Hypogonadism

Men as well as women are at risk of developing osteoporosis that may lead to increased risk of fractures. According to bone density studies in men with low levels of testosterone, hypogonadism is an independent risk factor for osteoporosis. When testosterone is replaced, bone density increases in this population. Bone density is a popular and easy way to measure the degree of osteoporosis, but it does not provide complete information about fracture risk. Alterations of bone architecture, as determined by histomorphometry, also represent increased risk of fracture, even in men with minimal evidence of osteoporosis. Alternative ways to examine bone microarchitecture include quantitative computed tomography and high-resolution magnetic resonance microimaging ([micro]MRI). The latter test has been called "the virtual bone biopsy" and demonstrates the integrity of the trabecular network. Benito and associates used [micro]MRI-based virtual bone biopsy to evaluate the trabecular architecture of bone in severely hypogonadal men compared with a control group of eugonadal men.

Ten men with secondary hypogonadism, diagnosed on the basis of repeat morning serum testosterone levels of less than 8.7 nmol per L, underwent testing of bone mineral density by dual energy x-ray absorptiometry and [micro]MRI of the right distal tibia. The control group was made up of 10 eugonadal men who also were evaluated.

Bone density was decreased among the hypogonadal men, but the difference was not statistically significant. Using a variety of accepted parameters, the [micro]MRI results revealed significantly more deterioration of bone architecture among the hypogonadal men. Participants in both groups were matched by race, age, body mass index, calcium intake, and smoking status, so none of these factors could account for the difference in bone architecture.

The authors conclude that hypogonadal men have increased deterioration of bone architecture that is detectable by [Mu]MRI. This deterioration of bone structure may result in decreased bone strength and greater fracture risk to a degree not clearly indicated by bone density testing.

RICHARD SADOVSKY, M.D.

Benito M, et al. Deterioration of trabecular architecture in hypogonadal men. J Clin Endocrinol Metab April 2003; 88:1497-502.

EDITOR'S NOTE: In recent years, the National Institute on Aging1 has focused on the potential value of testosterone supplementation in men with low levels of testosterone. The panel noted that study results have shown that testosterone replacement in older men has a beneficial effect on bone mineral density, muscle strength, and lean body mass, with decreases in body fat and improvements in lipid profiles. Unfortunately, the results are not consistent among all trials, and testosterone supplementation is not totally benign. The panel concludes that the strongest association exists between clinical hypogonadism and osteoporosis and decreased sexual function. The best way to measure testosterone levels remains uncertain, as do the appropriate numbers to use to represent the lower limit of normal. The potentially serious side effects of testosterone supplementation include (1) increased risk of prostate cancer, (2) increased risk of significant benign prostatic hypertrophy, (3) blood hyperviscosity secondary to erythropoiesis stimulation, (4) increased risk of sleep apnea, (5) possible increased risk of cardiovascular disease, and (6) aggressive behavior or inappropriate sexual behavior. Further studies are needed to identify the usefulness of testosterone supplementation in older men with low levels of serum testosterone. Specific clinical syndromes, including osteoporosis and diminished sexual interest and activity, are becoming accepted indications for carefully monitored testosterone supplementation.--R.S.

REFERENCE

(1.) Thorner M, et al., for the Advisory Panel on Testosterone Replacement in Men. Special report. Report of National Institute on Aging Advisory Panel on Testosterone Replacement in Men. J Clin Endocrinol Metab October 2001;86:4611-4.

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