Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Endometrial cancer and postmenopausal bleeding
Obstetrics and gynaecology · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Stabilise heavy bleeding and severe anaemia first
Most postmenopausal bleeding is not an immediate emergency, but ongoing heavy loss, haemodynamic disturbance, syncope, chest pain, severe breathlessness or sepsis requires acute care before outpatient cancer investigation.
Action: Record observations, establish intravenous access and blood count and group-and-save when indicated, resuscitate and control bleeding with senior gynaecology input, while preserving an urgent pathway to tissue diagnosis.
Overview
Treat postmenopausal bleeding as a cancer signal, use ultrasound and tissue sampling without false reassurance, and connect histology, molecular testing and stage to treatment.
Postmenopausal bleeding is a presentation, not a diagnosis. Confirm that menstruation stopped because of menopause more than 12 months earlier and characterise onset, recurrence, amount, pain and discharge. Ask about HRT regimen and timing, tamoxifen, anticoagulants, cervical screening, previous hyperplasia, obesity, diabetes and family history. Clarify whether apparent vaginal blood could be haematuria or rectal bleeding, because a negative endometrial test does not investigate those sources.
NICE NG12 changed its wording in April 2026 to account for HRT. A person aged 55 or over with unexplained postmenopausal bleeding that cannot be attributed to HRT should be referred on the suspected-cancer pathway; under 55, the same referral should be considered. Unexplained means the bleeding is outside expected HRT timing and has no established benign cause after initial assessment. It is unsafe to apply the HRT caveat without documenting the preparation, start or change date and bleeding pattern.
Practice
Two practice questions
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Question 1 of 2
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Obstetrics and gynaecologyOriginal SBA
Referring unexplained bleeding
A 58-year-old who is not taking HRT reports vaginal bleeding eighteen months after her last natural menstrual period. She is stable and examination shows no obvious lower-genital-tract cause. What should happen next?
Sources and review status6 sources · checked 27 Aug 2026 · clinical review pending+
Sources
Sources and review status
National guidance is shown before implementation-dependent detail. Apply principles in context and verify current guidance when a decision affects care. Source check completed 27 Aug 2026; clinical approval remains outstanding.
NICE NG23 recognises that unscheduled bleeding is common in the first 6 months after starting systemic HRT and within 3 months of changing the dose or preparation. Beyond those periods, advise prompt medical review. Even within them, heavy or prolonged bleeding, anaemia, risk factors or an examination abnormality can justify earlier investigation. NICE notes limited direct evidence and signposts the British Menopause Society joint guidance, so decisions should be risk assessed rather than reduced to one date threshold.
Examination can reveal atrophic trauma, a urethral lesion, vulval disease, a vaginal or cervical tumour, infection or a uterine mass. Offer a chaperone, explain speculum and bimanual examination and stop if requested. Atrophy is common but should be a positive clinical explanation, not an assumption made without inspection. A malignant-looking cervix or vulval lesion follows its own urgent referral route, while uterine investigation continues when the source remains uncertain.
Transvaginal ultrasound is the usual initial uterine test in a rapid-access clinic. Measure the double-layer endometrial thickness in the sagittal plane and describe uniformity, focal lesions, intracavitary fluid, myometrium and adnexa. In a first spontaneous bleeding episode without systemic HRT, a fully seen, regular endometrium of 4 mm or less has a very low probability of endometrial cancer and can support discharge with explicit return advice. For unscheduled bleeding on HRT, current BMS guidance uses 4 mm or less with continuous-combined HRT and 7 mm or less with sequential HRT when the endometrium is uniform and fully visualised. Poor visualisation is not a thin measurement, and recurrent bleeding overrides a previous scan.
Thickness above the applicable threshold, meaning above 4 mm without systemic HRT or with continuous-combined HRT and above 7 mm with sequential HRT, requires urgent endometrial assessment. Focal or irregular change, inability to measure or continuing bleeding also needs tissue assessment regardless of the number. An outpatient Pipelle samples diffuse disease but can miss focal lesions and may be insufficient in an atrophic cavity. Hysteroscopy visualises the cavity and directs biopsy of a polyp or suspicious area. An insufficient blind sample should be interpreted with thickness, insertion, symptoms and risk; it must not close the case when the scan is abnormal or bleeding persists.
Endometrial carcinoma includes endometrioid, serous, clear-cell, carcinosarcoma and other histologies with different biology. Histology establishes grade and subtype, while MRI helps assess myometrial and cervical stromal invasion before treatment. CT evaluates extrauterine disease in higher-risk cancer. Surgical staging usually uses minimally invasive total hysterectomy and bilateral salpingo-oophorectomy, with sentinel-node mapping or lymph-node assessment selected from histology, grade, invasion, imaging and molecular risk.
