Postmenopausal bleeding — structured SAQ (15 marks)

(a) Definition and cancer risk (3 marks)

• Definition (1 mark): postmenopausal bleeding is any vaginal bleeding 12 months or more after the last menstrual period.
• Pooled cancer risk (1 mark): about 9% (95% CI 8-11%), with about 91% of endometrial cancers presenting with PMB.
• Source (1 mark): the Clarke 2018 systematic review and meta-analysis in JAMA Internal Medicine (129 studies, 40,790 women).^[1]

(b) One-stop pathway and the threshold (5 marks)

• Pathway (2 marks): focused history and examination (exclude a cervical / vulval / urinary / rectal source), transvaginal ultrasound to measure the double-layer endometrial thickness and look for a focal lesion, then endometrial sampling when thickened or when a focal lesion is seen.
• Karlsson threshold (2 marks): at an endometrial thickness of 4 mm or less the residual risk of any endometrial abnormality was about 5.5%, and no malignant endometrium was thinner than 5 mm (mean cancer thickness 21.1 mm).^[2]
• Smith-Bindman corroboration (1 mark): using a 5 mm threshold, 96% (95% CI 94-98%) of cancers had an abnormal scan — high sensitivity, but a thin endometrium does not close the case if bleeding persists.^[3]

(c) Sampling tools and the safety-net (3 marks)

• Pipelle for diffuse thickening with no focal lesion (but it can miss a focal lesion — its accuracy is quantified in the Dijkhuizen meta-analysis).^[5]
• Saline contrast sonohysterography when a focal intracavitary lesion is suspected; hysteroscopy with directed biopsy for a focal lesion, a failed or non-diagnostic Pipelle, or persistent bleeding despite a thin endometrium.
• Safety-net (1 mark): a single normal thin endometrium plus a negative biopsy is reassuring but not absolute — recurrent or persistent PMB is re-investigated.

(d) GTG 67 hyperplasia and tamoxifen (4 marks)

• RCOG Green-top 67 split (2 marks): non-atypical hyperplasia — first-line LNG-IUS or oral progestin with surveillance biopsy until two consecutive negatives; atypical hyperplasia (EIN) — hysterectomy for a woman not preserving fertility, given the high concurrent-cancer and progression risk (the Henderson 2024 UK audit confirms the shift to first-line medical management of non-atypical disease and stresses tight follow-up of atypical disease in non-hysterectomy patients).^[7]
• Tamoxifen (2 marks): bleeding on tamoxifen is PMB and is investigated as for any PMB — never attributed to the drug without excluding cancer. Tamoxifen-related polyps and subendometrial cysts can artefactually thicken the measured endometrium, skewing the threshold decision; routine screening ultrasound of an asymptomatic woman on tamoxifen is not recommended.^[6]