17β-Hydroxyestra-4,9,11-trien-3-one (Trenbolone) preserves bone mineral density in skeletally mature orchiectomized rats without prostate enlargement

Testosterone enanthate (TE) administration attenuates bone loss in orchiectomized (ORX) rats. However, testosterone administration may increase risk for prostate/lower urinary tract related adverse events and polycythemia in humans. Trenbolone enanthate (TREN) is a synthetic testosterone analogue that preserves bone mineral density (BMD) and results in less prostate enlargement than testosterone in young ORX rodents. The purpose of this experiment was to determine if intramuscular TREN administration attenuates bone loss and maintains bone strength, without increasing prostate mass or hemoglobin concentrations in skeletally mature ORX rodents. Forty, 10 month old male F344/Brown Norway rats were randomized into SHAM, ORX, ORX + TE (7.0 mg/week), and ORX + TREN (1.0 mg/week) groups. Following surgery, animals recovered for 1 week and then received weekly: vehicle, TE, or TREN intramuscularly for 5 weeks. ORX reduced total and trabecular (t) BMD at the distal femoral metaphysis compared with SHAMs, while both TREN and TE completely prevented these reductions. TREN treatment also increased femoral neck strength by 28% compared with ORX animals (p < 0.05), while TE did not alter femoral neck strength. In addition, TE nearly doubled prostate mass, compared with SHAMs (p < 0.05). Conversely, TREN induced a non-significant 20% reduction in prostate mass compared with SHAMs, ultimately producing a prostate mass that was 64% below that found in ORX + TE animals (p < 0.01). Hemoglobin concentrations and levator ani/bulbocavernosus (LABC) muscle mass were elevated in ORX + TE and ORX + TREN animals to a similar degree above both SHAM and ORX conditions (p < 0.01). In skeletally mature rodents, both high-dose TE and low-dose TREN completely prevented the ORX-induced loss of tBMD at the distal femoral metaphysis and increased LABC mass. TREN also augmented femoral neck strength and maintained prostate mass at SHAM levels. These findings indicate that TREN may be an advantageous agent for future clinical trials evaluating agents capable of preventing bone loss resulting from androgen deficiency.

► Trenbolone is a non-aromatizable, non-5α reducible synthetic testosterone analogue.
► Testosterone and trenbolone equally preserved bone mineral density after orchiectomy.
► Trenbolone increased femoral neck strength following orchiectomy.
► Testosterone and trenbolone equally elevate hemoglobin concentrations.
► Unlike testosterone, trenbolone did not induce prostate enlargement.