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Submitted on June 21, 2004
Accepted on December 12, 2004
*Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114
* To whom correspondence should be addressed. E-mail: KKMiller{at}Partners.org.
Anorexia nervosa (AN) is complicated by severe bone loss, cognitive function deficits, and a high prevalence of major depression. We hypothesized that bone formation would increase, and depressive symptoms and spatial cognition would improve with short-term physiologic testosterone administration. We randomized 33 women with AN and relative testosterone deficiency to transdermal testosterone (Intrinsa, Procter and Gamble Pharmaceuticals, Cincinnati, OH), 150 mcg, 300 mcg or placebo, for three weeks. At baseline, free testosterone correlated with L4 bone density (r=0.51, P < 0.001), BMI (r=0.39, P = 0.02), depressive symptoms (r0.44, P = 0.02), and spatial cognition (r=0.45, P = 0.04). C-terminal propeptide of type 1 collagen (PICP) levels were higher during testosterone administration than placebo (P = 0.03). The change in PICP correlated with change in free testosterone over three weeks (r=0.50, P = 0.02). Osteocalcin and bone specific alkaline phosphatase did not change. Depressed patients receiving testosterone improved from severely depressed to moderately depressed; the placebo group was unchanged (P = 0.02). Spatial cognition improved in the testosterone group compared with placebo (P = 0.0015). Therefore, short-term low-dose testosterone may improve depressive symptoms and spatial cognition in women with AN. Low-dose testosterone may also prevent decreased bone formation in AN, but as testosterone did not affect all markers of bone formation studied, further data are needed.
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