Characteristics of hormone replacement therapy

Sequential HRT is characterised by the regular occurrence of bleeding after estrogen and progestogen withdrawal, whereas continuous sequential HRT is characterised by bleeding shortly before or after the end of progestogen insertion. Initially, the occurrence of bleeding after day 11 of progestogen insertion or thereafter was thought to correlate with normal endometrial status, and the presence of proliferative endometrium or hyperplasia was suspected in women who bled earlier.

However, the occurrence of regular bleeding is not evidence of a normal endometrium. Proliferative endometrium has also been diagnosed in women who bleed regularly. Some women have irregular bleeding, others do not bleed at all during periods of cyclical withdrawal of therapy and this is not an expression of endometrial pathology, but causes concern for the patient and the doctor. The relationship of the timing of withdrawal bleeding on scv therapy to the occurrence of endometrial proliferation has also not been demonstrated.

A retrospective study evaluating incidents of abnormal bleeding and corresponding endometrial images among patients of the Menopause Study Group showed endometrial proliferation in 20% of women using unbalanced oestrogens and observed more days of bleeding than in patients without proliferation. In ETZ users, the positive predictive value of diagnosing amenorrhea as absence of proliferation was 95%. However, irregular bleeding did not determine the occurrence of endometrial proliferation during E-P therapy.