Dr. Weeks’ Comment: Abraham Morgentaler MD has been studying testosterone all his professional life and his minority opinion, that testosterone is not universally dangerous for men with prostate cancer, is shocking and compelling. I have posted and commented on many of his prior studies here and here and here. But now I want to share two excellent YouTube videos for people with prostate cancer to view for their edification.
To learn how the media frenzy was wrong to tell you that heart disease is made worse by testosterone, watch THIS (short) and THIS. (more detailed)
and read the abstract to this article
Clinicians are wise to remember the words of Galileo Galilei:
“In questions of science, the authority of a thousand is not worth the humble reasoning of a single individual.”
Today, more scientists are thinking clearly on this topic and some articles are summarized below.
J Urol. 2011 Apr;185(4):1256-60. doi: 10.1016/j.juro.2010.11.084. Epub 2011 Feb 22.
Testosterone therapy in men with untreated prostate cancer.
Morgentaler A1, Lipshultz LI, Bennett R, Sweeney M, Avila D Jr, Khera M.
Abstract
PURPOSE:
A history of prostate cancer has been a longstanding contraindication to the use of testosterone therapy due to the belief that higher serum testosterone causes more rapid prostate cancer growth. Recent evidence has called this paradigm into question. In this study we investigate the effect of testosterone therapy in men with untreated prostate cancer.
MATERIALS AND METHODS:
We report the results of prostate biopsies, serum prostate specific antigen and prostate volume in symptomatic testosterone deficient cases receiving testosterone therapy while undergoing active surveillance for prostate cancer.
RESULTS:
A total of 13 symptomatic testosterone deficient men with untreated prostate cancer received testosterone therapy for a median of 2.5 years (range 1.0 to 8.1). Mean age was 58.8 years. Gleason score at initial biopsy was 6 in 12 men and 7 in 1. Mean serum concentration of total testosterone increased from 238 to 664 ng/dl (p <0.001). Mean prostate specific antigen did not change with testosterone therapy (5.5 ± 6.4 vs 3.6 ± 2.6 ng/ml, p = 0.29). Prostate volume was unchanged. Mean number of followup biopsies was 2. No cancer was found in 54% of followup biopsies. Biopsies in 2 men suggested upgrading, and subsequent biopsies in 1 and radical prostatectomy in another indicated no progression. No local prostate cancer progression or distant disease was observed.
CONCLUSIONS:
Testosterone therapy in men with untreated prostate cancer was not associated with prostate cancer progression in the short to medium term. These results are consistent with the saturation model, ie maximal prostate cancer growth is achieved at low androgen concentrations. The longstanding prohibition against testosterone therapy in men with untreated or low risk prostate cancer or treated prostate cancer without evidence of metastatic or recurrent disease merits reevaluation.
J Urol. 2009 Mar;181(3):972-9. doi: 10.1016/j.juro.2008.11.031. Epub 2009 Jan 16.
Testosterone therapy in men with prostate cancer: scientific and ethical considerations.
Abstract
PURPOSE:
Pertinent literature regarding the potential use of testosterone therapy in men with prostate cancer is reviewed and synthesized.
MATERIALS AND METHODS:
A literature search was performed of English language publications on testosterone administration in men with a known history of prostate cancer and investigation of the effects of androgen concentrations on prostate parameters, especially prostatespecific antigen.
RESULTS:
The prohibition against the use of testosterone therapy in men with a history of prostate cancer is based on a model that assumes the androgen sensitivity of prostate cancer extends throughout the range of testosterone concentrations. Although it is clear that prostate cancer is exquisitely sensitive to changes in serum testosterone at low concentrations, there is considerable evidence that prostate cancergrowth becomes androgen indifferent at higher concentrations. The most likely mechanism for this loss of androgen sensitivity at higher testosterone concentrations is the finite capacity of the androgen receptor to bind androgen. This saturation model explains why serum testosterone appears unrelated to prostate cancer risk in the general population and why testosterone administration in men with metastatic prostate cancer causes rapid progression in castrated but not hormonally intact men. Worrisome features of prostate cancer such as high Gleason score, extracapsular disease and biochemical recurrence after surgery have been reported in association with low but not high testosterone. In 6 uncontrolled studies results of testosterone therapy have been reported after radical prostatectomy, external beam radiation therapy or brachytherapy. In a total of 111 men 2 (1.8%) biochemical recurrences were observed. Anecdotal evidence suggests that testosterone therapy does not necessarily cause increased prostate specific antigen even in men with untreated prostate cancer.
