Postmenopausal women who choose hormone replacement therapy (HRT) often discontinue this therapy within 1 year. Few studies have considered why older women (aged > or =65 years) discontinue therapy. To investigate this question and its relationship to HRT-related side effects, we analyzed data collected during the 3-month open-label (active HRT and alendronate placebo) run-in phase of a clinical trial for osteoporosis prevention and treatment in older women. Among women discontinuing the trial, we ascertained a primary reason based on the patients' records and classified it as related or unrelated to HRT. The incidence of specific HRT-related side effects reported during the run-in phase was abstracted from the trial database and compared between patients continuing in the trial and those discontinuing for HRT-related reasons. Of the 485 women who began the 3-month run-in phase, 112 (23%) discontinued the trial. Specifically, 73 (15%) women discontinued for reasons considered HRT related. Breast swelling/tenderness (26 women) and bloating (9 women) were more often primary reasons for discontinuation than were bleeding or spotting (7 women). Comparing all reported side effects, bloating was more common in women discontinuing because of HRT than in women continuing in the trial (18% versus 3%, p < or = 0.001), whereas other complaints were similar or lower: breast swelling/tenderness (59% versus 67%, p > 0.05), bleeding (16% versus 17%, p > 0.05), spotting (23% versus 41%, p < or = 0.05). Bloating, of which women discontinuing complained significantly more often, and breast swelling/tenderness, the most frequently cited primary reason for discontinuation, may be more important factors than bleeding or spotting in an older woman's decision to discontinue HRT.