Any bleeding in postmenopausal women not taking exogenous estrogen must be investigated. Vaginal, cervical, and rectal bleeding must be distinguished from uterine bleeding. Endometrial sampling is warranted in all postmenopausal women not on estrogen with uterine bleeding. The role of ultrasound in management continues to evolve: Many clinicians find it acceptable to defer biopsy if the endometrial thickness is less than 5 mm in diameter. In women not taking estrogen, the most common cause of uterine bleeding is endometrial atrophy.

Bleeding in postmenopausal women taking estrogen is more problematic. In women on sequential estrogen and progestogen, bleeding should occur only near the end or following the course of progestogen. If such is the case, endometrial sampling never may be indicated. An endometrial biopsy is warranted for bleeding at any other time. Despite the fact that a very few cases of endometrial cancer are associated with endometrial thickness of less than 5 mm in diameter on ultrasound, some clinicians are choosing to evaluate women with unscheduled bleeding by ultrasound alone.

When to sample women on continuous estrogen and progestogen is less clear. Sampling for bleeding occurring during the first 6 months it is administered is rarely necessary. After the initial 6 months, any bleeding warrants biopsy. Biopsy would seem to be indicated at yearly intervals for women who continue to have some bleeding on continuous estrogen and progestogen.

A recent systematic review concluded that irregular bleeding was more than twice as common with a continuous as opposed to a sequential regimen, but with longer duration of treatment, continuous combined therapy was more protective than sequential therapy in preventing endometrial hyperplasia.206 There was also evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen every 3 months) compared to monthly sequential therapy.