Postmenopausal bleeding (PMB) is defined for practical purposes as vaginal bleeding occurring after twelve months of amenorrhoea, in a woman of the age where the menopause can be expected.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 failure 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.
Postmenopausal bleeding 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.
- 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.
- Cigarette smoking.
- Vaginal atrophy. The most common cause of PMB.
- Use of HRT.
- Endometrial hyperplasia; simple, complex, and atypical.
- Endometrial cancer. The probability of a woman presenting with PMB having endometrial cancer is 10%. However, 90% of women with endometrial cancer present with PMB.
- 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 premenopausal 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 is 5 mm; a thickness of >5 mm gives 7.3% likelihood of endometrial cancer.In a woman with PMB, if endometrial thickness is less than 5 mm uniformly, the probability of carcinoma is less than 1%.Some pathology may be missed and it is recommended that hysteroscopy and biopsy should be performed if clinical suspicion is high.The accuracy of assessing endometrial thickness in women with diabetes and obesity has been questioned.However, models have been developed to take personal characteristics into account when predicting the risk of cancer.
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. Endometrial biopsy can be performed as either an outpatient procedure, or under general anaesthetic (GA). All methods of sampling the endometrium will 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 require GA. Where they are available, 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.
Where pathology is found it needs to be treated and prognosis will depend upon the condition and, if malignant, the stage. One stop clinics provide a fast and efficient way of investigating PMB.
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 like 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. One paper found that, in women presenting with PMB, the prevalence of bladder tumours was 1.07% and of bladder cancer was 0.7%.
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 on tamoxifen would normally have hysteroscopy and biopsy in addition to ultrasonography.
Further reading and references
Gynaecological cancer - suspected; NICE CKS, July 2005 (UK access only)
Collins J, Crosignani PG; Endometrial bleeding. Hum Reprod Update. 2007 Sep-Oct13(5):421-31. Epub 2007 Mar 2.
Investigation of post-menopausal bleeding; Scottish Intercollegiate Guidelines Network - SIGN (2002)
Moodley M, Roberts C; Clinical pathway for the evaluation of postmenopausal bleeding with an emphasis on endometrial cancer detection. J Obstet Gynaecol. 2004 Oct24(7):736-41.
Saso S, Chatterjee J, Georgiou E, et al; Endometrial cancer. BMJ. 2011 Jul 6343:d3954. doi: 10.1136/bmj.d3954.
Sahdev A; Imaging the endometrium in postmenopausal bleeding. BMJ. 2007 Mar 24334(7594):635-6.
Referral for suspected cancer; NICE Clinical Guideline (2005)
Smith-Bindman R, Weiss E, Feldstein V; How thick is too thick? When endometrial thickness should prompt biopsy in postmenopausal women without vaginal bleeding. Ultrasound Obstet Gynecol. 2004 Oct24(5):558-65.
Litta P, Merlin F, Saccardi C, et al; Role of hysteroscopy with endometrial biopsy to rule out endometrial cancer in postmenopausal women with abnormal uterine bleeding. Maturitas. 2005 Feb 1450(2):117-23.
van Doorn LC, Dijkhuizen FP, Kruitwagen RF, et al; Accuracy of transvaginal ultrasonography in diabetic or obese women with postmenopausal bleeding. Obstet Gynecol. 2004 Sep104(3):571-8.
Opmeer BC, van Doorn HC, Heintz AP, et al; Improving the existing diagnostic strategy by accounting for characteristics of the women in the diagnostic work up for postmenopausal bleeding. BJOG. 2007 Jan114(1):51-8.
Lotfallah H, Farag K, Hassan I, et al; One-stop hysteroscopy clinic for postmenopausal bleeding. J Reprod Med. 2005 Feb50(2):101-7.
Abdel-Fattah M, Barrington JW, Youssef M, et al; Prevalence of bladder tumors in women referred with postmenopausal bleeding. Gynecol Oncol. 2004 Jul94(1):167-9.
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