Bone Mineral Density in the Complete Androgen Insensitivity and 5α-Reductase-2 Deficiency Syndromes

Abstract

Subjects with complete androgen insensitivity (CAI) and 5alpha-reductase-2 deficiency (5alphaRD-2) are natural human models to study the direct effect of androgens on bone mineral density (BMD). The objective of this study was to test the hypothesis that androgens have a direct effect on BMD in men. This was a prospective, observational study (1989-1999) using dual energy x-ray absorptiometry. The study was set in an outpatient specialty referral center. All known subjects with these conditions (12 CAI and 16 5alphaRD-2) from diverse sociodemographic backgrounds were recruited for the study. There were no interventions. Mean Z score and weight-matched Z score at lumbar spine and femoral neck for CAI and 5alphaRD-2 subjects were determined. 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 5alphaRD-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. 5alphaRD-2 subjects had normal BMD values. 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.