Effects of testosterone replacement in androgen-deficient women with hypopituitarism: A randomized, double-blind, placebo-controlled study

Context: Hypopituitarism in women is characterized by profound androgen deficiency due to a loss of adrenal and/or ovarian function. The effects of testosterone replacement in this population have not been reported. Objective: The objective of the study was to determine whether physiologic testosterone replacement improves bone density, body composition, and/or neurobehavioral function in women with severe androgen deficiency secondary to hypopituitarism. Design: This was a 12-month randomized, placebo-controlled study. Setting: The study was conducted at a general clinical research center. Study Participants: Fifty-one women of reproductive age with androgen deficiency due to hypopituitarism participated. Intervention: Physiologic testosterone administration using a patch that delivers 300 mu g daily or placebo was administered. Main Outcome Measures: Bone density, fat-free mass, and fat mass were measured by dual x-ray absorptiometry. Thigh muscle and abdominal cross-sectional area were measured by computed tomography scan. Mood, sexual function, quality of life, and cognitive function were assessed using self-administered questionnaires. Results: Mean free testosterone increased into the normal range during testosterone administration. Mean hip ( P = 0.023) and radius ( P = 0.007), but not posteroanterior spine, bone mineral density increased in the group receiving testosterone, compared with placebo, as did mean fat-free mass ( P = 0.040) and thigh muscle area ( P = 0.038), but there was no change in fat mass. Mood ( P = 0.029) and sexual function ( P = 0.044) improved, as did some aspects of quality of life, but not cognitive function. Testosterone at physiologic replacement levels was well tolerated, with few side effects. Conclusions: This is the first randomized, double-blind, placebo-controlled study to show a positive effect of testosterone on bone density, body composition, and neurobehavioral function in women with severe androgen deficiency due to hypopituitarism.