CONCLUSIONS:
Although no controlled studies have been performed to date to document the safety of testosterone therapy in men with prostate cancer, the limited available evidence suggests that such treatment may not pose an undue risk of prostate cancer recurrence or progression.
Eur Urol. 2016 May;69(5):894-903. doi: 10.1016/j.eururo.2015.12.005. Epub 2015 Dec 21.
Testosterone Therapy in Men With Prostate Cancer.
Kaplan AL1, Hu JC2, Morgentaler A3, Mulhall JP4, Schulman CC5, Montorsi F6.
Abstract
CONTEXT:
The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer.
OBJECTIVE:
To summarize and analyze current literature regarding the effect of testosterone replacement in men with prostate cancer.
EVIDENCE ACQUISITION:
We conducted a Medline search to identify all publications related to testosterone therapy in both treated and untreated prostate cancer.
EVIDENCE SYNTHESIS:
The historical notion that increasing testosterone was responsible for prostate cancer growth was based on elegant yet limited studies from the 1940s and anecdotal case reports. Current evidence reveals that high endogenous androgen levels do not increase the risk of a prostate cancer diagnosis. Similarly, testosterone therapy in men with testosterone deficiency does not appear to increase prostate cancer risk or the likelihood of a more aggressive disease at prostate cancer diagnosis. Androgen receptor saturation (the saturation model) appears to account for this phenomenon. Men who received testosterone therapy after treatment for localized prostate cancer do not appear to suffer higher rates of recurrence or worse outcomes; although studies to date are limited. Early reports of men on active surveillance/watchful waiting treated with testosterone have not identified adverse progression events.
CONCLUSIONS:
An improved understanding of the negative effects of testosterone deficiency on health and health-related quality of life-and the ability of testosterone therapy to mitigate these effects-has triggered a re-evaluation of the role testosterone plays in prostate cancer. An important paradigm shift has occurred within the field, in which testosterone therapy may now be regarded as a viable option for selected men with prostate cancer suffering from testosterone deficiency.
PATIENT SUMMARY:
In this article, we review and summarize the existing literature surrounding the use of testosterone therapy in men with prostate cancer. Historically, testosterone was contraindicated in men with a history of prostate cancer. We show that this contraindication is unfounded and, with careful monitoring, its use is safe in that regard.
World J Mens Health. 2018 May;36(2):103-109. doi: 10.5534/wjmh.170007. Epub 2018 Mar 22.
Shifting the Paradigm of Testosterone Replacement Therapy in Prostate Cancer.
Bell MA1, Campbell JD2, Joice G1, Sopko NA1, Burnett AL1.
Abstract
Historically, testosterone and prostate cancer have been demonstrated to have a positive association leading providers to forgo testosteronereplacement therapy (TRT) in men with concurrent histories of hypogonadism and prostate cancer. This paradigm has been gradually shifting with our evolving understanding of the relationship between testosterone and prostate cancer and the gaining popularity of the saturation model. Newer data suggests improved quality of life for men with hypogonadism after TRT leading to a more tempered view of the effects of this treatment and its risk in prostate cancer. As more reports emerge of TRT in men who have either undergone definitive treatment for prostate cancer or are on active surveillance, some providers see a role for TRT in these patients despite non-consensus in clinical guidelines. It is critical that we examine evidence currently available, while we await more rigorous data to emerge.