To determine the consequences of corticosteroid treatment in postmenopausal patients with severe hepatitis B surface antigen-negative chronic active hepatitis, the findings in 43 such patients (mean age, 59 +/- 2 yr) were compared retrospectively to those in 46 premenopausal counterparts (mean age, 31 +/- 2 yr) after similar durations of initial (19 +/- 2 vs. 18 +/- 2 mo) and subsequent (48 +/- 8 vs. 63 +/- 11 mo) therapy. Postmenopausal patients entered remission as frequently as premenopausal women during initial treatment (81% vs. 83%, p = 0.9), deteriorated as commonly (7% vs. 7%), and developed drug-related complications as frequently (49% vs. 33%, p = 0.14). Postmenopausal women, however, had a higher cumulative frequency of complications (77% vs. 48%, p less than 0.01) and a greater occurrence of multiple complications (44% vs. 13%, p less than 0.01) than premenopausal counterparts during follow-up. Vertebral compression occurred more frequently (23% vs. 7%, p = 0.05), and lumbar spine densities were below the spontaneous fracture threshold more commonly (85% vs. 22%, p less than 0.002). Longer initial and cumulative durations of therapy were associated with the development of complications. We conclude that initial corticosteroid treatment is as safe and effective in postmenopausal women as in premenopausal counterparts. Postmenopausal women, however, have a higher cumulative frequency of complications long-term and a lower net benefit-risk ratio than comparably treated premenopausal women.