Bone mineral density in the complete androgen insensitivity and 5α-reductase-2 deficiency syndromes

Context: Subjects with complete androgen insensitivity (CAI) and 5 alpha-reductase-2 deficiency (5 alpha RD-2) are natural human models to study the direct effect of androgens on bone mineral density (BMD). Objective: The objective of this study was to test the hypothesis that androgens have a direct effect on BMD in men. Design: This was a prospective, observational study (1989 - 1999) using dual energy x-ray absorptiometry. Setting: The study was set in an outpatient specialty referral center. Patients or Other Participants: All known subjects with these conditions (12 CAI and 16 5 alpha RD-2) from diverse sociodemographic backgrounds were recruited for the study. Interventions: There were no interventions. Main Outcome Measure: Mean Z score and weight-matched Z score at lumbar spine and femoral neck for CAI and 5 alpha RD-2 subjects were determined. Results: Twelve CAI subjects had mean Z score at L2 - L4 of -2.84 (+/- 0.97, P < 0.001) and a mean weight-matched Z score of -2.52 (+/- 0.94, P < 0.001). The mean Z score at the femoral neck was -1.33 (+/- 0.91, P < 0.001) and the mean weight-matched Z score was -1.10 (+/- 0.82, P = 0.001). Sixteen 5 alpha RD-2 subjects had a mean Z score at L2 - L4 of -0.84 (+/- 1.29, P = 0.02) and a mean weight-matched Z score for 15 of 16 patients of -0.44 (+/- 1.08, P = 0.14). The mean Z score at the femoral neck was 0.14 (+/- 1.02, P = 0.58) and the mean weight-matched Z score for 15 of 16 patients was 0.49 (+/- 0.94, P = 0.06). Therefore, in CAI subjects, BMD was significantly decreased in the spine and hip. 5 alpha RD-2 subjects had normal BMD values. Conclusions: 1) Androgens are of direct importance in the development and/ or maintenance of BMD; and 2) testosterone and/or low levels of dihydrotestosterone appear to be sufficient for BMD development and/or maintenance.