Dr. Weeks’ Comment: Given that men facing prostate cancer are weighing life and death decisions, and given Stanford Medical School’s reputation as fine center utilizing scientific methodology, I think you will agree with me, upon reading the following references, that doctors at Stanford should be ashamed of themselves for parroting an old and long since invalidated medical myth the perpetuation of which creates great suffering today.
A client was recently evaluated at the Stanford Health Care Department of Radiation Oncology for his newly diagnosed prostate cancer. No surprise when they recommend the standard of care which involves debilitating treatment protocols and occasions severe and permanent side-effects – one of which is androgen blockage (chemical castration). The doctors at Stanford advised: “Androgen Deprivation Therapy (ADT): This treatment modality is used in conjunction with radiation therapy, and it may not be appropriate for all patients. Duration of treatment: 4 to 36 months and is dependent upon disease staging and individual patient factors. This treatment may include a combination of oral therapy and injection therapy. We use it to temporarily suppress the body from making testosterone. Testosterone has been shown to cause the progression of prostate cancer”
Why would Stanford caution against the use of testosterone and actually recommend androgen blockade (chemical castration)? Here is why: because of a now disproven belief that “testosterone is like throwing gasoline on the fire.” A Dr. Charles Huggins received the Nobel Prize in Medicine in 1966 for shoddy and irresponsible research done in 1941 which today would not even merit publication in a peer-reviewed scientific journal. As my friend Dr. Abe Morgentaler – urologist at Harvard, so eloquently describes in his breakthrough book: Testosterone for Life, the assertion that testosterone is dangerous for men with prostate cancer derived from analyzing the data of three men with prostate cancer who received testosterone after their diagnosis: of the three, only two were reported on and of the two, one of the two men had been castrated and the other not. So the “gas on the fire” stigma resulted from giving testosterone to one man who had not received prior hormonal manipulation.
But what does the current research show? Go to Pub Med and enter the search term “prostate cancer” and “testosterone” and ALL the citations do NOT endorse Stanford’s disappointing advice. Only when testosterone metabolizes to estrogen (a know carcinogen) does the risk of prostate cancer increase.
Let’s look for ourselves at current peer reviewed scientific articles:
“…not only did testosterone replacement not increase recurrence, but it actually lowered recurrence rates. While the testosterone is not curing the cancer per se, it is slowing the growth of the cancer, giving an average of an extra 1.5 years before traces of cancer can be found. We already know that testosterone can help with physiological markers such as muscle mass, better cholesterol and triglyceride levels and increased sexual activity, so this seems to be a win-win…”
and
“…we need to question the taboo against testosterone use in prostate cancer therapy…”
PUBLIC RELEASE: 16-MAR-2019
https://www.eurekalert.org/pub_releases/2019-03/eaou-tsp031419.php
Testosterone slows prostate cancer recurrence in low-risk patients
EUROPEAN ASSOCIATION OF UROLOGY
In the largest such study so far undertaken, US researchers have shown that testosterone replacement slows the recurrence of prostate cancer in low-risk patients. This may call into question the general applicability of Nobel-Prize winning hormonal prostate treatment. The work is presented at the European Association of Urology congress in Barcelona.
Background
Doctors have long regarded testosterone as a hormone which promotes prostate cancer. The 1941 work of Huggins and Hodges won Huggins the 1966 Nobel Prize for Medicine*, for reporting the dramatic impact of testosterone reduction on prostate cancer. Since then, medicines which reduce levels of the hormone testosterone have become a standard option for many patients**.
However, in the late 1990s to 2000s, doctors discovered that although men on long term anti-testosterone treatments were not dying from prostate cancer, they were dying prematurely of cardiovascular disease. It seemed that although anti-testosterone therapies were treating the prostate cancer, the extremely low testosterone levels were significantly worsening metabolic complications such as elevated blood sugar, diabetes, elevated cholesterol, mid-abdomen visceral fat, etc. Low testosterone also caused a loss of sexual function in many men on anti-androgen treatment. This led some doctors*** to suggest testosterone treatment of some low risk men after radiation or surgical treatment.
What have they done?
