application) Anorexia nervosa is becoming increasingly common among young women. Osteopenia is a severe, frequent and often permanent comorbid medical complication of anorexia nervosa which results in debilitating vertebral crush fractures. The pathophysiology of the bone loss is incompletely understood, and no effective therapy exists. The osteopenia that occurs in this population is unique and differs from that of postmenopausal osteoporosis. Data of surrogate markers of bone turnover have shown decreased bone formation in addition to increased resorption seen in states of estrogen deficiency. Our preliminary data demonstrate that women with anorexia nervosa have a relative deficiency of the anabolic hormone testosterone which is known to stimulate bone formation in vitro. We hypothesize that testosterone deficiency, primarily of ovarian origin, contributes to the decreased bone formation and bone density seen in anorexia nervosa. This hypothesis will be tested by investigating whether administration of a physiologic replacement dose of testosterone increases bone formation and bone density in this population. In the first phase of this proposal we plan to investigate the prevalence and pathogenesis of androgen deficiency in women with anorexia nervosa and specifically to determine whether ovarian or adrenal androgens are reduced. In the second phase of the study we will investigate the metabolic effects of testosterone deficiency compared with testosterone repletion on bone markers by randomizing women with anorexia nervosa and testosterone deficiency to receive a physiologic replacement dose of testosterone or placebo for 12 weeks and measuring changes in bone turnover markers. In the third phase of the study, we will examine the effects of administering testosterone on bone density and body mass.
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| Miller, Karen K; Deckersbach, Thilo; Rauch, Scott L et al. (2004) Testosterone administration attenuates regional brain hypometabolism in women with anorexia nervosa. Psychiatry Res 132:197-207 |
