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An Aged Rat Model of Partial Androgen Deficiency: Prevention of Both Loss of Bone and Lean Body Mass by Low-Dose Androgen Replacement¹

Laboratory for Experimental Medicine and Endocrinology (D.V., L.V., E.V.H., J.V.S., R.B.), Onderwijs en Navorsing, Gasthuisberg and Centre for Metabolic Bone Diseases (S.B.), Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

Address all correspondence and requests for reprints to: D. Vanderschueren, Laboratory for Experimental Medicine and Endocrinology, Herestraat 49, B-3000 Leuven, Belgium. E-mail: dirk.vanderschueren{at}uz.kuleuven.ac.be

The aim of this study was to evaluate the effects of different doses of androgen replacement, both on body composition and bone, in an aged male orchidectomized rat model. Testosterone was administered by 0.5, 1, and 2.5-cm sc SILASTIC implants (release of, respectively, 11.5, 23, and 55 µg/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 vesicle weight, compared with an intact group that received an empty implant (Intact). The 1-cm implant (T 1) completely prevented decrease of both seminal vesicles and ventral prostate weight. The 2.5-cm implant (T 2.5) was clearly 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) and the baseline group(1.6 ± 0.11 ng/ml).

As expected, orchidectomized rats that received an empty SILASTIC implant had significantly lower bone mineral content (-7.9%), apparent density (-5.7%), and lean body mass (-10.8%), as measured by dual-energy x-ray absorptiometry, without significant changes in body weight and fat mass, compared with Intact. Also, cancellous (-50.3%) and cortical (-1.8%) volumetric density, as measured by peripheral quantitative computed tomography, were decreased in the tibia. Bone turnover, as measured by serum osteocalcin and urinary deoxypyridinoline excretion, was increased in orchidectomized rats that received 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 differences, for all these parameters, between the different doses of testosterone replacement.

In conclusion, low-dose androgen replacement does not lead to lower bone mineral density, higher bone turnover, and lower lean body mass in aged male rats, whereas complete androgen deficiency does. Therefore, the threshold concentration of testosterone necessary for prevention of both bone and lean body mass loss in aged male rats is clearly lower than for prostate and seminal vesicles.

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