A 2015 study finds a significant association between muscle-building supplements (MBS) and testicular germ cell carcinoma (TGCC) with seemingly massive odds ratios. There was a wave of panic about this study along with a lot of low-quality discussion (immediate dismissal due to grouping creatine and steroids, vows to immediately quit creatine, etc) on reddit and (unsurprisingly) supplement sites, but little after that. I think this study has a lot of public importance given rising testicular cancer and the prevalence of supplements, and that it's a huge shame that the vast majority of information you can find discussing it is so low-quality and biased.
The main thing that disturbs most people, including me, is the association with creatine, as risks with steroids are much more widely accepted (i.e., "is this the next asbestos?") There are a few things in particular I'm confused about.
To begin with, to summarize what I perceive to be the "relevant, important bits".
In the "Study population" section:
The eligibility criteria for cases in the study included having a histologically confirmed TGCC (Stage 0–IV) diagnosed during 2006–2010, no previous cancer diagnoses except for non-melanoma skin cancer, being a male resident of CT or MA and between the ages of 18–55 at diagnosis (...) Population-based controls were identified among English-speaking male residents of CT and MA between the ages of 18–55 at the time of the interview.
MBS use was defined as use for at least once a week for X4 consecutive weeks. The interview included an assessment of 30 different types of MBS powders or pills. The major ingredients, including creatine, protein, and androstenedione or its booster, were abstracted according to the product ingredients.
In the "Statistical analysis" section:
Unconditional logistic regression models were used to evaluate the associations between the use of MBS and the risk of TGCC. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated for ever vs never MBS use and for several additional metrics in relation to risk of TGCC. These metrics included age at first use, number of MBS products used, and duration of use.
In the "Results" section:
We further conducted exploratory stratified analyses examining associations with TGCC for the major types of MBS use reported by the study population and found that the use of MBS containing ingredients of both creatine and proteins increased the risk of TGCC significantly (OR = 2.55, 95% CI: 1.05–6.15).
I think most discussion and confusion revolves around what exactly they asked the participants, and the implications and meaning of the last quote. I feel shaky on what they asked, and what "MBS containing ingredients of both creatine and proteins" means (in particular, that quote makes me wonder if they looked at creatine and protein individually and there was a very low OR so they selected the combo to make a point? Otherwise, how can this be interpreted and why did they word it in such a seemingly strange way?) Why would they choose to not disclose the list of substances they asked about?
In our study, nearly 20% of cases with TGCC had used MBS, which was similar to the previous case series study (Chang et al, 2005)
This is also confusing to me in the context of creatine being a major risk factor because since 2001 (TABLE 10-18c), young male creatine usage has fluctuated between 16~22%. Is that a valid counterargument? (I understand that's just looking at 12th graders, but if 22% of 12th graders, avg age 18, used it 5-10 years before the study and creatine prevalence hadn't shifted much for a few years before that, it doesn't seem too unreasonable to use that data to speculate non-cause for the study).
I've made a long post with a bunch of questions, and I could come up with many more, but ultimately, I want to form an educated opinion on whether it's reasonable to suspect that creatine causes an increased risk of testicular cancer, given the variety of benefits it has been studied to have. Any thoughts?