March 26, 2020
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Circulating testosterone level drives fracture risk among older men

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Bu Beng Yeap
Bu Beng Yeap

Researchers observed a U-shaped relationship between circulating testosterone levels and fracture risk among a cohort of Australian men, with men with a midrange plasma testosterone concentration at lowest risk for sustaining any fracture or hip fracture during a decade of follow-up, according to findings from a community-based study published in The Journal of Clinical Endocrinology & Metabolism.

Levels of testosterone, rather than estradiol, predict the incidence of fractures in older men,” Bu Beng Yeap, MBBS, FRACP, PhD, professor at the University of Western Australia Medical School and an endocrinologist in the department of endocrinology and diabetes at Fiona Stanley Hospital in Perth, Western Australia, told Healio. “The U-shaped association of testosterone with incidence of fractures indicates that men with low testosterone levels are at higher risk. Men with testosterone levels in the middle of the range have the lowest risk.”

Yeap and colleagues analyzed data from 3,307 men participating in the Health in Men Study, a cohort of men from Perth, Western Australia (mean age, 77 years). Using blood samples collected in 2001-2004 (baseline), researchers assessed plasma testosterone, dihydrotestosterone and estradiol via mass spectrometry, and sex hormone-binding globulin and luteinizing hormone (LH) using immunoassay. Incident fractures occurring after baseline were assessed using the Western Australian Data Linkage System. Researchers used Cox proportional hazard regression models to assess independent associations of quartiles of testosterone, calculated free testosterone, dihydrotestosterone, estradiol, SHBG and LH concentrations with incidence of any fracture or hip fracture, adjusting for age, comorbidities and frailty status.

During a median follow-up of 10.6 years, 330 men sustained any fracture, for a rate of 1.1% per participant per year. Incidence of hip fracture, which occurred among 144 men during follow-up, was 0.5% per participant per year.

Yeap Infographic
Researchers observed a U-shaped relationship between circulating testosterone levels and fracture risk among a cohort of Australian men, with men with a midrange plasma testosterone concentration at lowest risk for sustaining any fracture or hip fracture during a decade of follow-up.

In models adjusted for age and frailty, researchers found that men with testosterone levels in the midrange had the lowest risk for incidence of any fracture compared with men in the lowest testosterone quartile, with adjusted HRs of 0.69 for men in quartile 2 (95% CI, 0.51-0.94) and 0.59 for men in quartile 3 (95% CI, 0.42-0.83). There was no between-group difference for fracture risk among men in the highest testosterone quartile vs. the lowest testosterone quartile. Results were similar in analyses assessing hip fracture risk, with adjusted HRs of 0.6 for men in quartile 2 (95% CI, 0.37-0.93) and 0.52 for men in quartile 3 (95% CI, 0.31-0.88) when compared with men in the lowest testosterone quartile.

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Additionally, men with an SHBG level in the highest quartile were more likely to sustain a hip fracture compared with men in the lowest SHBG quartile, with an adjusted HR of 1.76 (95% CI, 1.05-2.96).

Dihydrotestosterone, estradiol and LH levels were not associated with fracture.

“Randomized clinical trials are needed to see whether treating men who have low testosterone levels would reduce their risk for fracture,” Yeap said. – by Regina Schaffer

For more information:

Bu Beng Yeap, MBBS, FRACP, PhD, can be reached at the Harry Perkins Institute of Medical Research, 11 Robin Warren Drive, Murdoch 6150, Western Australia, Australia; email: bu.yeap@uwa.edu.au.

Disclosures: The authors report no relevant financial disclosures.