Context: There is a compelling need for therapies that prevent, defer the onset, slow the progression, or improve the symptoms of Alzheimer disease (AD).

Objective: To evaluate the effects of testosterone therapy on cognition, neuropsychiatric symptoms, and quality of life in male patients with mild AD and healthy elderly men.

Design: Twenty-four-week, randomized, double-blind, placebo-controlled, parallel-group study.

Setting: Memory disorders clinics as well as general neurology and medicine clinics from University of California medical centers at Los Angeles, San Francisco, and Irvine.

Patients or other participants: Sixteen male patients with AD and 22 healthy male control subjects. Healthy elderly control men were recruited from the community through advertisements as well as through the university-based clinics.

Intervention: Testosterone and placebo, in the form of hydroalcoholic gel (75 mg), were applied daily to the skin of the participants.

Main outcome measures: Instruments assessing cognitive functioning (Alzheimer's Disease Assessment Scale-Cognitive Subscale, California Verbal Learning Test, Block Design Subtest, Judgment of Line Orientation, Developmental Test of Visual-Motor Integration), neuropsychiatric symptoms (Neuropsychiatric Inventory), global functioning (Clinician's Interview-Based Impression of Change), and quality of life (Quality of Life-Alzheimer Disease Scale).

Results: For the patients with AD, the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality-of-life scale (P = .01). No significant treatment group differences were detected in the cognitive scores at end of study, although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo. In the healthy control group, a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group (P = .09) compared with placebo treatment. No difference between the treatment groups was detected in the remaining outcome measures. Testosterone treatment was well tolerated with few adverse effects relative to placebo.

Conclusions: Results suggest that testosterone replacement therapy improved overall quality of life in patients with AD. Testosterone had minimal effects on cognition.