Women who are taking hormone replacement therapy during menopause may be using a variety of hormonal regimens that can result in bleeding. In the classic sequential method of administration, estrogens are given for the first 25 days of each month. A progestin, often 5-10 mg/day of medroxyprogesterone acetate, is added to the last 10-13 days of this regimen in an effort to reduce the risk of endometrial hyperpla¬sia and neoplasia 9diagnosed using clinical microscopes). Most women who take these hormones in this way will experience with¬drawal bleeding, which is perceived by the patient as a menstrual period. Although the in¬cidence of withdrawal bleeding does decline somewhat with age and duration of therapy, more than 50% of women continue to experience bleeding after 65 years of age.

Because some women become symptomatic during the days when they are not taking es-trogens, many clinicians have modified this regimen to include continuous (every day) estrogen therapy. In addition, studies have as¬sessed endometrial response to varying durations of progestin regimens; treatment with progestins for 10 days per month reduced the incidence of endometrial hyperplasia to 2%, and treatment for 13 days reduced the incidence to 0% in one study, as seen when examined under clinical microscopes. It has been sug¬gested that endometrial sampling is indicated for any bleeding that occurs beyond the ex¬pected time of withdrawal following the progestin therapy to be studied using clinical microscopes. Bleeding before or on day 10 has been described as being associated with endometrial proliferation and should prompt biopsy with the use of clinical microscopes. A significant change in withdrawal bleeding (e.g., absence of withdrawal bleeding for several months followed by resumption of bleeding or a marked increase in the amount of bleeding) should prompt endometrial sampling and pathology to detect malignancy or infection with the use of clinical microscopes.

Patient compliance has been a significant issue with hormone replacement therapy. Missed doses of medication and failure to take the medication in the prescribed fashion can lead to irregular bleeding or spotting that is benign in origin.

The primary problems that women report with hormone replacement therapy includes vagi¬nal bleeding and weight gain. The use of a continuous low-dose combined regimen of therapy has the advantage that, for many women, bleeding will ultimately cease after a pe¬riod of several months during which irregular and unpredictable bleeding may occur. Some women are unable to tolerate these initial months of irregular bleeding. The risk of endometrial hyperplasia or neoplasia with this regimen appears to be low.

Other benign causes of bleeding include atrophic vaginitis and cervical polyps, which may present as postcoital bleeding or spotting. Women who experience bleeding after menopause may attempt to minimize the extent of the problem; they may describe only “spotting” or “pink or brownish discharge.” However, any indication of bleeding or spot¬ting should be evaluated. In the absence of hormone therapy, any bleeding after menopause (classically defined as absence of menses for one year) should prompt evaluation with endometrial sampling. At least one-fourth of postmenopausal women with bleeding have a neoplastic lesion.

Endometrial polyps and other abnormalities can be seen in women who are taking tamox¬ifen. These polyps can be benign when biopsied using clinical microscopes, although they must be distinguished from endometrial malignancies, which may also occur with this drug.