Men who use muscle-building supplements (MBSs) that contain creatine or androstenedione may have up to 65% increased risk of developing testicular cancer, according to a case-control study published online March 31 in the British Journal of Cancer.
This risk increased even more among men who began using MBSs before age 25, who used various kinds of MBSs, or who used them for a long duration.
The study is the first to look at the epidemiologic associations between MBSs and testicular cancer, the researchers note.
Young people, in particular, use MBSs, and the number of users is increasing, according to senior author Tong Zhang Zheng, MB, ScD, who led the study at Yale University before joining the Brown University School of Public Health as a professor of epidemiology.
"Although no population survey data exist to suggest just what percentage of young people use MBSs, we do know that the MBS business rakes in billions of dollars," Dr Zheng commented in an interview.
Testicular germ cell cancer (TGCC) is the most common solid cancer in men aged 15 to 39 years. The incidence of TGCC has risen in recent decades, climbing from 3.7 of 100,000 in 1975 to 5.9 of 100,000, according to background information in the article.
"The increasing incidence of TGCC is real, not artificially [related to] increased detection or reporting," Dr Zheng explained. "It is unknown what explains the increase. So far, no other known factors [aside from MBSs] can explain even part of the increase."
"No one knows at this stage what ingredients [in MBSs] might be responsible for the increase," Dr Zheng added, "but we do know some of the ingredients in MBSs could cause testis damage."
Natural components in MBSs could act like artificial hormones, Dr Zheng and colleagues mention in the article. Some products could also contain impurities or less active ingredients than those listed on the product label. Still others may contain "hidden" ingredients not listed on the label. Such substances include androgenic steroids, which have been linked to testicular cancer in rats.
Recently, the FDA raised concerns about MBSs. On April 13, the FDA issued a warning about the use of the MBS called Tri-Methyl Xtreme, which contains potentially harmful synthetic anabolic steroids that can cause serious liver injury. In response to reports of adverse events from consumers ― one each in California, New Jersey, and Utah ― the FDA began an investigation to identify the product's manufacturer. No deaths have been reported.
Significant Increase in Risk
The case-control study included 356 men diagnosed with TGCC between 2006 and 2010 and 513 men without testicular cancer. Participants were between the ages of 18 and 55 and lived in Connecticut or Massachusetts. During in-person interviews, trained interviewers asked these men about risk factors for TGCC, such as smoking, drinking, exercise, family history of testicular cancer, undescended testicles, and past injury to the testis or groin. The interviewers also asked about lifetime MBS use, including use of 30 different types of MBS powders or pills. The researchers used product labels to assess major ingredients, including creatine, protein, androstenedione.
The interviews revealed that almost 20% of participants with TGCC had used MBSs.
Men who had taken MBSs had significantly increased odds of developing TGCC (OR = 1.65; 95% CI, 1.11 - 2.46). These odds rose even higher among men who started using MBSs before age 25 (OR = 2.21; 95% CI, 1.34 - 3.63), who used two or more types of MBSs (OR = 2.77; 95% CI, 1.30 - 5.91), or who had taken them for a period longer than 36 months (OR = 2.56; 95% CI, 1.39 - 4.74). The strengths of these associations remained significant even after adjusting for major confounders.
Further analyses suggested that using MBSs containing creatine and proteins significantly increased the risk for TGCC (OR = 2.55; 95% CI; 1.05 - 6.15).
"Considering the magnitude of the association and the observed dose-response trends, MBS use may be an important and modifiable exposure that could have important scientific and clinical importance for preventing TGCC development if this association is confirmed by future studies," the authors conclude.
An international consortium is working to build an understanding about the unclear etiology of testicular cancer.
The authors report no relevant financial relationships.
Br J Cancer. Published online March 31 2015. Veronica Hackethal, MD