Is Low Testosterone a Prostate Cancer Risk?

According to some studies it may be, including a paper just recently published in the Korean Journal of Urology (1). It concerns an evaluation of 568 patients that underwent prostate biopsy in South Korea due to elevated PSA levels (> 4 ng/mL). Using additional laboratory blood work, the researchers separated these men into two groups. One group had testosterone levels below 385 ng/dL (average 286 ng/dL), and the other levels equal to or above 385 ng/dL (average 520 ng/dL). The researchers then reviewed patient outcomes to identify 194 cases of prostate cancer in the men. The prominence of cancer was significantly higher in the first group, suggesting that low hormone levels may be a risk factor for the disease.

History

The role of testosterone in prostate cancer has interested scientists for decades. Prostate cancer was first identified as androgen-dependent back in 1941 (2). That year, androgen depravation was shown to shrink prostate tumor size, while the administration of testosterone to men with the disease caused tumors to grow. Since then, many additional clinical studies have established associations between testosterone and the disease (3). For example, long-term depletion of testosterone has even been consistently shown to protect healthy men against prostate cancer. Similar outcomes have been reported with studies using the dihydrotestosterone (DHT) inhibitors finasteride and dutasteride.

That some relationship exists between testosterone and prostate cancer is clear. How far this association goes, however, remains the subject of much confusion. For example, several recent studies have failed to find any association between the testosterone level and disease risk in men. This includes one large epidemiological review of 3,886 men with prostate cancer and 6,438 men without (4). In other words, these studies are finding that men with higher testosterone levels don’t seem to get the disease more often than men with more modest androgen concentrations. This finding is important, given the increased prominence of older men undergoing hormone replacement therapy and elevating their testosterone levels with injections (cypionate, enanthate) and transdermal gels (Androgel, Testim, Axiron, Fortesta).

Discussion

The present study has certain limitations, the least of which is not a small population size. Very often, much larger numbers are required to draw out strong statistical associations. The paper also doesn’t go far enough into differentiating correlation from causality. For example, the authors concede that low testosterone levels may be the result of tumors suppressing the hypothalamic-pituitary-testicular axis. Therefore, low testosterone levels might be an indicator of the disease, not necessarily a cause. It is difficult to draw conclusions at this time. The relationship between low testosterone levels and prostate cancer risk remains unclear, though more research is clearly needed.

References:
(1) Is a decreased serum testosterone level a risk factor for prostate cancer? A cohort study of Korean men. Bo Sung Shin, Eu Chang Hwang et al. Korean Journal of Urology (2010; 51:819-823).
(2) Studies on prostatic cancer: I. The effect f castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J Urol 2002; 168:9-12.
(3) Significance of serum testosterone from prostate-specific antigen (PSA_ elevation and prediction of prostate cancer in patients with PSA above 10 ng/ml. Jin Mo Koo, Bong Suk Shim. Korean Journal of Urology (2010;51:831-835).
(4) Endogenous Hormones and Prostate Cancer Collaborative Group. Roddam AW, Allen NE et al. J Natl Cancer Inst 2008; 100:170-83.