Premenopausal amenorrheic women may be at risk for the development of osteoporosis. In hyperprolactinemia, cortical bone mass is decreased and the magnitude of the decrease correlates with the severity of the estrogen deficiency. However, bone loss in women with amenorrhea from other causes has not been assessed. We have studied women with hypothalamic and hyperprolactinemic amenorrhea and premature ovarian failure. Bone mass in the peripheral cortical bone was only slightly decreased from age-matched controls, but spinal trabecular bone was decreased 20% to 30%. Estradiol levels were 20 to 80 pg/mL in these women, not different from normal early follicular levels. The decrease in bone mass in the spine did not correlate with serum estradiol at these levels. The hypothalamic amenorrhea group was made up of athletes in whom the bone mass decrease was an unexpected finding.