What initial investigations should be ordered for a patient presenting with irregular menstruation?

Initial Investigations for Irregular Menstruation

The primary workup for irregular menstrual periods should include a pregnancy test, thyroid-stimulating hormone (TSH), prolactin levels, and assessment for polycystic ovary syndrome (PCOS), which is the most common cause of irregular menstruation in young adults. 1

Comprehensive Initial Evaluation

Medical History Assessment

• Detailed menstrual history:
  • Age of menarche
  • Regularity of menses (cycle length <21 or >35 days indicates irregularity)
  • Duration and amount of bleeding
  • Presence of intermenstrual bleeding
  • Medication use that could affect menstruation
  • Other health issues
  • Family menstrual history 1

Physical Examination

• BMI calculation
• Signs of hyperandrogenism (hirsutism, acne)
• Thyroid examination
• Abdominal/pelvic examination (if sexually active) 1

Essential Laboratory Tests

1. Pregnancy test - rule out pregnancy as a cause of missed periods 2, 1
2. Thyroid function tests:
   • TSH
   • Free T3 (fT3)
   • Free T4 (fT4) 1, 3
3. Prolactin level - elevated levels can cause amenorrhea 1, 4
4. Gonadotropins:
   • Follicle-stimulating hormone (FSH)
   • Luteinizing hormone (LH)
   • LH:FSH ratio (>2 suggests PCOS) 1
5. Sex hormones:
   • Estradiol
   • Testosterone (>2.5 nmol/l is abnormal)
   • Androstenedione (>10.0 nmol/l is abnormal)
   • DHEAS (Age 20-29 >3800 ng/ml, Age 30-39 >2700 ng/ml is abnormal) 1
6. Metabolic screening:
   • Fasting glucose
   • Insulin (glucose/insulin ratio >4 is abnormal) 1
7. Complete blood count - to assess for anemia, particularly with heavy bleeding 3

Additional Investigations Based on Initial Findings

For Suspected PCOS

• Pelvic ultrasound to evaluate for polycystic ovaries 1

For Suspected Thyroid Dysfunction

• Thyroid antibodies if autoimmune thyroiditis is suspected 3
• Thyroid ultrasound if structural abnormalities are suspected 3

For Suspected Hypothalamic Dysfunction

• Assessment of energy availability and nutritional status
• Screening for disordered eating or excessive exercise 1

For Suspected Pituitary Abnormalities

• Consider MRI of pituitary if prolactin is significantly elevated or if other pituitary hormone abnormalities are present 4

Important Clinical Considerations

• Hyperprolactinemia with thyroid dysfunction is a common contributory factor in patients with amenorrhea 4
• Hypothyroidism can shift the hemostatic system towards a hypocoagulable state, increasing bleeding risk 3
• Low energy availability can disrupt LH pulsatility and cause functional hypothalamic amenorrhea, particularly in athletes or those with recent weight changes 1
• Irregular menstruation may be associated with increased risk of metabolic syndrome, coronary heart disease, type 2 diabetes mellitus, and even ovarian cancer in later life 5, 6

Referral Criteria

• Gynecology referral for:

  • Suspected anatomic abnormalities
  • Persistent symptoms despite normal laboratory values
  • Desire for fertility assessment 1

• Endocrinology referral for:

  • Elevated FSH levels suggesting primary ovarian insufficiency
  • Suspected PCOS with metabolic concerns
  • Suspected chromosomal abnormalities 1

By following this systematic approach to investigating irregular menstruation, clinicians can identify the underlying cause and implement appropriate management strategies to improve patient outcomes and prevent long-term health complications.