Tag Archive for: testosterone


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




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



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


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.


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).


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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Article of the week: Free testosterone levels in PCa reclassification

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance

Ignacio F. San Francisco, Pablo A. Rojas, William C. DeWolf* and Abraham Morgentaler*

Departamento de Urología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile and *Division of Urological Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

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To determine whether total testosterone and free testosterone levels predict disease reclassification in a cohort of men with prostate cancer (PCa) on active surveillance (AS).


Total testosterone and free testosterone concentrations were determined at the time the men began the AS protocol. Statistical analysis was performed using Student’s t-test and a chi-squared test to compare groups. Odds ratios (ORs) with 95% confidence intervals (CIs) were obtained using univariate logistic regression. Receiver–operator characteristic curves were generated to determine the investigated testosterone thresholds. Kaplan–Meier curves were used to estimate time to disease reclassification. A Cox proportional hazard regression model was used for multivariate analysis. You can learn about testosterone here and so much more for your health.


A total of 154 men were included in the AS cohort, of whom 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone levels than those who were not reclassified (0.75 vs 1.02 ng/dL, P = 0.03). Men with free testosterone levels <0.45 ng/dL had a higher rate of disease reclassification than patients with free testosterone levels ≥0.45 (P = 0.032). Free testosterone levels <0.45 ng/dL were associated with a several-fold increase in the risk of disease reclassification (OR 4.3, 95% CI 1.25–14.73). Multivariate analysis showed that free testosterone and family history of PCa were independent predictors of disease reclassification.


Free testosterone levels were lower in men with PCa who had reclassification during AS. Men with moderately severe reductions in free testosterone level are at increased risk of disease reclassification.

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Editorial: The importance of knowing testosterone levels in patients with prostate cancer

The paper by San Francisco et al. [1] in this issue of BJUI, reviews 154 patients with prostate cancer who were included in an active surveillance cohort. In all, 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone than those who were not reclassified. They concluded that on multivariate analysis, free testosterone and a family history of prostate cancer were independent predictors of disease reclassification. The authors acknowledge that this was a retrospective study of small size and the data was missing in some of the men, sex hormone-binding globulin (SHBG), luteinizing hormone and oestradiol were not measured. Nevertheless, this review adds to the increasing evidence that it is important to measure testosterone levels in men with prostate cancer.

Previous studies have indicated that a low testosterone level before treatment for prostate cancer is an independent predictor of a more aggressive high-grade cancer [2]. In addition to this, there appears to be an increased likelihood of extraprostatic disease at the time of diagnosis [3] and an unfavourable response to treatment [4].

Garcia-Cruz et al. [5] in 2012 reported that low testosterone bioavailability is related to a positive prostate cancer diagnosis in patients submitted for prostate biopsy. In a further study, he showed that low testosterone levels were related to poor prognosis factors in men with prostate cancer prior to treatment. Testosterone was inversely related to prostate cancer bilaterally and percentage of tumour in the biopsy. Higher testosterone levels were found in patients allocated to the low-risk progression group. In the multivariate analysis, older age and lower testosterone levels were related to a higher D’Amico risk of progression [5]. The researchers went on to show that higher SHBG and lower bioavailable testosterone are related to prostate cancer detection on biopsy. The study was a prospective analysis of 279 patients referred for prostate biopsy. Low bioavailable testosterone and high SHBG levels were related to a 4.9- and 3.2-fold increased risk of detection of prostate cancer on prostate biopsy taken due to an abnormal PSA result or an abnormal DRE [6].

Free testosterone accounts for about 1–2% of total testosterone and hence most circulating testosterone is bound to SHBG and as such, is inactive. Yamamoto et al. [7] had previously shown that men with a low free testosterone (<1.5 ng/dL) had an increased risk of a high Gleason score (>8) compared with men with higher free testosterone (8% vs 2%; P = 0.04). Additionally, a free testosterone level of <1.5 ng/dL was associated with increased risk of biochemical recurrence of tumour.

Morgentaler et al. [8] have been turning conventional wisdom upside down. They report on 13 symptomatic testosterone deficient men who also had untreated prostate cancer. The men received testosterone therapy while undergoing active surveillance for a median of 2.5 years. None of the men had aggressive or advanced prostate cancer and they were rigorously followed up. Despite effective treatment, neither the PSA level nor prostate volume showed any change. Follow-up biopsies were taken in all of the men at yearly intervals and none developed cancer progression.

It is intriguing to think that the decline in testosterone with age and comorbidities may contribute to tumorigenesis in the prostate. Clearly this study needs to be replicated with much larger numbers. But it seems reasonable to suggest that we ought to know about the hormonal environment existing in our patients with prostate cancer. This will of course, raise the even more controversial area of what to do about men with symptomatic hypogonadism with treated and untreated prostate cancer. There is limited data available on this issue.

Before considering testosterone therapy, the first step should be intensive lifestyle intervention; this is not only known to improve cancer survival, but raises total and free testosterone. Weight loss inhibits aromatase, and other complex cytokines, this reduces the suppression of the pituitary gonadal axis and conversion of testosterone to oestrogen, raising testosterone levels.

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Michael Kirby*,†
*The Prostate Centre, London, and Institute of Diabetes for Older People (IDOP), Beds & Herts Postgraduate Medical School, Puckeridge Bury Campus, Luton, UK


  1. San Francisco I, Rojas P, Dewolf W, Morgentaler A. Low free testosterone predicts disease reclassification in men with prostate cancer undergoing active surveillance. BJU Int 2014; 114: 229–235
  2. Massengill JC, Sun L, Moul JW et al. Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. J Urol 2003; 169: 1670–1675
  3. Chen SS, Chen KK, Lin AT, Chang YH, Wu HH, Chang LS. The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis. BJU Int 2002; 89: 710–713
  4. Ribeiro M, Ruff P, Falkson G. Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer. Am J Clin Oncol 1997; 20: 605–608
  5. Garcia-Cruz E, Piqueras M, Huguet J et al. Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment. BJU Int 2012; 110: E541–546
  6. Garcia-Cruz E, Carrión Puig A, Garcia-Larrosa A et al. Higher sex hormone-binding globulin and lower bioavailable testosterone. Scand J Urol 2013; 47: 282–289
  7. Yamamoto S, Yonese J, Kawakame S et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007; 52: 696–701
  8. Morgentaler A, Liphultz LI, Bennett R, Sweeney M, Avila D Jr, Khera M. Testosterone therapy in men with untreated prostate cancer. J Urol 2011; 185: 1256–1260
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