The aim of this study was to test the hypothesis that young women with androgen deficiency due to hypopituitarism would benefit from androgen replacement in the form of dehydroepiandrosterone (DHEA). Five young women, age 15.2-23.1 years, with panhypopituitarism were studied in a 12-month double blind placebo-controlled crossover trial of DHEA replacement in a dose 50 mg/day (Belmar Pharmacy, Lakewood, CO). All had growth hormone (GH), thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH) and antidiuretic hormone deficiencies. Gonadotropin deficiency was complete in three and partial in two. The patients were evaluated at baseline, 6 months and 12 months. Serum hormone levels, body composition, lumbar bone mineral density (BMD), exercise capacity and tests of psychological function were performed. DHEA replacement restored serum DHEA levels to normal, 359.8+/-337 ng/dl (12.5+/-11.7 nmol/l). The Life Situation Survey showed significantly better life satisfaction on DHEA than placebo (110 vs 102, p = 0.05). Trends for improved maximal oxygen uptake (VO2), and decreased percent body fat did not reach statistical significance. In conclusion, androgen replacement with DHEA should be considered in young women with panhypopituitarism. Further studies over longer periods in larger groups of patients are necessary to better evaluate the effects of DHEA replacement on BMD, muscle strength and body composition.