Does Testosterone Injections Cause Prostate Cancer?
Testosterone injections do not cause prostate cancer, but they may unmask or accelerate the growth of pre-existing occult disease. The evidence consistently shows that testosterone replacement therapy (TRT) does not increase prostate cancer incidence above baseline population rates, though vigilant monitoring remains essential given the substantial prevalence of undetected cancer in hypogonadal men.
The Evidence Against Causation
Prospective studies demonstrate that testosterone therapy does not increase prostate cancer risk beyond general population rates. A comprehensive analysis of prospective TRT trials found only 5 cases of prostate cancer among 461 men (1.1%) followed for 6-36 months—a prevalence identical to the general population 1. This finding has been replicated across multiple study designs and patient populations 2.
The historical belief that testosterone causes prostate cancer stems from Huggins' 1940s work showing that castration causes prostate cancer regression 1. However, this demonstrates only that existing cancer is androgen-sensitive, not that testosterone initiates carcinogenesis 3. The "saturation model" explains this phenomenon: androgen receptors become saturated at relatively low testosterone levels, meaning additional testosterone beyond this threshold does not further stimulate prostate tissue 3, 4.
The Critical Caveat: Occult Cancer
The real concern is not causation but detection—14% of hypogonadal men with normal PSA and digital rectal examination harbor occult prostate cancer. In a study of 77 hypogonadal men who underwent prostate biopsy before TRT initiation, 11 men (14%) had undiagnosed cancer despite normal screening tests 1, 2. This substantial prevalence of hidden disease means testosterone may convert clinically silent cancer into detectable disease by promoting growth of pre-existing malignancy 1.
Case reports document prostate cancer diagnosis within months of TRT initiation 1, 5. However, attributing causality is problematic since over 200,000 men are diagnosed with prostate cancer annually in the United States, most detected by PSA elevation unrelated to testosterone therapy 1.
Mandatory Monitoring Protocol
Before initiating testosterone therapy, perform baseline digital rectal examination, PSA measurement, complete blood count, and liver function tests 2, 6. The FDA label explicitly states testosterone is contraindicated in men with known or suspected prostate cancer 6.
Follow-up schedule:
- Every 3-6 months during the first year 2
- Annually thereafter 2
- Monitor PSA, digital rectal examination, hemoglobin/hematocrit 2, 6
Thresholds for urologic referral and possible biopsy:
- PSA increase >1.0 ng/mL during first 6 months of treatment 2
- PSA increase >0.4 ng/mL per year after the first 6 months 2
- If threshold exceeded, repeat PSA in 3-6 months and perform biopsy if any further increase 2
Digital rectal examination proves particularly sensitive for detecting testosterone-associated cancers, often more so than PSA 5. In one series of 20 men diagnosed with prostate cancer after TRT initiation, median PSA at diagnosis was only 5.1 ng/mL (range 1.1-329.0), and digital rectal examination detected more cancers than PSA screening 5.
Safety in Treated Prostate Cancer
For men with treated prostate cancer, testosterone therapy appears safe with appropriate patient selection and monitoring. A review of 103 hypogonadal men treated with testosterone after radical prostatectomy showed only 4 recurrences over median 27.5 months follow-up 2. Multiple studies of TRT after definitive prostate cancer treatment report no increased recurrence rates 7, 3.
Even in men with untreated prostate cancer on active surveillance, limited evidence suggests TRT may be safe. In 13 symptomatic testosterone-deficient men receiving TRT while on active surveillance (median 2.5 years), no local progression or distant disease occurred, and 54% of follow-up biopsies showed no cancer 4.
Testosterone therapy remains absolutely contraindicated in men with active metastatic prostate cancer, where androgen deprivation is standard treatment 2.
Common Pitfalls
Physicians prescribing testosterone must monitor more vigilantly than those treating other conditions. In the case series by Morgentaler et al., patients followed by non-urologist physicians were monitored less frequently for prostate cancer than those followed by urologists, potentially delaying cancer detection 5.
Erythrocytosis occurs more frequently with intramuscular testosterone injections compared to transdermal preparations, requiring hemoglobin/hematocrit monitoring 1, 6. While no testosterone-associated thromboembolic events have been reported to date, appropriate measures (dosage reduction, therapeutic phlebotomy, or blood donation) should be instituted if erythrocytosis develops 1, 6.
Patients must understand the limitations of current evidence. No prospective study with sufficient power has definitively resolved the testosterone-prostate cancer relationship 8. Follow-up data beyond 36 months remain limited 1. The decision to use TRT involves weighing potential benefits against theoretical risks, particularly in men with cancer history 2.