Treatment of hypogonadal men with testosterone
has been shown to ameliorate the effects of testosterone deficiency on bone,
muscle, erythropoiesis, and the prostate. Most previous studies, however,
have employed somewhat pharmacological doses of testosterone esters, which
could result in exaggerated effects, and/or have been of relatively short
duration or employed previously treated men, which could result in dampened
effects.
The goal of this study was to determine the
magnitude and time course of the effects of physiological testosterone
replacement for 3 yr on bone density, muscle mass and strength,
erythropoiesis, prostate volume, energy, sexual function, and lipids 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 previously been treated for hypogonadism. We
treated them with testosterone transdermally for 3 yr. Sixteen men completed
12 months of the protocol, and 14 men completed 36 months. The mean serum
testosterone concentration reached the normal range by 3 months of treatment
and remained there for the duration of treatment.
Bone mineral density of the lumbar spine
(L2–L4) increased by 7.7 ± 7.6% (P < 0.001), and that of the femoral
trochanter increased by 4.0±5.4% (P=0.02); both reached maximum values by
24 months. Fat-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 decrease in fat mass was not statistically significant.
Strength of knee flexion and extension did
not change. Hematocrit increased dramatically, from mildly 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. Prostate volume also increased
dramatically, from subnormal (12.0 ± 6.0 mL) before treatment to normal
(22.4 ± 8.4 mL; P = 0.004), principally during the 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 increased, 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, prostate volume, erythropoiesis, energy, and sexual
function. The full effect of testosterone 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 for
monitoring the magnitude and the time course of the effects of testosterone
replacement in hypogonadal men.
Citation:
J Clin Endocrinol Metab 2000: 85; 2670–2677