Starting in 2008 a team of doctors from the University of California, Irvine, led by Professor Thomas Ahlering, began to carefully select patients for testosterone replacement after primary treatment of prostate cancer with robotic radical prostatectomy, in hopes of improving recovery of sexual function.
The team worked with 834 patients undergoing radical prostatectomy. They treated 152 low-risk patients with no evidence of disease with testosterone replacement therapy. After a median of 3.1 years following surgery, they tested the patients for biochemical recurrence of the cancer, as indicated by measurement of the Prostate Specific Antigen (PSA) levels. They found that the cancer had recurred in only approximately 5% of treated patients, whereas the cancer had recurred in 15% of the patients who did not receive testosterone. Overall, after accounting for differences between the groups, they found nearly a three-fold reduction by three years.
Importance
Thomas Ahlering commented “This is not what we set out to prove, so it was a big surprise: not only did testosterone replacement not increase recurrence, but it actually lowered recurrence rates. While the testosterone is not curing the cancer per se, it is slowing the growth of the cancer, giving an average of an extra 1.5 years before traces of cancer can be found. We already know that testosterone can help with physiological markers such as muscle mass, better cholesterol and triglyceride levels and increased sexual activity, so this seems to be a win-win”.
He continued, “There have been smaller studies which have hinted that testosterone may not be risky for certain patient groups, but this is the largest such study ever conducted. We’re not suggesting that treatment methods be changed just yet, but this puts us at the stage where we need to question the taboo against testosterone use in prostate cancer therapy – especially for low-risk patients after radical prostatectomy. We need the oncology/urology community to begin to review testosterone use”.
Commenting, Professor Francesco Montorsi (Milano), European Association of Urology’s Adjunct Secretary General for Science said:
“The paper is indeed important, as it stresses the importance of checking testosterone levels as a part of the management of patients with sexual disorders following radical prostatectomy. Obviously selection of the right patients is vital, but if confirmed, this may have immediate benefits on quality of life; the possibility of reducing mortality would be an unexpected bonus. We now need bigger studies to support this work”.
###
Notes
*See Nobel citation https://www.nobelprize.org/prizes/medicine/1966/huggins/facts/
**For background on hormonal treatment see https://www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html
***notably Dr Abraham Morgentaler
Funding: no external funding was received in support of this work.
AND
“…The fears of testosterone therapy (TTh) causing or worsening prostate cancer do not appear to be well supported by available data…”
Curr Urol Rep. 2018 Jun 30;19(8):67. doi: 10.1007/s11934-018-0812-1.
The Role of Testosterone Therapy in the Setting of Prostate Cancer.
Rodriguez KM1, Pastuszak AW2,3, Khera M4.
Abstract
PURPOSE OF REVIEW:
The role of testosterone in the development of prostate cancer and the safety of testosterone therapy (TTh) after prostate cancer treatment, or in the setting of active surveillance, remains controversial. There are many concerns about using TTh in men, particularly those with a history of prostate cancer, ranging from a possible increased risk of cardiovascular disease to cancer progression or recurrence. With many prostate cancer patients living longer, and hypogonadism having significant morbidity, much care must go into the decision to treat. Here, we review the literature investigating the effects of testosterone on the prostate as well as the efficacy and safety of exogenous testosterone in men with a history of prostate cancer.
RECENT FINDINGS:
The improvement in quality of life with TTh is well studied and understood, while the argument for significantly increased risk of cancer or other adverse effects is much less robust. Neither increased rates of prostate cancer, cancer recurrence, or cardiovascular risk have been well established. In men with high-risk prostate cancer, evidence in the setting of TTh is very limited, and TTh should be used with caution. The fears of TTh causing or worsening prostate cancer do not appear to be well supported by available data. Though more studies are needed to definitively determine the safety of TTh in men with prostate cancer, consideration should be given to treatment of hypogonadal men with a history of CaP.
AND
“…modern evidence suggests that testosterone replacement is a safe and effective treatment option for hypogonadal men with non-high-risk prostate cancer…
ex Med Rev. 2016 Oct;4(4):376-88. doi: 10.1016/j.sxmr.2016.06.005. Epub 2016 Jul 27.
Testosterone Therapy Among Prostate Cancer Survivors.
