Hyperprolactinemia with amenorrhea and galactorrhea generally has a benign clinical course without treatment. Prolonged amenorrhea due to early surgical castration or premature menopause is, however, associated with reduced bone mass and increased risk of fractures. Previous studies in hyperprolactinemic women suggested an association with decreased cortical bone density. To determine whether hyperprolactinemia is associated with reduced trabecular bone mineral, we studied 13 hyperprolactinemic women and matched normal women by quantitative computed tomographic scans of the vertebral bodies. No patient had taken bromocriptine and one patient had previously unsuccessful transsphenoidal surgery. Each patient was matched with a normal woman on the basis of race, age +/- 52 weeks, parity, exercise, tobacco use, oral contraceptive (OCP) use, and alcohol use. No subject was currently taking OCPs. Calcium, phosphorus, and protein intakes were estimated from a 3-day diet diary. The mean duration of amenorrhea was 98.9 +/- 79.7 (SD) months. The mean height, weight, serum 25-hydroxyvitamin D (25,OHD), serum 1,25 dihydroxyvitamin D [1,25(OH)2D] and daily intakes of calcium, phosphorus, and protein were not different. The bone mineral content for each patient fell within +/- SD of the mean of the normal subjects. The mean bone mineral content (mg K2HPO4 eq/ml) of the patients was 10% less than in the normal subjects (144.6 +/- 31.4 (SD) vs. 160.1 +/- 26.6, P less than 0.05). The slope of the regression of bone mineral content and age (mg K2HPO4 eq/ml X yr) was similar in patients (-2.4 +/- 1.1) and normal subjects (-2.3 +/- 1.0). We conclude that hyperprolactinemia is associated with reduced bone mineral content, but does not necessarily produce persistent acceleration of the age-related decline in bone density.