Men who take muscle-building supplements, such as creatine or androstenedione, are far more likely to develop testicular cancer than those who do not use such products, new research shows.

According to the study, published in the British Journal of Cancer, the associated cancer risk is especially high among men who start using supplements before age 25, those who use multiple supplements, and those who use them for years.

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"The observed relationship was strong," said Tongzhang Zheng, who led the study at Yale University before recently joining the Brown University School of Public Health as a professor of epidemiology.

"If you used at earlier age, you had a higher risk. If you used them longer, you had a higher risk. If you used multiple types, you had a higher risk."

Testicular cancer rates have increased over the past four decades — rising to 5.9 cases per 100,000 men in 2011, from 3.7 cases in 100,000 in 1975 — for reasons researchers don’t fully understand

"Testicular cancer is a very mysterious cancer," Zheng said. "None of the factors we've suspected can explain the increase."

The new study is the first to link supplements and testicular cancer, and was prompted by growing evidence that that at least some supplement ingredients may damage the testes, the researchers said.

"Our study found that supplement use was related to a higher risk of developing testicular cancer. These results are important because there are few identified modifiable risk factors for testicular cancer," said Russ Hauser, professor of environmental health science at the Harvard School of Public Health and a main collaborator of the research.

The findings are based on detailed interviews of nearly 900 men from Massachusetts and Connecticut — 356 of whom had been diagnosed with testicular cancer.

The researchers asked the men about their supplement use and a wide variety of other possible factors such as smoking, drinking, exercise habits, family history of testicular cancer, and prior injury to their testes or groin.

The results showed the men who used supplements at least one supplement weekly for at least a month had 65 percent greater risk of having developed testicular cancer compared to the men who did not use supplements. The risks were greater for men who used multiple supplements, took them for three years or longer, and who were 25 years old or younger when they started taking them

"Considering the magnitude of the association and the observed dose-response trends, muscle-building supplements use may be an important and modifiable exposure that could have important scientific and clinical importance for preventing testicular germ cell cancer development if this association is confirmed by future studies," the authors concluded.