What are the causes of postmenopausal bleeding (PMB)?

From the Guidelines

Post-menopausal bleeding requires immediate medical evaluation as it may indicate endometrial cancer or other serious conditions, and the first step in the diagnostic pathway should be the measurement of endometrial thickness using transvaginal ultrasound (TVUS) with a cut-off point of 4 mm or 5 mm, followed by endometrial sampling if necessary, as recommended by the most recent study 1. The evaluation typically includes a pelvic examination, TVUS to measure endometrial thickness, and possibly an endometrial biopsy. Common causes include endometrial atrophy (thinning of the uterine lining), polyps, fibroids, hormone therapy, endometrial hyperplasia, or cancer. While most cases (about 90%) are benign, the possibility of endometrial cancer necessitates thorough investigation. Some key points to consider in the evaluation and management of post-menopausal bleeding include:

• The use of TVUS as the first-line screening test for endometrial cancer in postmenopausal women, with an endometrial thickness of 4 mm conveying a negative predictive value for cancer of nearly 100% 1.
• The importance of combining TVUS with transabdominal US to fully assess the pelvic structures and detect both benign endometrial or myometrial pathologies such as endometrial hyperplasia, polyps, adenomyosis, or leiomyomas.
• The need for endometrial tissue sampling in postmenopausal women with a thickened endometrium (≥5 mm) to determine the etiology of endometrial thickening.
• The fact that abnormal echogenicity and texture of the endometrium has been correlated with significant underlying uterine pathology, and that leiomyomas and adenomyosis are other structural causes of abnormal uterine bleeding. Treatment depends on the underlying cause - atrophy may be treated with local estrogen therapy, polyps or fibroids may require surgical removal, and hormone-related bleeding might need adjustment of hormone therapy. Endometrial hyperplasia or cancer would require specific treatments ranging from progestin therapy to hysterectomy. It is essential to note that the risk of endometrial cancer increases with age, obesity, diabetes, hypertension, and certain hormone therapies, making prompt evaluation particularly important for women with these risk factors, as early detection significantly improves outcomes if cancer is present 1.

From the FDA Drug Label

Estrogens increase the chances of getting cancer of the uterus. Report any unusual vaginal bleeding right away while you are taking estrogens. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

• Postmenopausal bleeding is a warning sign that may indicate cancer of the uterus.
• Women taking estrogens should report any unusual vaginal bleeding right away.
• A healthcare provider should check any unusual vaginal bleeding to determine the cause 2.

From the Research

Definition and Prevalence of Postmenopausal Bleeding

• Postmenopausal bleeding is defined as an episode of bleeding 12 months or more after the last menstrual period 3.
• It occurs in up to 10% of women aged over 55 years 3.
• The peak incidence for endometrial carcinoma is between 65 and 75 years of age 3.

Causes of Postmenopausal Bleeding

• Causes of postmenopausal bleeding include:
  • Endometrial carcinoma
  • Cervical carcinoma
  • Vaginal atrophy
  • Endometrial hyperplasia +/- polyp
  • Cervical polyps
  • Hormone-producing ovarian tumours
  • Haematuria and rectal bleeding 3.

Assessment and Investigation

• The aim of assessment and investigation of postmenopausal bleeding is to identify a cause and exclude cancer 3.
• Assessment should start by taking a detailed history, with identification of risk factors for endometrial cancer, as well as a medication history covering use of HRT, tamoxifen and anticoagulants 3.
• Abdominal and pelvic examinations should be carried out to look for masses 3.
• Speculum examination should be performed to see if a source of bleeding can be identified, assess atrophic changes in the vagina and look for evidence of cervical malignancy or polyps 3.
• Ultrasound scan and endometrial biopsy are complementary 3.
• The measurement of endometrial thickness aims to identify which women with postmenopausal bleeding are at significant risk of endometrial cancer 3, 4, 5, 6.

Diagnostic Thresholds

• If the examination is normal, the bleeding has stopped and the endometrial thickness is < 5 mm on transvaginal ultrasound scan, no further action need be taken 3.
• A threshold of 4 mm can be used to maximize sensitivity, with a sensitivity of 90.6% 6.
• Decreasing the threshold to 3 mm can increase sensitivity to 96.9%, but may compromise test accuracy, specificity, and positive predictive values 6.
• There is no endometrial thickness cutoff point that provides good diagnostic accuracy and/or reliably excludes the presence of endometrial cancer in patients with postmenopausal bleeding 5.