An aged rat model of partial androgen deficiency: Prevention of both loss of bone and lean body mass by low-dose androgen replacements

The aim of this study was to evaluate the effects of different doses of and rogen replacement, both on body composition and bone,in an aged male orchid ectomized rat model. Testosterone was administered by 0.5, 1, and 2.5-cm sc SILASTIC implants (release of, respectively, 11.5, 23, and 55 mu g/day) to aged (12 months old, +/- 550 g) male orchidectomized Wistar rats during a 15-week experimental period. T 0.5 only partially prevented decrease of ventral prostate and seminal ves icle weight, compared with an intact group that received an empty implant ( Intact). The 1-cm implant (T 1) completely prevented decrease of both semin al vesicles and ventral prostate weight. The 2.5-cm implant (T 2.5) was cle arly supraphysiological, as demonstrated by significant hypertrophy of both androgen-sensitive organs. Serum testosterone was lower in T 0.5 and T 1 ( 0.38 +/- 0.06 ng/ml and 0.92 +/- 0.06 ng/ml, respectively) and higher in T 2.5 (2.4 +/- 0.28 ng/ml), compared with both Intact (1.6 +/- 0.23 ng/ml) an d the baseline group (1.6 +/- 0.11 ng/ml). As expected, orchidectomized rats that received an empty SILASTIC implant h ad significantly lower bone mineral content (-7.9%), apparent density (-5.7 %), and lean body mass (-10.8%), as measured by dual-energy x-ray absorptio metry, without significant changes in body weight and fat mass, compared wi th Intact. Also, cancellous (-50.3%) and cortical (-1.8%) volumetric densit y, as measured by peripheral quantitative computed tomography, were decreas ed in the tibia. Bone turnover, as measured by serum osteocalcin and urinar y deoxypyridinoline excretion, was increased in orchidectomized rats that r eceived an empty SILASTIC implant. T 0.5 prevented all changes, not only in bone mineral content, density, and turnover but also in lean body mass. Moreover, there were no significant d ifferences, for all these parameters, between the different doses of testos terone replacement. In conclusion, low-dose androgen replacement does not lead to lower bone mi neral density, higher bone turnover, and lower lean body mass in aged male rats, whereas complete androgen deficiency does. Therefore, the threshold c oncentration of testosterone necessary for prevention of both bone and lean body mass loss in aged male rats is clearly lower than for prostate and se minal vesicles.