Effects of testosterone replacement in hypogonadal men

Treatment of hypogonadal men with testosterone has been shown to ameliorate the effects of testosterone deficiency on bone, muscle, erythropoiesis, an d the prostate. Most previous studies, however, have employed somewhat phar macological doses of testosterone esters, which could result in exaggerated effects, and/or have been of relatively short duration or employed previou sly treated men, which could result in dampened effects. The goal of this s tudy was to determine the magnitude and time course of the effects of physi ological testosterone replacement for 3 yr on bone density, muscle mass and strength, erythropoiesis, prostate volume, energy, sexual function, and li pids in previously untreated hypogonadal men. We selected 18 men who were hypogonadal (mean serum testosterone +/- SD, 78 +/- 77 ng/dL; 2.7 +/- 2.7 nmol/L) due to organic disease and had never pre viously been treated for hypogonadism. We treated them with testosterone tr ansdermally for 3 yr. Sixteen men completed 12 months of the protocol, and 14 men completed 36 months. The mean serum testosterone concentration reach ed the normal range by 3 months of treatment and remained there for the dur ation of treatment. Bone mineral density of the lumbar spine (L2-L4) increa sed by 7.7 +/- 7.6% (P < 0.001), and that of the femoral trochanter increas ed by 4.0 +/- 5.4% (P = 0.02); both reached maximum values by 24 months. Fa t-free mass increased 3.1 kg (P = 0.004), and fat-free mass of the arms and legs individually increased, principally within the first 6 months. The de crease in fat mass was not statistically significant. Strength of knee flex ion and extension did not change. Hematocrit increased dramatically, from m ildly anemic (38.0 +/- 3.0%) to midnormal (43.1 +/- 4.0%; P = 0.002) within 3 months, and remained at that level for the duration of treatment. Prosta te volume also increased dramatically, from subnormal (12.0 +/- 6.0 mt) bef ore treatment to normal (22.4 +/- 8.4 mt; P = 0.004), principally during th e first 6 months. Self-reported sense of energy (49 +/- 19% to 66 +/- 24%; P = 0.01) and sexual function (24 +/- 20% to 66 +/- 24%; P < 0.001) also in creased, principally within the first 3 months. Lipids did not change. We conclude from this study that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip, fat-free mass, prostat e volume, erythropoiesis, energy, and sexual function. The full effect of t estosterone on bone mineral density took 24 months, but the full effects on the other tissues took only 3-6 months. These results provide the basis fo r monitoring the magnitude and the time course of the effects of testostero ne replacement in hypogonadal men.