Despite the well-proven benefits for testosterone replacement therapy (TRT), physicians are still fearful that testosterone may cause the progression of undiagnosed prostate cancer (PCa) or its development with advancing age. This is despite the evidence from several published reviews (Morgentaler and Roddam et al.), suggesting that the concept above is a “myth”. Similarly, Shabsigh et al. concluded from an extensive analysis of 44 studies that “none” demonstrated that TRT for hypogonadism increased prostate cancer risk or increased the Gleason grade of cancer detected in treated vs. untreated men.
Interestingly, the fears about TRT inducing PCa remain the main reason why many patients with hypogonadism remain untreated. According to a study by Gooren et al, it has been shown that about 68% of physicians are more concerned about the risks of TRT than the benefits (more so in Europe than elsewhere). The main reason quoted by 51% of the physicians surveyed was PCa. Furthermore, when asked if their readiness to prescribe testosterone to elderly men would increase if authoritative scientific evidence dismissed the fear that TRT would increase the risk of PCa and Benign Prostatic Hyperplasia (BPH), the response was overwhelmingly “yes” in 62% from Europe and 74% elsewhere.
In a very recent article by Feneley et al (J Sex Med 2012;9:2138-2149), an updated review of PCa safety from the UK Androgen Study was carried out to analyze the incidence of PCa during long-term TRT. The UK Androgen Study describes the long term outcomes for 1365 hypogonadal men who were treated with several different forms of treatment for at least 3 months and as long as 20 years. The men were aged 28-87 (mean 55), and they were pre-screened for PCa by digital rectal exam (DRE) and PSA at baseline and every 6 months. The abnormal findings on DRE or rising PSA were investigated by transrectal ultrasound with prostate biopsy. During the study, 14 cases of prostate cancer were diagnosed in men between 57 and 78 (mean 66) years of age, and 1-12 (mean 6.3) years of treatment. In most of these cases, the diagnosis was preceded by a clinically significant rise in PSA; however, any initial PSA change had no predictive relationship to the subsequent diagnosis of PCa. Furthermore, initiating TRT had no statistically significant effect on total PSA, free PSA, or free/total PSA ratio. Importantly, all new cases of PCa were clinically localized and suitable for potentially curative intent.
Despite the limitations that are inherent in an “observational clinical study” starting 20 years ago, the findings suggest that hypogonadal men can be treated safely and effectively without the increased risk for prostate cancer. The detection rate of PCa in this study was equivalent to that expected in the general population, implying that TRT does not cause prostate cancer. The majority of the hypogonadal men treated with TRT will have no adverse effects on the prostate; however, TRT may stimulate prostate cancer cells within a normal prostate gland to produce more PSA, improving the early detection of PCa in these patients. This is actually a clinical advantage (not a disadvantage) for patients undergoing TRT. Furthermore, there is a growing literature suggesting that normal testosterone levels can actually decrease the risk for high grade PCa.
In summary, physicians should not be deterred from initiating TRT due to theoretical fears and myths. The data from the study above (and others) demonstrates no increased risk for prostate cancer; however, close monitoring of the patients’ PSA is necessary as TRT may improve the early detection of PCa.