Definition

Postmenopausal bleeding (PMB) is 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.

Epidemiology

It is a common problem representing 5% of all gynaecology outpatient attendances.¹ These are to eliminate endometrial cancer as the cause of the bleed.

Risk factors for endometrial cancer²

• It is likely to occur if exogenous oestrogens are taken.
• Tamoxifen has an anti-oestrogen effect on the breast, but a pro-oestrogen effect on the uterus and bones.
• Polycystic ovarian disease increases risk.
• Hereditary non-polyposis colorectal carcinoma.
• Obesity combined with diabetes.
• Use of combined oral contraceptives decreases risk.

Aetiology

• Non-gynaecological causes including trauma or a bleeding disorder.
• Use of hormone replacement therapy (HRT).
• Vaginal atrophy.
• Endometrial hyperplasia; simple, complex, and atypical.
• Endometrial carcinoma usually presents as PMB, but 25% occur in premenopausal women.
• Endometrial polyps or cervical polyps.
• Carcinoma of cervix; remember to check if the cervical smear is up-to-date.
• Uterine sarcoma (rare).
• Ovarian carcinoma, especially oestrogen-secreting (theca cell) ovarian tumours.
• Vaginal carcinoma is very uncommon.
• Carcinoma of vulva may bleed, but the lesion should be obvious.

Management

History and examination may possibly indicate cause, but it is generally accepted that postmenopausal bleeding should be treated as malignant, until proved otherwise.
This requires referral to a gynaecologist with an appointment within two weeks.³

Investigations

Transvaginal Ultrasound Scan

Where sufficient local skills and resources exist, transvaginal ultrasound scan (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, i.e. endometrial cancer being present. The threshold in the UK is 5 mm; a thickness of >5 mm gives 7.3% likelihood of endometrial cancer.⁴ A thickness of <5 mm has a negative predictive value of 98%.²
A recent meta-analysis found that a TVUS result of 5 mm or less reduced the risk of disease by 84%.⁵ Some pathology may be missed and it is recommended that hysteroscopy and biopsy should be performed if clinical suspicion is high.^6,7 The accuracy of assessing endometrial thickness in women with diabetes and obesity has been questioned,⁸ but models have been developed to take personal characteristics into account when predicting the risk of cancer.⁹

Endometrial biopsy

A definitive diagnosis in postmenopausal bleeding 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

Hysteroscopy and biopsy (curettage) is 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.
A significant development has been direct referral to 'one stop' specialist clinics.^10,11 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.

Outcome

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.

Cautions

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%.¹²

Tamoxifen

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 postmenopausal bleeding by both the women and the clinician(s) responsible for their care.
Ultrasonography is poor at differentiating potential cancers from other tamoxifen-induced thickening because of the distorted endometrial architecture associated with long-term use of tamoxifen.¹³ Ultrasonographic evaluation could have a higher cut-off point of endometrial thickness, e.g. 9 mm, as a prompt for further investigation. Hysteroscopy with biopsy is preferable as the first line of investigation in women taking tamoxifen who experience postmenopausal bleeding.

Document references

1. Moodley M, Roberts C; Clinical pathway for the evaluation of postmenopausal bleeding with an emphasis on endometrial cancer detection. J Obstet Gynaecol. 2004 Oct;24(7):736-41. [abstract]
2. Sahdev A; Imaging the endometrium in postmenopausal bleeding. BMJ. 2007 Mar 24;334(7594):635-6.
3. Referral for suspected cancer, NICE Clinical Guideline (2005)
4. 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 Oct;24(5):558-65. [abstract]
5. Gupta JK, Chien PF, Voit D, et al; Ultrasonographic endometrial thickness for diagnosing endometrial pathology in women with postmenopausal bleeding: a meta-analysis. Acta Obstet Gynecol Scand. 2002 Sep;81(9):799-816. [abstract]
6. Garuti G, Sambruni I, Cellani F, et al; Hysteroscopy and transvaginal ultrasonography in postmenopausal women with uterine bleeding. Int J Gynaecol Obstet. 1999 Apr;65(1):25-33. [abstract]
7. 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 14;50(2):117-23. [abstract]
8. van Doorn LC, Dijkhuizen FP, Kruitwagen RF, et al; Accuracy of transvaginal ultrasonography in diabetic or obese women with postmenopausal bleeding. Obstet Gynecol. 2004 Sep;104(3):571-8. [abstract]
9. 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 Jan;114(1):51-8. [abstract]
10. Panda JK; One-stop clinic for postmenopausal bleeding. J Reprod Med. 2002 Sep;47(9):761-6. [abstract]
11. Lotfallah H, Farag K, Hassan I, et al; One-stop hysteroscopy clinic for postmenopausal bleeding. J Reprod Med. 2005 Feb;50(2):101-7. [abstract]
12. Abdel-Fattah M, Barrington JW, Youssef M, et al; Prevalence of bladder tumors in women referred with postmenopausal bleeding. Gynecol Oncol. 2004 Jul;94(1):167-9. [abstract]
13. Franchi M, Ghezzi F, Donadello N, et al; Endometrial thickness in tamoxifen-treated patients: an independent predictor of endometrial disease. Obstet Gynecol. 1999 Jun;93(6):1004-8. [abstract]

Internet and further reading

• Investigation of PMB, SIGN (2002)
• The British Menopause Society
• Gynaecological cancer - suspected, Clinical Knowledge Summaries (2005)

Acknowledgements