Relationship Between Testosterone and Prostate Cancer
Current evidence does not support a causal link between testosterone therapy and the development of prostate cancer, though caution is warranted in men with a history of prostate cancer due to limited long-term safety data. 1
Evidence on Testosterone and Prostate Cancer Risk
General Population
- The American Urological Association (AUA) provides a strong recommendation (Evidence Level: Grade B) that clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer 1
- The historical prohibition against testosterone therapy in men with prostate cancer was based on an outdated model that assumed prostate cancer sensitivity to testosterone extended throughout all concentration ranges 2
Saturation Model
The current understanding follows a "saturation model" which suggests:
- Prostate cancer growth becomes androgen-indifferent at higher testosterone concentrations 2
- This explains why serum testosterone appears unrelated to prostate cancer risk in the general population 2
- The androgen receptor has a finite capacity to bind testosterone, becoming saturated at relatively low testosterone levels 2
Testosterone Therapy After Prostate Cancer Treatment
Post-Radical Prostatectomy
- Testosterone therapy can be considered in men who have undergone radical prostatectomy with favorable pathology (negative margins, negative seminal vesicles, negative lymph nodes) and undetectable PSA 1
- In a study of 103 hypogonadal men receiving testosterone after prostatectomy, only 4 cancer recurrences were observed compared to 8 recurrences in the 49-patient reference group not receiving testosterone 3
Post-Radiation Therapy
- Studies show that men treated with radiation therapy (with or without prior androgen deprivation therapy) generally do not experience recurrence or progression of prostate cancer when given testosterone therapy 1
- These patients typically experience either steady PSA decline to <0.1 ng/mL or non-significant changes in PSA 1
Active Surveillance
- Limited data exists on testosterone therapy in men on active surveillance 1
- Available evidence suggests patients with or without high-grade prostatic intraepithelial neoplasia on testosterone therapy did not experience significant PSA increases or subsequent cancer diagnosis compared to men not receiving testosterone 1
Monitoring Recommendations
PSA Monitoring
- PSA should be measured in men over 40 years before starting testosterone therapy to exclude occult prostate cancer 1, 4
- Prostate cancer patients on testosterone therapy should have PSA monitored on the same schedule as men without testosterone deficiency, though clinicians may choose to increase monitoring frequency 1
- Consider urologic referral if PSA increases by more than 1.0 ng/mL during the first six months or more than 0.4 ng/mL per year thereafter 4
Other Monitoring
- Hemoglobin/hematocrit should be monitored due to testosterone's effect on erythropoiesis 4, 5
- Intervention is required if hematocrit exceeds 54% (dose reduction or temporary discontinuation) 4
Cautions and Contraindications
- The AUA recommends that testosterone therapy in men with in-situ prostate cancer on active surveillance or previously treated prostate cancer should be approached with caution (Moderate Recommendation; Evidence Level: Grade C) 1
- Testosterone therapy in men with locally advanced or metastatic prostate cancer remains poorly understood and should ideally be performed under research settings 1
- The FDA warns that geriatric patients treated with androgens may be at increased risk of developing prostatic hypertrophy and prostatic carcinoma, though conclusive evidence is lacking 5
Clinical Concerns
- A retrospective study identified 20 men diagnosed with prostate cancer after initiating testosterone therapy, with 55% detected within 2 years of starting treatment 6
- Digital rectal examination was generally more sensitive than PSA in detecting these cancers 6
- Testosterone therapy may increase PSA in some men with a history of prostate cancer, but this doesn't necessarily indicate cancer recurrence 3, 2
Conclusion
While the traditional prohibition against testosterone therapy in men with prostate cancer history is being reconsidered based on newer evidence, patients should be informed that there is inadequate evidence to fully quantify the risk-benefit ratio of testosterone therapy in this population. Careful patient selection, appropriate monitoring, and shared decision-making are essential when considering testosterone therapy in men with a history of prostate cancer.