Testosterone Replacement Therapy and the Risk of Prostate Cancer. Is There a Link?

A. Barqawi; E. D. Crawford


Int J Impot Res. 2006;18(4):323-328. 

In This Article

Suggested Monitoring Guidelines

A digital rectal examination (DRE) and PSA levels should be used to exclude prostate cancer before initiating TRT in hypogonadal men. The role of DRE in detecting early, clinically significant, prostate cancer is substantially hampered by the high false negative rate, which, largely reflects in contradictory reports for its value as a screening tool.[32,33] In a recent large review study, DRE findings did not correlate with biopsy findings and pathological stage.[34] However, DRE is still mandatory in all men with PSA >2.5 ng/dl and may play a role in target biopsy of the prostate. The use of validated nomograms[35] (based on age, PSA, %fPSA, and DRE) is recommended when in doubts, to aid in the decision for recommending biopsy of the prostate before TRT initiation in some patients. DRE and PSA should be performed every 3 months in the first year and then semiannually.[34] It is important to note that, such recommended regimen for screening, is arbitrary, and not supported by published data. However, in our opinion it represents a sensible clinical practice that can be applied at our current knowledge. PSA velocity (rate of change in PSA level over time) can be utilized to monitor the dynamic risk of prostate cancer overtime and the need for prostate biopsy.[36] A suggested PSA doubling time of <12 months in men with initial PSA levels of >1 ng/dl, may indicate exclusion of prostate cancer by extended biopsy.[36]

Little evidence exists on the safety of TRT initiation after treatment for primary prostate cancer. Agarwal et al.[37] treated 10 hypogonadal men, treated for organ-confined prostate cancer, with TRT for a median of 18 months. They reported no PSA recurrence in all men with associated significant symptomatic improvement in quality of life indices. However, there are no documented large and long-term studies proving that the risk of recurrence is not affected by TRT in men treated with definitive therapy. A known risk of recurrence or biochemical failure after radical prostatectomy is estimated to be 10-20% within 15 years indicating that the possibility of micrometastasis at the time of diagnosis is real and substantial.[38] In our opinion, until the true association between TRT and the risk of prostate cancer is established, the recommendations for TRT after radical prostatectomy should be contraindicated in the mainstream urological practice and probably only practiced under strict research protocols.

After TRT is initiated, a rigorous follow-up should be employed, including the monitoring of T levels. According to the recent EAU, ISA recommendations, symptomatic men with total T levels of <231 ng/dl or free T of <52 pg/ml should be offered TRT.[39] Monitoring of treatment should aim at maintaining total T levels between 346 ng/dl (free T>72 pg/ml) and 500 ng/dl, by adjusting route and dosage of TRT regimens. It is theoretically inadvisable to recommend higher doses of TRT and the dose should reflect an improvement in LOH symptoms, with the lowest possible dosage. DHT levels are not routinely recommended to be monitored during TRT.

Other adverse events linked to TRT but unrelated to prostate cancer risk include the aggravation of Lower urinary tract symptoms (LUTS), that may occur in older men with existing benign prostatic hyperplasia-related symptoms and should be monitored on regular intervals in these men. Other potential adverse events in men treated with TRT for prolonged periods is erythrocytosis and sleep apnea. Hemoglobin (HCT), should be monitored semiannually and baseline determination of sleep apnea is recommended and should be monitored at each visit.


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