Many men, after they have had a radical prostatectomy, find that their testosterone levels are low and are desirous of supplementing their testosterone. (This low level of testosterone is not a result of the surgery). One way of supplementing androgens is by transdermal testosterone-replacement therapy (TRT), but TRT also has the undesirable effect of increasing prostate-specific antigen (PSA) levels.

In research performed by Alexander W. Pastuszak, MD, from Scott Department of Urology at the Baylor College of Medicine in Houston, it was found that despite the increase in PSA levels the use of TRT did not appear to increase biochemical recurrence rates during a follow-up period of a median of 27.5 months for treated men.

One can only describe these findings as a mixed result. According to Dr. Pastuszak the lack of a higher biochemical recurrence rate in the treatment group, is “interesting and potentially significant.”

In reality there is very limited research on TRT in men with prostate cancer. According to the study authors fewer than 600 men with prostate cancer have been treated with TRT (in a variety of ways) and studied.

This retrospective study had a sample of 153 men (small sample) who had undergone a radical prostatectomy — 103 who were hypogonadal and were treated with TRT and 50 who were not hypogonadal.

The study authors cautioned that it is “premature to postulate that TRT in men with a history of prostate cancer may be protective”.

Even after this study the use of TRT in prostate cancer remains controversial. Earlier research has established that prostate cancer is androgen-dependent and that adding androgens can fuel the cancer. Additionally, there were studies in the 1960s and 1970s that found that TRT led to “tumor growth and/or recurrence in patients with metastatic or advanced prostate cancer.”

According to Dr. Pastuszak, “The landmark study that initially linked testosterone and prostate cancer was done in 3 patients with metastatic prostate cancer in whom castration resulted in regression of the prostate cancer.”
Additional research conducted in the past 10 years has shown that TRT is not associated with prostate cancer recurrence or progression, according to the authors.

The authors went on to report that in “several studies” of men treated with prostatectomy — all involving fewer than 60 men — TRT did not increase the risk for biochemical recurrence or progression. This most recent study supports this finding.
In men with low levels of testosterone the health benefits of TRT have become “more firmly established” and include improved vitality, sexual desire, bone health, and cardiovascular function, the study authors report.

According to Wayne J.G. Hellstrom, MD, chief of the section of andrology in the Department of Urology at Tulane University School of Medicine in New Orleans, Louisiana clinicians who give testosterone to men who have been treated for prostate cancer need to closely monitor these patients despite the results of this and other related studies.

Both Drs. Hellstrom and Pastuszak use a similar schedule when administering TRT to men who have been surgically treated for prostate cancer. They waited 1 year before starting TRT and then follow PSA values every 3 to 4 months for the first year. If no significant change occurs, they move to every 6 months for a year, then annually.

However, The Endocrine Society’s Clinical Guidelines on men with androgen-deficiency syndromes specifically recommend against testosterone therapy in men with breast or prostate cancer.

In Dr. Pastuszak’s study all men who received TRT had at least 1 PSA level that was undetectable after radical prostatectomy. In the TRT group, 26 men had high-risk and 77 had low/intermediate (non-high)-risk prostate cancer. In the reference group, 15 men had high-risk and 35 had nonhigh-risk prostate cancer.

In the TRT group, there was a small but statistically significant increase in PSA in the high-risk and nonhigh-risk groups beginning 18 to 24 months after TRT initiation. This suggests that “an overall trend toward increasing PSA does occur in men on TRT.”

In contrast, there was no overall significant increase in PSA in the reference group.

Men in the TRT group had significant increases in serum testosterone levels at almost all follow-up time points, which extended out to 36 months.
Biochemical recurrence, defined as consecutive increasing PSA levels and patient referral for salvage radiation therapy, occurred in 4 patients in the TRT group and 8 in the reference group, but the recurrence rates were similar and non-significant. Notably, all recurrences in the TRT and reference groups were in high-risk patients.

Malecare’s overall concern about using TRT in men who have been treated with prostate cancer remains despite this study. This study was too small and our biggest concern is that the follow-up time of only 36 months is not long enough. We are hopeful that TRT can be made available to treated men, but only after a more robust and long term study.

J. Urol. 2013;190:639-644.

Joel T Nowak, M.A., M.S.W.