Adjuvant treatment is not determined by stage alone. The MDT integrates myometrial invasion, lymphovascular space invasion, nodes, histological subtype and molecular class. Low-risk disease may need surgery alone; increasing pelvic or systemic relapse risk may lead to vaginal brachytherapy, external-beam radiotherapy, chemotherapy or combinations. Advanced or recurrent disease can use surgery, systemic therapy, endocrine therapy or radiation according to distribution, tumour markers, fitness and goals.
Universal Lynch triage is part of diagnosis. NICE HTG557 recommends mismatch-repair immunohistochemistry for all endometrial cancers. Loss of MLH1 alone or MLH1 with PMS2 leads to tumour MLH1 promoter hypermethylation testing; absent methylation then leads to germline testing. Loss of MSH2, MSH6 or isolated PMS2 leads directly to germline testing. Explain that a tumour result can affect treatment and may reveal inherited risk for the patient and relatives.
Fertility-sparing management is exceptional. A person wishing to retain fertility may be considered only after expert pathology confirms carefully selected grade 1 endometrioid carcinoma confined to the endometrium and imaging excludes myometrial invasion or extrauterine cancer. Treatment uses specialist progestogen-based protocols with repeated endometrial sampling and a defined endpoint; non-response, progression or completion of childbearing leads to definitive surgery. It is not suitable for higher-grade, non-endometrioid or invasive disease.
Key points
Postmenopausal bleeding means vaginal bleeding more than 12 months after menstruation stopped because of menopause; identify whether the blood is vaginal, urinary or rectal.
Under NICE NG12 updated April 2026, refer age 55 or over on the suspected-cancer pathway for unexplained postmenopausal bleeding not attributable to HRT; consider that pathway under 55.
Bleeding is common during the first 6 months after starting systemic HRT or within 3 months of changing dose or preparation, but heavy, prolonged or later bleeding still needs assessment using current BMS-linked guidance.
Perform consented vulval, speculum and pelvic assessment according to presentation because atrophy, cervical disease, trauma and visible lesions may be the source.
Transvaginal ultrasound measures endometrial thickness and identifies focal or adnexal pathology. In an initial episode, a fully visualised uniform endometrium of 4 mm or less is reassuring without systemic HRT or with continuous-combined HRT; current BMS guidance uses 7 mm or less for sequential HRT.
Endometrium above the applicable threshold, focal abnormality, poor visualisation or persistent or recurrent bleeding leads to urgent endometrial assessment by biopsy and often hysteroscopy-directed sampling.
Definitive endometrial cancer diagnosis is histological. Standard surgical staging commonly uses total hysterectomy and bilateral salpingo-oophorectomy with nodal assessment selected by risk and specialist protocol.
Aetiology
01
Unopposed oestrogenic stimulation
Adipose aromatisation, chronic anovulation or exogenous oestrogen without adequate progestogen can drive endometrial proliferation, atypical hyperplasia and endometrioid carcinoma over time.
02
Mismatch-repair predisposition
Pathogenic MLH1, MSH2, MSH6 or PMS2 variants cause Lynch syndrome, impair DNA repair and increase endometrial as well as colorectal and other cancer risks.
03
Non-endometrioid pathways
Serous, clear-cell, carcinosarcoma and other high-risk tumours arise through distinct molecular routes and may occur without the classic obesity or prolonged-oestrogen phenotype.
Pathophysiology
1
Precursor progression
Accumulating molecular alterations transform proliferative endometrium through atypical hyperplasia or endometrial intraepithelial neoplasia into invasive endometrioid carcinoma in many cases.
2
Myometrial invasion
Tumour penetrates the myometrium and may enter lymphovascular channels, increasing pelvic nodal and distant relapse risk beyond a cavity-confined lesion.
3
Molecular divergence
Mismatch-repair deficiency, POLE mutation, abnormal p53 and non-specific molecular profiles define biologically different groups that increasingly refine prognosis and adjuvant decisions.
4
Extrauterine dissemination
Cancer can extend to cervix, serosa and adnexa or spread through lymphatic, peritoneal and haematogenous routes to nodes, peritoneum, lung, liver and bone.
Clinical features and red flags
Unexplained postmenopausal bleeding
Bleeding after twelve months of amenorrhoea from menopause is unexplained when HRT timing or a confirmed benign source does not account for it and therefore needs cancer-focused assessment.
HRT settling pattern
Unscheduled bleeding can occur within six months of starting systemic HRT or three months after a regimen change, but severity, persistence and individual risk determine whether investigation can wait.
