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Editorial: Malignant medication? Testosterone and cancer

Testosterone therapy (TTh) in men with hypogonadism is becoming more commonplace among urologists, endocrinologists and even primary practitioners. While the definition of hypogonadism remains a moving target, the literature reflects very clear benefits of TTh in appropriately selected patients. As with any drug, the adverse effect profile helps to dictate the risk:benefit ratio and, over the past several years, numerous, primarily retrospective, analyses have provided mixed insights into the impact of TTh on cardiovascular disease and cancer, specifically prostate cancer.

Eisenberg et al. [1] take a step back from the focus on prostate cancer and evaluate the impact of TTh on general cancer incidence in a cohort of men treated in a single, large-volume andrology practice over 20 years. The authors found no difference in either overall cancer incidence or in the prostate cancer incidence in men on TTh in comparison with men not on TTh. This finding is significant as it supports the hypothesis that testosterone does not harmfully affect either hormonally responsive (prostate cancer) or non-hormonally responsive malignancies. Interestingly, the authors also observe a lower rate of all cancers in men on testosterone therapy. While not statistically significant, this finding is consistent with that of at least one other study focused on prostate cancer, in which men with high-risk prostate cancer receiving exogenous testosterone had a lower recurrence rate than a matched control group [2]. If borne out in future studies, a protective relationship between TTh and cancer would indeed reflect a novel benefit of treatment.

Nevertheless, at this time the jury remains out on a definitive assessment of the effects of TTh on both cancer as well as cardiovascular disease, and will probably continue to do so until controlled, prospective studies are completed. Numerous, mostly retrospective studies have examined the effects of endogenous testosterone and of the administration of exogenous testosterone, primarily on prostate cancer. While the details of these studies are beyond the scope of the present editorial, their findings have varied with regard to whether testosterone does or does not have effects on cancer incidence, biopsy findings, grade, recurrence rates and margin status, preventing a clear perspective on the effects of testosterone on cancer. Similarly, studies evaluating the impact of TTh on cardiovascular disease have also widely varied in their conclusions [3, 4]. Several recent large retrospective studies have found a detrimental relationship between TTh and cardiovascular disease in specific male populations, but have come under withering criticism from the community, with significant doubts cast regarding the veracity of their findings [5, 6].

The growing popularity of TTh has subjected it to a level of scrutiny applied to few other medications, resulting in a slew of peer-reviewed publications of varying quality and conclusions. In the effort to safeguard patients, investigators have hurriedly carried out retrospective data evaluation, which, by design, limits compensation for confounding factors and unfortunately results in an overall murky understanding of long-term adverse events related to TTh. Nevertheless, the clinical benefits of TTh are clear, and many patients are satisfied with the results of treatment. While physicians should remain the stewards of patient care, informed consent and a patient’s acceptance of both the known as well as the unknown risks of testosterone treatment should continue to be an integral part of the initiation and continuation of TTh, until additional high-quality data from clinical trials become available in the coming years.

Alexander W. Pastuszak
Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

 

References

 

1 Eisenberg ML, Li S, Betts P et al. Testosterone therapy and cancer risk. BJU Int 2015; 115: 317–21

 

2 Pastuszak AW, Pearlman AM, Lai WS et al. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol 2013; 190: 639–44

 

3 Basaria S, Coviello AD, Travison TG et al. Adverse events associated with testosterone administration. NEnglJMed2010; 363: 109–22

 

4 Shores MM, Smith NL, Forsberg CW et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Meta2012; 97: 2050–8

 

 

6 Finkle WD, Greenland S, Ridgeway GK et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 2014; 9: e85805

 

Video: Does TT status modify a man’s risk of cancer?

Testosterone Therapy and Cancer Risk

Michael L. Eisenberg*, Shufeng Li*, Paul Betts§, Danielle Herder, Dolores J. Lamb¶ and Larry I. Lipshultz

 

Departments of *Urology, Obstetrics/Gynecology and Dermatology, Stanford University School of Medicine, Stanford, CA§Cancer Epidemiology and Surveillance Branch, Texas Cancer Registry, Texas Department of State Health Services, Austin, TX, and Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

 

OBJECTIVE

To determine if testosterone therapy (TT) status modifies a man’s risk of cancer.

PATIENTS AND METHODS

The Urology clinic hormone database was queried for all men with a serum testosterone level and charts examined to determine TT status. Patient records were linked to the Texas Cancer Registry to determine the incidence of cancer. Men accrued time at risk from the date of initiating TT or the first office visit for men not on TT. Standardised incidence rates and time to event analysis were performed.

RESULTS

In all, 247 men were on TT and 211 did not use testosterone. In all, 47 men developed cancer, 27 (12.8%) were not on TT and 20 (8.1%) on TT. There was no significant difference in the risk of cancer incidence based on TT (hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.57–1.9; P = 1.8). There was no difference in prostate cancer risk based on TT status (HR 1.2, 95% CI 0.54–2.50).

CONCLUSION

There was no change in cancer risk overall, or prostate cancer risk specifically, for men aged >40 years using long-term TT.

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