Post Menopausal Bleeding

Postmenopausal bleeding (PMB) is defined as:

It is a common problem, representing 5% of all gynaecology outpatient attendances.¹

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 ovary disease increases risk.
• Hereditary non-polyposis colorectal carcinoma
• Obesity combined with diabetes
• Use of combined oral contraceptives decreases risk.

• Non-gynaecological causes including trauma or a bleeding disorder.
• Use of hormone replacement therapy
• 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; this is 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.

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 2 weeks.³

Transvaginal Ultrasound Scan (TVUS)

Where sufficient local skills and resources exist, transvaginal ultrasound is an appropriate first-line procedure to identify which women with post-menopausal bleeding are at higher risk of endometrial cancer.
The mean endometrial thickness in post-menopausal 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 i.e. endometrial cancer being present. The threshold in the UK is 5mm; a thickness of >5mm gives 7.3% likelihood of endometrial cancer.⁴ A thickness of <5mm has a negative predictive value of 98%.²A 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 post-menopausal 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 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 general anesthetic.

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.

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%.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 post-menopausal 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 post-menopausal bleeding.