Thin but recurrent bleeding
A properly visualised endometrium within the regimen-appropriate threshold is reassuring for one episode, while recurrence requires renewed assessment because focal or uncommon cancer can be missed.
Endometrial risk context
Obesity, chronic anovulation, unopposed oestrogen, diabetes, tamoxifen, prior hyperplasia and Lynch syndrome increase concern but their absence never makes postmenopausal bleeding normal.
Advanced disease pattern
Pelvic mass, persistent pain, weight loss, ascites, nodal enlargement or urinary and bowel symptoms suggest extrauterine disease and broaden staging beyond the uterine cavity.
Red flags requiring action
Unexplained bleeding more than 12 months after natural menopause in someone aged 55 or over requires a suspected-cancer pathway referral when it cannot be attributed to HRT.
Postmenopausal bleeding under age 55 still warrants consideration of the suspected-cancer pathway and should not be dismissed because age lowers absolute risk.
Investigations
01Transvaginal ultrasoundFirst step
Why
Measure and characterise the endometrium and assess the uterus and adnexa after postmenopausal bleeding.
Interpretation and limitations
A fully visualised uniform endometrium is reassuring after an initial episode at 4 mm or less without systemic HRT or with continuous-combined HRT, and at 7 mm or less with sequential HRT; focal change, poor visualisation or recurrent bleeding still requires assessment.
02Outpatient endometrial biopsy
Why
Sample the endometrium for hyperplasia or carcinoma when ultrasound or clinical persistence indicates tissue diagnosis.
Interpretation and limitations
Adequate benign tissue can be reassuring in the right context, but insufficient tissue or a benign blind sample does not reliably exclude a focal lesion or resolve continuing bleeding.
03Hysteroscopy with directed biopsy
Why
Inspect the cavity and target a polyp, irregular area or lesion missed by blind sampling.
Interpretation and limitations
Directed histology distinguishes benign focal disease, atypical hyperplasia and malignancy; procedural tolerance and pain-control options should be agreed before starting.
04Pelvic MRI and staging CT
Why
Estimate local invasion and distant distribution after cancer is histologically confirmed.
Interpretation and limitations
MRI contributes myometrial and cervical stromal assessment, while CT addresses nodal or extra-pelvic disease; imaging refines but does not replace surgical and pathological staging.
Differential diagnosis
01
Genitourinary atrophy
Thin fragile vulvovaginal epithelium commonly causes light bleeding, but the diagnosis requires compatible examination and does not cancel endometrial assessment when bleeding remains unexplained.
02
Endometrial polyp or hyperplasia
Focal polyps and diffuse hyperplasia can bleed after menopause; hysteroscopy and histology distinguish benign tissue from atypia or carcinoma.
03
Cervical or vaginal disease
Cervicitis, polyps, trauma and lower-genital malignancy can mimic uterine bleeding and are sought by careful speculum inspection rather than ultrasound alone.
04
Urinary or rectal bleeding
Haematuria and rectal bleeding are sometimes reported as vaginal; targeted examination and testing prevent a negative uterine pathway from delaying another cancer diagnosis.
05
HRT-related bleeding
Sequential withdrawal bleeding or early unscheduled bleeding after starting or changing systemic HRT may be expected, but timing, persistence and risk factors determine investigation.
Management
01Initial bleedingConfirm source and urgencyFirst stepBleeding occurs more than twelve months after menstruation stopped because of menopause.+
1Assess amount, recurrence, pain, haemodynamic symptoms and whether blood is vaginal, urinary or rectal, then document HRT type and the timing of any start or change.
2Use the suspected-cancer pathway for unexplained postmenopausal bleeding at 55 or over and consider it under 55, while applying acute care to major blood loss.
3Inspect the vulva, vagina and cervix with consent and arrange rapid uterine assessment unless another source has been confidently established and managed.
02Uterine diagnosisCombine thickness with persistenceThe person reaches a postmenopausal bleeding assessment service or symptoms continue after initial review.+
1Obtain transvaginal ultrasound with a documented, fully visualised endometrial measurement and description of focal, myometrial and adnexal findings.
Complications
01
Anaemia and haemorrhage
Repeated or heavy uterine bleeding can cause iron deficiency, symptomatic anaemia and occasionally haemodynamic compromise before definitive cancer treatment.
02
Pelvic organ invasion
Progressive tumour may reach cervix, adnexa, bladder or bowel, producing pain, urinary and gastrointestinal dysfunction, bleeding and fistula.
03
Nodal or distant metastasis
Lymphovascular spread can involve pelvic and para-aortic nodes, while advanced disease may seed peritoneum, lung, liver, bone or other organs.
