madman
Super Moderator
ABSTRACT
With prostate cancer not observed in eunuchs and total androgen suppression by castration an effective first-line treatment for advanced prostate cancer, the dramatic regression seen in tumour symptoms after castration, lead to the theory that high levels of circulating androgens were a risk factor for prostate cancer. This theory however, ignored the effects testosterone variations within a physiologic range could have on early tumour events and since the early 2000s, clinical evidence discounting testosterone as a linear mechanistic cause of prostate cancer growth mounted, with alternative mechanistic hypotheses such as the saturation model being proposed. Together with a growing understanding of the negative health effects and decreased quality of life in men with testosterone deficiency or hypogonadism, a paradigm shift away from testosterone as a prostate cancer inducer occurred allowing clinicians to use testosterone therapy as potential treatment for men with difficult and symptomatic hypogonadism that had been previously treated for prostate cancer. In this review we contextualise the idea of testosterone as a risk factor for prostate cancer inducement and compile the most current literature with regards to the influence of testosterone and testosterone therapy in prostate cancer.
Conclusion
Our understanding of testosterone influence in prostate cancer has come a long way since higher levels were proposed to be a causal risk. Mounting evidence has shown the relationship to be complex and new ideas such as bipolar androgen treatment have even been proposed to control prostate cancer through normalisation of testosterone concentrations.
Although not statically significant, meta-analysis of randomised placebo-controlled trials, investigating the use of testosterone therapy and its association with prostate cancer, have reported a reduction in prostate cancer risk [52,53]. Observational studies have also shown the risk to be low for men previously treated with radical prostatectomy or radiotherapy. And, although for men with untreated prostate cancer fewer data are available, reports also suggest that testosterone therapy is safe in men on active surveillance.
Congruently, the positive effects of testosterone therapy in the overall quality of life of hypogonadal patients have been extensively described [3] and, to date, many reports have refuted other health concerns such as increased risk of disease or venous thromboembolism.
The data here from a wide range of investigations and analyses thus show the negative view of testosterone therapy as a risk factor for prostate cancer to be ill funded. The need for long-term large-scale placebo controlled trials to definitively assess the safety of testosterone therapy is still needed; particularly to fully assess its impact on prostate cancer patients untreated for the condition. Indeed, more research is needed in order to truly understand the complex relationship of testosterone and prostate cancer. However, with preliminary research suggesting that testosterone treatment may be useful to help manage the disease it is the time that its negative association with increased prostate cancer risk stops impacting on prospective treatment of hypogonadism men and is recognised, for what it is, an historical misunderstanding.
With prostate cancer not observed in eunuchs and total androgen suppression by castration an effective first-line treatment for advanced prostate cancer, the dramatic regression seen in tumour symptoms after castration, lead to the theory that high levels of circulating androgens were a risk factor for prostate cancer. This theory however, ignored the effects testosterone variations within a physiologic range could have on early tumour events and since the early 2000s, clinical evidence discounting testosterone as a linear mechanistic cause of prostate cancer growth mounted, with alternative mechanistic hypotheses such as the saturation model being proposed. Together with a growing understanding of the negative health effects and decreased quality of life in men with testosterone deficiency or hypogonadism, a paradigm shift away from testosterone as a prostate cancer inducer occurred allowing clinicians to use testosterone therapy as potential treatment for men with difficult and symptomatic hypogonadism that had been previously treated for prostate cancer. In this review we contextualise the idea of testosterone as a risk factor for prostate cancer inducement and compile the most current literature with regards to the influence of testosterone and testosterone therapy in prostate cancer.
Conclusion
Our understanding of testosterone influence in prostate cancer has come a long way since higher levels were proposed to be a causal risk. Mounting evidence has shown the relationship to be complex and new ideas such as bipolar androgen treatment have even been proposed to control prostate cancer through normalisation of testosterone concentrations.
Although not statically significant, meta-analysis of randomised placebo-controlled trials, investigating the use of testosterone therapy and its association with prostate cancer, have reported a reduction in prostate cancer risk [52,53]. Observational studies have also shown the risk to be low for men previously treated with radical prostatectomy or radiotherapy. And, although for men with untreated prostate cancer fewer data are available, reports also suggest that testosterone therapy is safe in men on active surveillance.
Congruently, the positive effects of testosterone therapy in the overall quality of life of hypogonadal patients have been extensively described [3] and, to date, many reports have refuted other health concerns such as increased risk of disease or venous thromboembolism.
The data here from a wide range of investigations and analyses thus show the negative view of testosterone therapy as a risk factor for prostate cancer to be ill funded. The need for long-term large-scale placebo controlled trials to definitively assess the safety of testosterone therapy is still needed; particularly to fully assess its impact on prostate cancer patients untreated for the condition. Indeed, more research is needed in order to truly understand the complex relationship of testosterone and prostate cancer. However, with preliminary research suggesting that testosterone treatment may be useful to help manage the disease it is the time that its negative association with increased prostate cancer risk stops impacting on prospective treatment of hypogonadism men and is recognised, for what it is, an historical misunderstanding.
