial thickness and rule out structural abnormalities 1

• Pelvic MRI (if ultrasound cannot adequately visualize the endometrium due to leiomyomas or adenomyosis) 2

• MRI with contrast (indicated if prolactin is elevated or multiple pituitary hormone abnormalities are present) 1

Endometrial Assessment

• Endometrial biopsy (indicated in cases of prolonged abnormal bleeding, especially in women >35 years or with risk factors for endometrial hyperplasia/cancer) 1

• Endometrial sampling should be considered if the patient has risk factors for endometrial cancer or if ultrasound cannot completely evaluate the endometrium 2

Diagnostic Considerations

Key Diagnostic Criteria

• Normal menstrual cycle: 21-35 days in length
• Irregular menstrual cycle: <21 days or >35 days, with abnormal flow 3
• PCOS diagnosis: LH/FSH ratio >2, elevated androgens, and polycystic ovaries on ultrasound 1
• Premature ovarian failure: Women <40 years with amenorrhea for ≥4 months, FSH >35-40 IU/L on two occasions at least one month apart, and estradiol <50 pmol/L 1
• Functional hypothalamic amenorrhea: Diagnosis of exclusion after ruling out other causes 1

Common Causes to Consider

• Pregnancy
• PCOS
• Thyroid dysfunction
• Hyperprolactinemia
• Premature ovarian insufficiency
• Hypothalamic dysfunction (stress, excessive exercise, weight changes)
• Structural abnormalities (fibroids, polyps, adenomyosis)
• Coagulopathies
• Endometrial pathology 2, 1

Important Clinical Considerations

• Irregular menstruation is associated with increased risk of metabolic syndrome, coronary heart disease, type 2 diabetes, and pregnancy complications 3, 4, 5

• Women with long or highly irregular menstrual cycles have significantly increased risk for developing type 2 diabetes (RR 2.08,95% CI 1.62-2.66) 4

• Irregular menstrual cycles before conception increase the risk of preeclampsia (7.9% vs. 5.2%) and low birthweight (6.0% vs. 3.6%) 5

• Hormone replacement therapy should be discontinued prior to laboratory evaluation to avoid false results 1

• If unexplained vaginal bleeding is present and pregnancy or underlying pathology is suspected, progestin-only contraceptives should be used with caution until evaluation is complete 2

Referral Indications

• Gynecology referral: Suspected anatomic abnormalities, persistent symptoms despite normal laboratory values, or desire for fertility assessment

• Endocrinology referral: Elevated FSH levels, suspected PCOS with metabolic concerns, or suspected chromosomal abnormalities 1

Follow-up Recommendations

• Reassess every 3 months
• Monitor bone health and metabolic parameters
• Annual screening for type 2 diabetes and cardiovascular risk assessment in women with PCOS
• Regular monitoring of androgen levels, menstrual cycle regularity, and symptoms of hyperandrogenism for PCOS management 1