What is the treatment for a 55-year-old postmenopausal female on Hormone Replacement Therapy (HRT) by monthly injection who develops vaginal bleeding?

Management of Vaginal Bleeding in a Postmenopausal Woman on Monthly HRT Injections

Stop the HRT immediately and perform urgent endometrial evaluation with transvaginal ultrasound and/or endometrial biopsy to rule out endometrial cancer, as postmenopausal bleeding on HRT requires investigation for malignancy before any other intervention. 1, 2

Immediate Diagnostic Workup

Rule out pregnancy, infection, and structural pathology first before attributing bleeding to HRT side effects. 3 This includes:

• Transvaginal ultrasound at the end of any progestational sequence to measure endometrial thickness 2
• If endometrial thickness ≤4mm and single bleeding episode: Consider postponing further exploration 2
• If endometrial thickness >4mm or recurrent bleeding: Proceed immediately to hysteroscopy with histological sampling 2
• Endometrial biopsy is mandatory for any postmenopausal woman with abnormal bleeding, as endometrial cancer is the most serious etiology requiring exclusion 1, 4

Reassess HRT Indication and Formulation

Discontinue HRT unless there are compelling reasons to continue, particularly if bleeding occurred while on therapy. 1 The key considerations include:

• Monthly injections are not standard HRT formulation - the evidence base supports transdermal or oral 17β-estradiol with appropriate progestogen protection 1
• Assess whether adequate progestogen protection exists - unopposed estrogen dramatically increases endometrial cancer risk 5
• If HRT must continue after malignancy is excluded, switch to evidence-based regimens with proper endometrial protection 1

Treatment Algorithm Based on Findings

If Benign Pathology Identified (polyps, fibroids, adenomyosis):

• Hysteroscopic resection-ablation effectively treats refractory bleeding from benign uterine pathology in 85.7% of cases 6
• Consider switching to continuous combined HRT (estrogen plus daily progestogen) rather than sequential regimens to reduce bleeding episodes 5, 7

If No Structural Pathology and Bleeding Persists:

• First-line: NSAIDs for 5-7 days during bleeding episodes (celecoxib 200mg daily or mefenamic acid 500mg TID) 3
• Second-line: Increase progestogen dose - doubling the progestin component stops bleeding in 87% of women with breakthrough bleeding on continuous HRT 6
• Third-line: Short-term hormonal treatment with low-dose combined oral contraceptives or estrogen for 10-20 days 3

Optimal HRT Regimen if Continuation Warranted

Switch from monthly injections to transdermal 17β-estradiol (50-100μg patches) with cyclical oral micronized progesterone (200mg for 12-14 days every 28 days) or continuous combined formulations. 1 This approach provides:

• Better endometrial protection with micronized progesterone as first-choice progestogen (lower cardiovascular and thrombotic risk) 1
• Continuous combined regimens (estrogen + progestogen daily without interruption) avoid withdrawal bleeding and improve compliance 1
• Transdermal delivery minimizes thrombotic factor activation compared to oral or injectable routes 1

Critical Caveats

Never attribute postmenopausal bleeding to "normal HRT side effects" without excluding malignancy - endometrial cancer presents with bleeding and must be ruled out in every case. 1, 2

Monthly injectable HRT is not a standard evidence-based regimen - the literature supports transdermal or oral estradiol with appropriate progestogen cycling, not injectable formulations. 1

If bleeding recurs after initial evaluation and treatment, repeat endometrial assessment - persistent abnormal uterine bleeding warrants re-evaluation for underlying gynecological problems. 3, 2

Use the lowest effective HRT dose for the shortest duration when therapy is indicated for severe vasomotor symptoms that cannot be managed with non-hormonal treatments. 1, 4