Testosterone Replacement Therapy and the Risk of Prostate Cancer. Is There a Link?

A. Barqawi; E. D. Crawford


Int J Impot Res. 2006;18(4):323-328. 

In This Article

Epidemiological Evidence of a Correlation Between Testosterone and Prostate Cancer

Several epidemiological studies have reported that low testosterone levels have an adverse effect on men with newly diagnosed prostate cancer. Schatzl et al.[19] suggested an enhanced malignant potential associated with low serum testosterone, describing higher AR density and a more aggressive tumor. Massengill et al.[20] reported a significant association between low serum testosterone and an increase in the likelihood of extraprostatic disease in men with localized disease.[20] Imamoto et al.[21] recently reported that low pretreatment serum testosterone levels had a significant predictive value for higher stage prostate cancer in 82 patients with clinically localized prostate cancer. Some controlled studies have reported that, compared with men with normal testosterone levels, men with low testosterone have a significantly shorter interval to disease progression and a worse prognosis after hormonal manipulation in metastatic disease.[22] On the other hand, the effect on downstream testosterone metabolism of TRT increasing low levels of testosterone to levels that are above normal may contribute to the effect of TRT on prostate cancer risk. Shaneyfelt et al.[23] conducted a meta-analysis that found a two-fold increase in the risk of prostate cancer in men with testosterone levels in the upper quartile of the population. Conversely, Chen et al.[24] found no correlation between the incidence of prostate cancer and testosterone levels in a sub-analysis of 300 men from the Carotene and Retinol Efficacy Trial. In a study involving 486 men with clinically localized prostate cancer treated by radiation, Zagars et al.[25] reported a markedly higher metastatic rate in men with a testosterone level ≥500 ng/dl. The study by the Finnprostate Group, however, found no correlation between pretreatment testosterone levels and metastatic prostate cancer.[26] These seemingly conflicting reports of the effect of serum testosterone levels on the risk of clinical progression of prostate cancer suggest a U-shaped relationship between prostate cancer and androgens, in which extremes in testosterone levels may adversely affect the risk of prostate cancer.

Whether or not men on longterm TRT have an increased incidence of prostate cancer, several prospective studies have reported that these men have a low frequency of disease that is comparable to the general population.[4,27] Nevertheless, it is important to note that a causal relationship cannot be established based on observational epidemiological studies, and these correlations should be viewed with caution.


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