Reduced levels of the sex hormones testosterone and estrogen raised the risk of low bone density in men 45 and older, a large study using a representative sample of U.S. men found. The study will be presented Sunday, June 3, at The Endocrine Society’s 89th Annual Meeting in Toronto.

The researchers, from The Johns Hopkins University School of Medicine and Bloomburg School of Public Health in Baltimore, said the results suggest another way to identify those at risk of the bone-thinning disease osteoporosis before it can cause fractures. Often thought of as solely a woman’s disease, osteoporosis is underdiagnosed in men and sometimes has more severe consequences. Men have twice the rate of death from hip fractures as do women, said Dr. Channing Paller, study presenter and a second-year internal medicine resident at Johns Hopkins.

Declining bone mineral density is a major cause of hip fractures but requires medical imaging to be detected. The definitive diagnostic test is a bone scan called dual-energy X-ray absorptiometry, or DEXA. Levels of sex hormones are measured with a blood test.

Paller’s group sought to identify what factors lead to a loss in bone density among men. The researchers used data from 1,220 adult men who participated in the Third National Health and Nutrition Examination Survey, or NHANES III, a survey of more than 30,000 Americans. These subjects had provided DEXA bone density measurements as well as blood samples. Among the hormones measured in the blood were testosterone and the predominantly female hormone estrogen, which is present in smaller quantities in men than in women. They looked at the free forms of these hormones, which Paller said is a better measure than total testosterone of the amount available to bind to bones.

Through statistical analysis, Paller’s team found that low levels of both free testosterone and free estrogen were strongly associated with osteopenia—low bone mass that is often a precursor to osteoporosis. The risk of low bone density was highest in middle-aged and older men whose free estrogen levels were in the lowest 25 percent. In men, testosterone can convert to estrogen, so those with low testosterone also had low estrogen levels.

“The study result begs the question of whether we should be treating men who have low testosterone,” said Dr. Adrian Dobs, professor of medicine and oncology at Johns Hopkins and the principal investigator. “Our data suggest that treating men who have low testosterone with replacement therapy would be beneficial for their bones.”

However, not all the men who had low testosterone as defined in the study had the clinical definition of hypogonadism—insufficient production of sex hormones.

The research was funded by the Maryland Cigarette Restitution Fund at Johns Hopkins.

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