What are the guidelines for managing postmenopausal bleeding in women on Hormone Replacement Therapy (HRT) under the two-week rule?

Management of Postmenopausal Bleeding in Women on HRT Under the Two-Week Rule

Women with postmenopausal bleeding on HRT should be urgently referred under the two-week rule for investigation, with transvaginal ultrasound as the initial investigation, followed by endometrial sampling or hysteroscopy if endometrial thickness exceeds 4mm.

Initial Assessment and Referral

Postmenopausal bleeding (PMB) in women on HRT is a common issue but requires prompt investigation due to the risk of endometrial cancer. The management follows these key steps:

1. Urgent referral under the two-week rule for all women with PMB on HRT
2. Initial investigation with transvaginal ultrasound (TVUS) to measure endometrial thickness
3. Further investigation pathway determined by endometrial thickness findings

Diagnostic Algorithm

Step 1: Transvaginal Ultrasound Assessment

• Perform TVUS at the end of the progestational sequence in women on sequential HRT 1
• Measure endometrial thickness

Step 2: Follow Investigation Pathway Based on TVUS Findings

• If endometrial thickness ≤4mm:

  • Single episode of bleeding: Can postpone further uterine exploration 1, 2
  • Continue monitoring

• If endometrial thickness >4mm OR recurrent bleeding:

  • Proceed with additional uterine investigations:
    • Hysteroscopy
    • Endometrial sampling for histology 1, 2

Risk Assessment

Women on combined HRT have a significantly lower risk of endometrial cancer compared to non-HRT users when presenting with PMB (adjusted odds ratio = 0.229,95% CI 0.116-0.452) 3. However, investigation remains essential as:

• Breakthrough bleeding is a common problem in women on HRT 4
• Unscheduled bleeding is often the presenting symptom of endometrial adenocarcinoma 4
• The risk of diagnosing endometrial cancer may increase with longer duration of HRT use 3

Important Considerations

• Breakthrough bleeding is one of the main factors for poor adherence to HRT 1
• PMB must always be evaluated to rule out endometrial cancer 4
• Combined HRT regimens tend to be predominantly progestogenic, which may cause vascular changes similar to those seen with progestogen-only contraceptives 4

Causes of Abnormal Uterine Bleeding on HRT

Organic Causes

• Endometrial cancer (primary concern)
• Endometrial polyps
• Submucosal fibroids
• Endometrial hyperplasia

Functional Causes

• Resumption of ovarian activity
• Poor compliance with HRT regimen
• Trophic disorders of the endometrium 1

Pitfalls and Caveats

• Do not assume bleeding is simply due to HRT use without proper investigation
• Regular bleeding patterns do not absolutely rule out abnormal histopathology 5
• Transvaginal sonography alone is not sufficient to screen asymptomatic women on HRT for endometrial abnormalities 5
• Women on continuous combined HRT or tibolone may experience spotting or bleeding at the beginning of treatment, but persistent bleeding requires investigation 5

By following this evidence-based approach to investigating PMB in women on HRT, clinicians can ensure timely diagnosis of potential endometrial cancer while avoiding unnecessary procedures in low-risk cases.