What is known
A pervasive concern with testosterone therapy is prostate disease.1,6 The fear that higher testosterone level will increase prostate cancer growth originated from a theory of testosterone-dependent prostate cancer growth that was seen in castrated men.6 This finding is not relevant to testosterone therapy in hypogonadal men; even low testosterone levels that are seen in men with testosterone deficiency are typically above the androgen saturation point (i.e. the level above which further increases in testosterone levels will not affect the prostate because it has already become saturated with androgens).7
Contrary to widespread belief, studies show that long-term testosterone therapy for up to 17 years does not increase prostate cancer incidence 8 (for more, see our previous editorial “Incidence of prostate cancer after testosterone therapy for up to 17 years”).
When prostate cancer does develop, it is men with low testosterone levels who develop higher grade (more advanced) prostate cancer.9-13 In fact, data suggest that low testosterone levels, especially low free testosterone, may be a marker for more aggressive prostate cancer.14-16 More recently, a study showed that low testosterone level is an independent risk factor for high-grade prostate cancer.17
The REDUCE trial found no significant association between testosterone levels and prostate cancer diagnosis; among men with the very highest levels of testosterone there was a trend towards a reduced number of prostate cancer diagnoses.18
A meta-analysis of 43 studies showed that testosterone therapy for hypogonadism does not increase prostate cancer risk or Gleason grade of cancer detected in testosterone treated vs untreated men.19 Another meta-analysis of 22 randomized controlled trials concluded that testosterone therapy does not promote prostate cancer development or progression.20
What this study adds
In the present study, the incidence and severity of prostate cancer, Gleason scores and tumor staging were assessed in prostate biopsies from hypogonadal men undergoing testosterone therapy, and compared with biopsies from eugonadal men and untreated hypogonadal men.1
The study was conducted between 2008 and 2013 and included 553 patients. Mean age at biopsy was 61 (range 46–81 years) and PSA 3.7 (range 0.28–7.23 mg/mL). The incidence and severity of prostate cancer was assessed via biopsy in three patient groups presenting at a urology clinic:
(a) 42 hypogonadal men (testosterone level <12.1 ng/dL or <350 ng/dL) receiving testosterone therapy.
(b) 162 untreated hypogonadal men, with a median pretreatment total testosterone level of 7.1 nmol/L or 205 ng/dL (range 3.3 - 11.7 nmol/L or 95 – 337 ng/dL).
(c) 349 eugonadal men.
Biopsies were performed when indicated and following patient consent, according to the European Association of Urology (EAU) guidelines.21
As illustrated in table 1, pathological analysis of prostate biopsies examining the incidence and severity of prostate cancer revealed that:
17% (7 patients) of treated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 71% and >6 in 29% of men, a predominant score of 3 in all men (100%) and tumour staging of II in 86% men;
52% (84 patients) of untreated hypogonadal men had a positive biopsy, a Gleason score of ≤6 in 41% and >6 in 60% men, a predominant score of 3 (77%) and tumour staging of II (42%) or III (41%);
38% (132 patients) of eugonadal men had a positive biopsy, a Gleason score of ≤6 in 42% and >6 in 58% of men, a predominant score of 3 (83%) and tumour staging of II (45%) or III (48%).