Severity of Osteopenia in Estrogen-Deficient Women With Anorexia Nervosa and Hypothalamic Amenorrhea

Abstract

Osteopenia of widely varying degree is seen in premenopausal women who are amenorrheic. Osteoporosis is especially severe and complicated by fractures in women with anorexia nervosa (AN). In contrast, clinical fractures are rare in conditions such as hyperprolactinemia and hypothalamic amenorrhea (HA). Factors other than estrogen deficiency may be important in determining the extent of osteopenia. This study was designed to address whether more severe bone loss is found in women with AN independently of the duration of amenorrhea, possibly because of undernutrition. Bone loss was estimated by dual-energy x-ray absorptiometry in 30 amenorrheic women with AN and 19 age-matched women with HA. The two groups were similar with regard to the duration of amenorrhea, previous estrogen use, and age at menarche. Thirty healthy, age-matched women with normal menstrual function served as a control group. Body mass indices were significantly greater in women with HA than in those with AN, as were levels of insulin-like growth factor and percentages of body fat and lean body mass. Bone density of the lumbar spine, total hip, and total body was lowest in the AN group but was also reduced in women with HA compared with eumenorrheic women (Fig. 1). More than 85 percent of women with AN and fewer than 40 percent of those with HA had spinal bone density more than 1 standard deviation below the expected value. Differences in bone density remained significant after allowing for age at menarche, duration of amenorrhea, and previous estrogen use. In amenorrheic women in general and the group with AN in particular, lean body mass was most predictive of bone density at all sites on multivariate analysis. In women with HA, bone density measured at the lumbar spine correlated with body weight and duration of amenorrhea. FIGUREFig. 1: The t scores for lumbar and total hip bone densities in normal controls (white;N = 30) and patients with hypothalamic amenorrhea (HA) (hatched;N = 19) and anorexia nervosa (AN) (black; N= 30). ‡, P < .01 vs. controls; §, P < .001 vs. controls; ¶, P < .0001 vs. controls; §§, P < .001 vs. HA; ¶¶, P < .0001 vs. HA. Results are the mean ± SEM.Women with AN have more severe bone loss than those with HA, and the difference reflects a clinically relevant disparity in risk of fracture. Nutritional factors, especially lean body mass, seem to be a more important reason for these differences than estrogen deficiency. J Clin Endocrinol Metab 1999;84:2049–2055