Androgens and bone density in women with hypopituitarism

Hypopituitarism is associated with osteopenia and a reduction in lean body mass. We have recently demonstrated markedly reduced serum androgen levels in women with hypopituitarism. We hypothesized that serum androgen levels and lean body mass are important determinants of bone mineral density (BMD) in women with hypopituitarism. In addition, because IGF-I may stimulate androgen secretion in women, we investigated whether GH administration results in an increase in serum androgen levels. Sixteen women with a history of pituitary disease of adult-onset and serum GH levels less than 5 ng/ml on stimulation testing underwent BMD and body composition testing by dual-energy x-ray absorptiometry. Univariate regression analysis revealed strong correlations between androgen levels and BMD [lateral spine BMD and dehydroepiandrosterone sulfate (DHEAS) (r = 0.68, P = 0.03), total hip BMD and free T (r = 0.60, P = 0.01), Ward's triangle BMD and DHEAS (r = 0.68, P = 0.004), Ward's triangle BMD and free T (r = 0.54, P = 0.03), femoral neck BMD and free T (r = 0.52, P = 0.04), and femoral neck BMD and DHEAS (r = 0.51, P = 0.04)]. When adjusted for age using Z scores, correlations at the femoral neck no longer reach significance. Correlations between androgens and BMD at other sites, including anterior-posterior spine and total body, were not significant, and neither total T nor androstenedione correlated with BMD at any site. Lean body mass strongly correlated with BMD [total hip (r = 0.80, P = 0.0002), total body (r = 0.78, P = 0.0003), trochanter (r = 0.74, P = 0.001), Ward's triangle (r = 0.56, P = 0.02), femoral neck (r = 0.53, P = 0.04), and anterior-posterior spine (r = 0.52, P = 0.04)]. In stepwise regression models, DHEAS determined 47% of the variation in Ward's triangle BMD (R(2) = 0.47, P = 0.004) and 46% of lateral spine BMD (R(2) = 0.46, P = 0.03). Lean body mass determined 64% of the variation in total hip BMD (R(2) = 0.64, P = 0.0002), 62% of total body (R(2) = 0.62, P = 0.0003), and 55% of trochanter BMD (R(2) = 0.55, P = 0.001). Subjects were then randomized to receive GH at a dose of 12.5 microg/kg per day or placebo for 12 months in a double-blind protocol. Serum androgen levels were obtained at baseline, 1, 3, 6, 9, and 12 months after initiation of GH. Androgen levels did not increase in the women receiving GH for 12 months, compared with those receiving placebo. Stimulation of androgen secretion is therefore unlikely to be a mechanism underlying the improvement in BMD, body composition, or quality of life observed with GH administration. In conclusion, androgen levels and lean body mass may be important determinants of BMD in women with hypopituitarism. It remains to be determined whether androgen replacement therapy itself or an increase in lean body mass achieved as a result of androgen administration will result in an improvement in BMD in this population.