What is the next step for a premenopausal woman with an endometrial thickness of 1.4 centimeters and a last menstrual period (LMP) about six weeks ago?

Premenopausal Endometrial Thickness of 1.4 cm with 6-Week Amenorrhea

First Priority: Rule Out Pregnancy

The immediate next step is to obtain a quantitative serum β-hCG to exclude pregnancy, as an endometrial thickness of 14 mm with 6 weeks of amenorrhea is highly suggestive of early intrauterine pregnancy.

• A 6-week amenorrhea (from last menstrual period) with endometrial thickness of 14 mm is the classic presentation of early pregnancy, where the gestational sac and decidualized endometrium appear as thickened endometrium on ultrasound
• If pregnancy is confirmed, appropriate obstetric management should follow
• If β-hCG is negative, proceed with evaluation for pathologic endometrial thickening

If Pregnancy is Excluded: Endometrial Sampling is Required

For a premenopausal woman with endometrial thickness exceeding 11 mm, endometrial tissue sampling is mandatory to rule out hyperplasia or malignancy. 1

Rationale for Intervention Threshold

• The American College of Obstetricians and Gynecologists recommends endometrial biopsy for women with endometrial thickness exceeding 11 mm, as this represents a significant risk factor for endometrial hyperplasia or malignancy 1
• In premenopausal women without vaginal bleeding, an endometrial thickness >11 mm carries approximately 6.7% risk of cancer, whereas thickness ≤11 mm carries only 0.002% risk 2
• An endometrial thickness of 14 mm significantly exceeds the 11 mm threshold, warranting tissue diagnosis 1

Diagnostic Algorithm

Step 1: Office-Based Endometrial Sampling

• Perform endometrial biopsy using Pipelle or Vabra device, which have sensitivities of 99.6% and 97.1% respectively for detecting endometrial carcinoma 3
• This can be done as an outpatient procedure 1

Step 2: If Initial Sampling is Inadequate or Inconclusive

• Proceed to sonohysterography to distinguish between focal lesions (polyps, submucous fibroids) versus diffuse pathology 1
• Sonohysterography has 96-100% sensitivity for assessing endometrial pathology 1
• Consider hysteroscopy with directed biopsy for direct visualization and targeted sampling, especially if focal lesions are suspected 1

Step 3: If Office Sampling Fails

• Proceed to fractional dilation and curettage under anesthesia, which provides diagnosis in 95% of cases 1

Important Clinical Caveats

Common Pitfall to Avoid

• Do not rely solely on a negative outpatient Pipelle biopsy with this degree of endometrial thickening - office-based sampling has approximately 10% false-negative rate and is only useful if positive 3, 1
• If initial sampling is negative but endometrial thickness remains 14 mm, more extensive sampling or hysteroscopy with directed biopsies is required 1

Differential Diagnosis to Consider

• Early pregnancy (most likely given amenorrhea)
• Endometrial hyperplasia (with or without atypia)
• Endometrial polyp 1
• Submucous fibroid 1
• Endometrial carcinoma (though less common in premenopausal women) 3
• Anovulatory cycles with unopposed estrogen stimulation

Additional Imaging Considerations

• Complete pelvic assessment with both transvaginal and transabdominal ultrasound to evaluate for other pelvic pathology 1
• Color and spectral Doppler evaluation of internal vascularity can help identify abnormal vascular patterns 1

Management Based on Pathology Results

If Hyperplasia Without Atypia:

• Consider levonorgestrel intrauterine device (LNG-IUD) as first-line treatment, which provides local progestin delivery with minimal systemic effects 1
• Alternative: Continuous progestin therapy (megestrol acetate or medroxyprogesterone) 1
• Close monitoring with endometrial sampling every 3-6 months 1

If Hyperplasia With Atypia or Malignancy:

• More aggressive management including surgical options is necessary 1
• Staging investigations must be planned by a multidisciplinary team 1