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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Hence it does not apply to a young woman, who has had amenorrhoea from anorexia nervosa, or a pregnancy followed by lactation. However, it can apply to younger women following premature ovarian insufficiency or premature menopause.
Unscheduled bleeding in women of menopausal age taking hormone replacement therapy (HRT) should be managed in the same way from a practical perspective. 'Unscheduled bleeding' is defined as non-cyclical bleeding still continuing six months after commencing HRT or after six months of amenorrhoea.
Although PMB usually has a benign cause, the priority is to exclude malignancy.
PMB is a common problem representing 5% of all gynaecology outpatient attendances. These are most commonly to eliminate endometrial cancer as the cause of the bleed.
Risk factors for endometrial cancer
- Many risk factors relate to oestrogen exposure.
- Unopposed oestrogen-only HRT.
- Tamoxifen use - it has an anti-oestrogen effect on the breast, but a pro-oestrogen effect on the uterus and bones.
- Low parity or infertility.
- Early menarche and late menopause.
- Increasing age.
- Polycystic ovarian disease.
- Hereditary non-polyposis colorectal carcinoma.
- Obesity combined with diabetes.
Protective factors for endometrial cancer
- Use of combined oral contraceptives decreases risk.
- Grand multiparity.
- Vaginal atrophy. The most common cause of PMB.
- Use of HRT.
- Endometrial hyperplasia; simple, complex, and atypical.
- Endometrial cancer.
- Endometrial polyps or cervical polyps.
- Cervical cancer; remember to check if the cervical smear is up to date.
- Uterine sarcoma (rare).
- Ovarian cancer, especially oestrogen-secreting (theca cell) ovarian tumours.
- Vaginal cancer (very uncommon).
- Vulval cancer may bleed, but the lesion should be obvious.
- Non-gynaecological causes including trauma or a bleeding disorder.
History and examination may possibly indicate cause, but it is generally accepted that PMB should be treated as malignant, until proved otherwise.
This requires referral to a gynaecologist with an appointment within two weeks.
Transvaginal ultrasound scan (TVUS)
TVUS is an appropriate first-line procedure to identify which women with PMB are at higher risk of endometrial cancer.
The mean endometrial thickness in postmenopausal women is much thinner than in pre-menopausal women. Thickening of the endometrium may indicate the presence of pathology. In general, the thicker the endometrium, the higher the likelihood of important pathology, ie endometrial cancer being present.
The threshold in the UK and the USA is 5 mm. There is some uncertainty regarding the optimal cutoff for endometrial thickness. Several meta-analyses that have used a cutoff measurement of 5 mm or less had a 96% sensitivity and a post-test probability of 2.5% for endometrial cancer in postmenopausal women. However, there is a false positive rate of over 70%.
A definitive diagnosis in PMB is made by histology. Historically, endometrial samples have been obtained by dilatation and curettage. Nowadays it is more usual to obtain a sample by endometrial biopsy, which can be undertaken using samplers. It is most often done as an outpatient procedure, in a hospital or community clinic, or sometimes a GP surgery[5, 6].
When an adequate sample is obtained, the Pipelle® method has high diagnostic accuracy, with a positive predictive value of 81.7% and a negative predictive value of 99.1%. However, adequate samples can be difficult to obtain. One study showed that only 34% of patients had an adequate sample. This percentage rose to 60% when evaluating women with an endometrial thickness of at least 5 mm.
NB: every method of sampling the endometrium has the potential to miss some cancers.
Hysteroscopy and biopsy (curettage) are the preferred diagnostic technique to detect polyps and other benign lesions. Hysteroscopy may be performed as an outpatient procedure, although some women will need GA.
Referral to 'one stop' specialised clinics is ideal. At such clinics several investigations are available to complement clinical evaluation, including ultrasound, endometrial sampling techniques and hysteroscopy. Following such assessment, reassurance can be given or further investigations or treatment can be discussed and arranged.
Most women with PMB will not have significant pathology but the dictum remains that postmenopausal bleeding is cancer until proved otherwise.
- PMB in women on HRT still needs investigation.
- An obvious lesion such as atrophic vaginitis does not exclude another lesion.
- Many women are unable to distinguish between vaginal and urinary bleeding and some are unable to distinguish rectal bleeding.
Women with breast cancer who take tamoxifen on a long-term basis are at increased risk of endometrial cancer. In view of the increased risk of endometrial cancer associated with tamoxifen therapy, there is a case for heightened vigilance for PMB by both the women and the clinician(s) responsible for their care. Tamoxifen can cause other changes to the endometrium, and ultrasound may be more difficult to interpret. All women with PMB who are on tamoxifen would normally have hysteroscopy and biopsy in addition to ultrasonography.
Further reading and references
Collins J, Crosignani PG; Endometrial bleeding. Hum Reprod Update. 2007 Sep-Oct13(5):421-31. Epub 2007 Mar 2.
Gynaecological cancers - recognition and referral; NICE CKS, November 2016 (UK access only)
Braun MM, Overbeek-Wager EA, Grumbo RJ; Diagnosis and Management of Endometrial Cancer. Am Fam Physician. 2016 Mar 1593(6):468-74.
Suspected cancer: recognition and referral; NICE Clinical Guideline (2015 - last updated September 2020)
Wong AW, Lao TH, Cheung CW, et al; Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study. BJOG. 2015 Mar 20. doi: 10.1111/1471-0528.13342.
Schramm A, Ebner F, Bauer E, et al; Value of endometrial thickness assessed by transvaginal ultrasound for the prediction of endometrial cancer in patients with postmenopausal bleeding. Arch Gynecol Obstet. 2017 Aug296(2):319-326. doi: 10.1007/s00404-017-4439-0. Epub 2017 Jun 20.
Dickson JM, Delaney B, Connor ME; Primary care endometrial sampling for abnormal uterine bleeding: a pilot study. J Fam Plann Reprod Health Care. 2017 Oct43(4):296-301. doi: 10.1136/jfprhc-2017-101735. Epub 2017 Aug 19.
Narice BF, Delaney B, Dickson JM; Endometrial sampling in low-risk patients with abnormal uterine bleeding: a systematic review and meta-synthesis. BMC Fam Pract. 2018 Jul 3019(1):135. doi: 10.1186/s12875-018-0817-3.
Centini G, Troia L, Lazzeri L, et al; Modern operative hysteroscopy. Minerva Ginecol. 2016 Apr68(2):126-32. Epub 2016 Mar 1.
Lotfallah H, Farag K, Hassan I, et al; One-stop hysteroscopy clinic for postmenopausal bleeding. J Reprod Med. 2005 Feb50(2):101-7.