Hypothalamic amenorrhea, a common disorder associated with abnormalities in gonadotropin pulsatility and subsequent estrogen deficiency, is usually transient, and treatment indications are unclear unless fertility is desired. To determine whether this disorder is associated with progressive bone loss, we studied 24 women with primary or secondary amenorrhea related to stress or simple weight loss, compared with 31 normal women of the same age. Amenorrheic women had significantly lower (P=.01) body fat (26.4 ± 7.3 versus 30.6 ± 4.7%) and higher (P=.0001) urine free cortisol levels (250 ± 100 versus 140 ± 50 nmol/day) than normals. Trabecular bone density in women with hypothalamic amenorrhea as assessed by spinal computed tomography was significantly (P=.001) lower than in normals (140.2 ± 27.3 versus 175.1 ± 24.6 mg K2HPO4/mL, respectively). Twenty of the 24 amenorrheic women had initial spinal bone density below the mean in normals, and in eight it was 2 standard deviations or more below the normal mean. Initial bone density correlated negatively with duration of amenorrhea (r=-0.489,P=.02) and positively with serum free testosterone levels (r=0.517,P=.02). Prospective evaluation showed a decline in spinal bone density in those who were amenorrheic for fewer than 5 years. The slope of change in bone density correlated with initial weight, percent ideal body weight, and percent body fat (R2=0.597,P=.0003; R2=0.549,P=.0007; and R2=0.618,P=.0002, respectively). We conclude that in women with hypothalamic amenorrhea: 1) Trabecular osteopenia is common; 2) the greatest risk of progressive bone loss occurs early after the onset of amenorrhea; 3) low levels of androgens may play a role in the development of osteopenia; 4) low indices of body mass predict higher risk for declining bone density; and 5) prolonged amenorrhea can occur. These findings may have implications about the benefit and timing of gonadal steroid replacement in hypothalamic amenorrhea.