04
Treatment-related menopause
Bilateral oophorectomy, radiotherapy and systemic treatment can produce abrupt vasomotor, genitourinary, bone, cardiovascular and sexual consequences requiring active support.
05
Hereditary cancer burden
Unrecognised Lynch syndrome leaves the patient and relatives without indicated colorectal surveillance, risk-reducing options and cascade testing opportunities.
Monitoring and follow-up
A person discharged after a thin endometrium needs explicit advice to return for any recurrent bleeding, because the reassurance applies to that assessment rather than all future episodes.
Track every endometrial sample to an adequate histological result and reconcile insufficient tissue with ultrasound, ongoing symptoms and cancer risk.
After treatment, monitor bleeding, discharge, pelvic or abdominal pain, urinary and bowel change and weight loss alongside late surgical or radiotherapy effects.
Ensure mismatch-repair, MLH1 methylation and germline outcomes are communicated, with genetics referral and cascade-testing support when Lynch syndrome is confirmed.
For fertility-sparing treatment, use the specialist biopsy schedule and stop conservative management for non-response, progression, unreliable surveillance or completion of reproductive plans.
Special situations
HRT attribution needs dates
Calling bleeding HRT related is defensible only after documenting regimen, expected bleed pattern and time since starting or changing treatment, not merely recording HRT use.
Poorly seen is not thin
An endometrium that cannot be measured confidently because of fibroids, position, fluid or technical limitation must not be reported clinically as reassuringly thin.
Persistence outranks one test
Repeated bleeding can reveal a focal lesion missed by a blind sample or a rare tumour that presents despite a previously small thickness.
Tumour testing opens family care
Mismatch-repair loss can lead from one endometrial cancer diagnosis to germline confirmation, colorectal prevention and cascade testing for relatives.
Fertility preservation is conditional
Progestogen-based conservative care treats selected disease temporarily and requires repeated tissue proof; it is neither surveillance alone nor a permanent substitute for definitive surgery.
Common pitfalls
01
Dismissing postmenopausal bleeding as atrophy or anticoagulant related without confirming the source and completing cancer assessment.
02
Treating every bleed during HRT as expected without checking whether it lies beyond six months from starting or three months from changing treatment.
03
Equating an unmeasurable endometrium or insufficient Pipelle specimen with a negative cancer investigation.
04
Discharging recurrent bleeding solely because an earlier ultrasound measured the lining at four millimetres or less.
05
Using hysteroscopy findings without histology to declare a suspicious lesion benign.
06
Limiting Lynch testing to young patients or striking family histories despite the universal endometrial-cancer recommendation.
Offer Lynch syndrome testing to every person diagnosed with endometrial cancer using mismatch-repair immunohistochemistry, followed by MLH1 methylation or germline testing according to the loss pattern.
Persistent or recurrent bleeding needs further assessment even after a thin endometrium, benign blind biopsy or initially reassuring examination.
A visible cervical, vaginal or vulval lesion, pelvic mass, ascites or enlarged nodes redirects urgent assessment toward the anatomical abnormality as well as the endometrium.
Tachycardia, hypotension, syncope, rapidly falling haemoglobin or ongoing profuse loss requires same-day emergency management.
05Mismatch-repair immunohistochemistry
Why
Screen every endometrial cancer for a tumour pattern suggesting Lynch syndrome and provide molecular information.
Interpretation and limitations
MLH1 or paired MLH1-PMS2 loss requires MLH1 promoter methylation testing; unmethylated loss, MSH2 or MSH6 loss, or isolated PMS2 loss leads to germline assessment.
2Use urgent biopsy and hysteroscopy for thickness above 4 mm without systemic HRT or with continuous-combined HRT, above 7 mm with sequential HRT, or for focal or irregular findings, poor visualisation, significant risk or recurrent bleeding.
3EscalationReconcile histology, imaging and symptoms; repeat or escalate discordant assessment, and send confirmed cancer to the gynaecological oncology MDT.
03Cancer managementIntegrate pathological and molecular riskEndometrial biopsy confirms carcinoma or a premalignant lesion requiring specialist care.+
1Stage with appropriate imaging, review fertility wishes before treatment and plan hysterectomy, salpingo-oophorectomy and nodal assessment according to specialist risk stratification.
2Use final stage, histology, grade, invasion, lymphovascular space, nodes and molecular class to select observation, brachytherapy, external-beam radiotherapy, systemic treatment or a combination.
3Complete mismatch-repair and Lynch testing, provide results and family implications, and establish follow-up that addresses recurrence symptoms, menopause, sexual health and treatment toxicity.