Effect on bone health of estrogen preparations in premenopausal women with anorexia nervosa: A systematic review and meta-analyses

Objective: Because estrogen therapies are widely prescribed for amenorrhea associated with anorexia nervosa (AN), we conducted a systematic review and meta-analyses to estimate the influence of estrogen preparations (EP) on bone mineral density in women with AN. Method: Prospective cohort studies and randomized clinical trials (RCTs) comparing the effect of EP use to no treatment or placebo on bone mineral density and bone fractures were included. Independent reviewers selected studies for inclusion and extracted study characteristics, markers of methodologic quality, and outcomes for the intentionto-treat population. Results: Using random-effects metaanalyses and inconsistency across trials using the I² statistic, data were combined across two eligible prospective cohort studies and four RCTs; none reported effects on bone fractures. Compared with placebo or no treatment, low quality evidence found EPs have a moderate effect on bone mineral density in the lumbar spine [ES (effect size) 0.33, 95% CI (confidence interval) 0.09, 0.56; I² = 0%)], but no significant effect on the femoral neck (ES 0.13, 95% CI -0.16, 0.43; I² = 0%). There were no significant treatment-subgroup interactions. Discussion: In general, EPs have uncertain benefit and should be avoided by women with AN in whom the success of weight and nutritional rehabilitation is judged by menses resumption.