What are the next steps in testing for a 38-year-old female (F) with menstrual irregularities and a normal physical examination (PE)?

Initial Laboratory Workup for Menstrual Irregularities in a 38-Year-Old Woman

Begin with a comprehensive hormonal panel including thyroid function tests (TSH), prolactin, LH, FSH (measured on cycle days 3-6), and consider progesterone during mid-luteal phase to assess ovulation status. 1, 2

First-Line Laboratory Tests

The initial workup should systematically evaluate both structural and non-structural causes of menstrual irregularities:

Essential Hormonal Assessment

• Thyroid function tests (TSH): Thyroid dysfunction is a common reversible cause of menstrual irregularities and must be excluded first 1, 2

• Prolactin levels: Measure morning resting serum prolactin (>20 μg/L is abnormal); rule out hypothyroidism or pituitary tumor if elevated 1

• LH and FSH: Obtain serum levels on cycle days 3-6 of the menstrual cycle (calculate based on average of three estimations taken 20 minutes apart for accuracy) 1, 2

  • LH/FSH ratio >2 suggests PCOS (though less likely with elevated SHBG) 2
  • FSH >35 IU/L suggests premature ovarian failure 1
  • LH >11 IU/L or <7 IU/ml may indicate ovulatory dysfunction 1

• Mid-luteal progesterone: Measure during the mid-luteal phase according to menstrual cycle; levels <6 nmol/L indicate anovulation (common causes: PCOS, hypothalamic amenorrhea, hyperprolactinemia) 1

Androgen Assessment

• Total testosterone: Measure on cycle days 3-6; levels >2.5 nmol/L suggest hyperandrogenism (common causes: PCOS, valproate use, non-classical adrenal hyperplasia) 1, 2

• SHBG (Sex Hormone-Binding Globulin): Low SHBG may contribute to menstrual disturbance and can account for hirsutism even with normal testosterone levels 3

Additional Considerations

• Pregnancy test (beta-hCG): Always rule out pregnancy first, regardless of history 1

• Complete blood count: Assess for anemia if heavy bleeding is present 4

Imaging Studies

Transvaginal Ultrasound (First-Line Imaging)

• Indicated if: Clinical features or hormonal tests raise concern about ovarian pathology 1

• Transvaginal approach is preferred over transabdominal ultrasound for superior sensitivity in identifying structural abnormalities of the ovaries, including tumors and cystic changes 1

• Can evaluate for: Endometrial polyps, adenomyosis, leiomyomas, endometrial thickness, and polycystic ovarian morphology (>10 peripheral cysts of 2-8 mm diameter) 1, 2

• Limitations: Position of uterus, body habitus, and presence of uterine pathology can cause incomplete visualization 1

When Ultrasound is Insufficient

• MRI with diffusion-weighted imaging: Consider if the endometrium cannot be completely evaluated by ultrasound, especially in the presence of leiomyomas or adenomyosis, due to MRI's multiplanar capability and excellent tissue contrast resolution 1

• Pituitary MRI: Indicated if clinical features (galactorrhea) or laboratory results (hyperprolactinemia) suggest hypothalamic-pituitary axis abnormality 1

Endometrial Sampling Considerations

At age 38, endometrial sampling should be considered if:

• Risk factors for endometrial cancer are present (obesity, chronic anovulation, unopposed estrogen exposure) 1

• Ultrasound cannot adequately visualize the endometrium 1

• Medical treatment fails or bleeding persists despite initial management 1

Endometrial biopsy is preferred over dilation and curettage because it is less invasive, safer, and lower cost, though sensitivity can be affected by lesion type and size 1

Clinical Algorithm Summary

1. Confirm menstrual irregularity pattern using a menstrual chart for at least 6 months (polymenorrhea <23 days, oligomenorrhea >35 days, amenorrhea >6 months) 1

2. Rule out pregnancy with beta-hCG 1

3. Obtain hormonal panel: TSH, prolactin, LH, FSH (days 3-6), testosterone, mid-luteal progesterone 1, 2

4. Perform transvaginal ultrasound if hormonal abnormalities detected or to evaluate structural causes 1, 2

5. Consider endometrial sampling based on age, risk factors, and ultrasound findings 1

Referral Indications

• Endocrinology and/or gynecology referral if thyroid dysfunction confirmed, complex endocrine abnormalities found, or infertility is a concern (inability to conceive after 12 months of unprotected intercourse) 1, 2

• Hematology referral if heavy menstrual bleeding with flooding (changing pad/tampon more frequently than hourly), clots ≥1 inch diameter, or personal/family history of bleeding disorders 4

Common Pitfalls to Avoid

• Do not obtain prolactin levels post-ictally in patients with seizure disorders, as this will falsely elevate results 1

• Do not perform transvaginal ultrasound in virgins; use transabdominal approach instead 1

• Do not assume all irregularities are benign at age 38; this patient is approaching perimenopause but still requires thorough evaluation to exclude pathology 1

• Remember that medications (antiepileptics, hormonal contraceptives) can affect reproductive hormones and SHBG levels 1, 2