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Testosterone Administration in Women with Anorexia Nervosa

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Karen K. Miller, M.D., Neuroendocrine Unit, BUL 457B, Massachusetts General Hospital, Boston, Massachusetts 02114. 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 physiological testosterone administration. We randomized 33 women with AN and relative testosterone deficiency to transdermal testosterone (Intrinsa, Procter and Gamble Pharmaceuticals, Cincinnati, OH), 150 µg, 300 µg, or placebo, for 3 wk. At baseline, free testosterone correlated with L4 bone density (r = 0.51, P < 0.001), body mass index (r = 0.39, P = 0.02), depressive symptoms (r = –0.44, P = 0.02), and spatial cognition (r = 0.45, P = 0.04). C-terminal propeptide of type 1 collagen levels were higher during testosterone administration than placebo (P = 0.03). The change in propeptide of type 1 collagen correlated with change in free testosterone over 3 wk (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 because testosterone did not affect all markers of bone formation studied, further data are needed.

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