Re: Cancer and Low Testosterone Levels

The relationship between testosterone concentrations and the risk of cancer, particularly prostate cancer in men, is of great interest right now, and there are conflicting reports in the scientific literature. The potential relationship is of great interest for two reasons:

1. The involvement of the androgen receptor (a protein that causes cellular responses to testosterone) in the development of prostate cancer is well established, but the ability of drugs that block this receptor to treat prostate cancer is not as clear, nor is the relationship between testosterone levels and androgen receptor activity.

2. Many aging men are interested in receiving testosterone replacement therapy to combat age-related declines in testosterone and the associated physiological effects (e.g. decreased bone density, decreased sex drive), but are concerned that such therapy may put them at risk for prostate cancer.

The available publications give conflicting reports for several reasons. For one, testosterone in the bloodstream is mostly bound to proteins, but it's the free (unbound) hormone that is active. Some studies measure both total and free testosterone, some only total, and some measure total but use a formula to estimate free testosterone based on other characteristics. As you might imagine, these different methods can yield different results. A second problem is that each report studies a different group of people, and some do a better job than others of amassing a large population more likely to show reliable trends. Finally, different studies may examine different outcomes, such as prostate cancer versus other types, the incidence of any kind of prostate cancer, or advanced versus early stage prostate cancer.

I couldn't find a good overall summary of what's known, either on a web site or in a scientific publication, so below I've listed some fairly recent work with a short summary of what they've found to give you a flavor for what's being done. Beside each is a PMID number, which can be entered at http://www.ncbi.nlm.nih.gov/pubmed/ to give you the full citation and abstract if you want to know more.

19124495 Sieri et al. report that total and free testosterone concentration both correlate with a higher incidence of breast cancer in women (this is one of the few studies NOT looking at prostate cancer)

19220251 Morote et al. find no relationship between total or free testosterone and prostate cancer incidence

17562541 Wiren et al. similar result to previous listing

16434592 Severi et al. found a weakly protective effect of increased testosterone levels, that is, men with higher levels had a lower incidence of aggressive prostate cancer (but the same risk of prostate cancer overall)

16172240 Parsons et al. show that high free testosterone (but not total testosterone) correlates with increased risk of prostate cancer

17911176 Laughlin et al. studied mortality rates in relation to testosterone levels and found an increased risk of cardiovascular and respiratory death in men with low testosterone, but no correlation with cancer death rate

This one hasn't been published yet, but Yassin et al. presented at last year's meeting of the Endocrine Society that men who received testosterone replacement therapy did not have an increased risk of prostate cancer