Abstract
INTRODUCTION:
The use of testosterone in men with a history of prostate cancer remains controversial in light of established findings linking androgens to prostate cancer growth. However, hypogonadism significantly affects quality of life and has negative sequelae, and the risks and benefits of testosterone therapy might be worthwhile to consider in all men, even those with a history of high-risk prostate cancer.
AIM:
To discuss the effects of testosterone on the prostate and the use of testosterone therapy in hypogonadal men with a history of prostate cancer.
METHODS:
Review of the literature examining the effects of testosterone on the prostate and the efficacy and safety of exogenous testosterone in men with a history of prostate cancer.
MAIN OUTCOME MEASURES:
Summary of effects of exogenous and endogenous testosterone on prostate tissue in vitro and in vivo, with a focus on effects in men with a history of prostate cancer.
RESULTS:
Testosterone therapy ameliorates the symptoms of hypogonadism, decreases the risk for its negative sequelae, and can significantly improve quality of life. Recent studies do not support an increased risk for de novo prostate cancer, progression of the disease, or biochemical recurrence in hypogonadal men with a history of non-high-risk prostate cancer treated with testosterone therapy. Evidence supporting the use of testosterone in the setting of high-risk prostate cancer is less clear.
CONCLUSION:
Despite the historical reluctance toward the use of testosterone therapy in men with a history of prostate cancer, modern evidence suggests that testosterone replacement is a safe and effective treatment option for hypogonadal men with non-high-risk prostate cancer.Additional work to definitively demonstrate the efficacy and safety of testosterone therapy in men with prostate cancer is needed, and persistent vigilance and surveillance of treated men remains necessary.
AND
“…testosterone replacement therapy in men with a history of prostate cancer, treatment was not associated with increased overall or cancer-specific mortality..”.
J Sex Med. 2014 Apr;11(4):1063-1070. doi: 10.1111/jsm.12429. Epub 2014 Jan 21.
Testosterone replacement therapy following the diagnosis of prostate cancer: outcomes and utilization trends.
Kaplan AL1, Trinh QD2, Sun M3, Carter SC4, Nguyen PL5, Shih YT6, Marks LS4, Hu JC4.
Abstract
INTRODUCTION:
Late-onset hypogonadism may impair quality of life and contribute to metabolic and cardiovascular comorbidity in aging men. Testosterone replacement therapy is effective in treating hypogonadism. However, for the millions of men with a history of prostate cancer, exogenous testosterone has long been considered contraindicated, even though little data in such men are available. Clarification of this safety issue could allow treatment to be considered for a sizeable segment of the aging male population.
AIM:
The aim of this study is to examine population-based utilization and impact of testosterone replacement therapy in men with prostate cancer.
METHODS:
Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified 149,354 men diagnosed with prostate cancer from 1992 to 2007. Of those, 1181 (0.79%) men received exogenous testosterone following their cancer diagnosis. We used propensity scoring analysis to examine the effect of testosterone replacement on the use of salvage hormone therapy and overall and prostate cancer-specific mortality.
MAIN OUTCOME MEASURES:
We assessed overall mortality, cancer-specific mortality, and the use of salvage hormone therapy.
RESULTS:
Following prostate cancer diagnosis, testosterone replacement was directly related to income and educational status and inversely related to age (all P < 0.001). Men undergoing radical prostatectomy and men with well-differentiated tumors were more likely to receive testosterone (all P < 0.001). On adjusted analysis, testosterone replacement therapy was not associated with overall or cancer-specific mortality or with the use of salvage hormone therapy.
CONCLUSIONS:
In this population-based observational study of testosterone replacement therapy in men with a history of prostate cancer, treatment was not associated with increased overall or cancer-specific mortality.These findings suggest testosterone replacement therapy may be considered in men with a history of prostate cancer, but confirmatory prospective studies are needed.
AND
“…The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism…
Asian J Androl. 2015 Nov-Dec;17(6):878-81; discussion 880. doi: 10.4103/1008-682X.150841.
Testosterone replacement therapy and the risk of prostate cancer.
Warburton D, Hobaugh C, Wang G, Lin H, Wang R1.
Abstract
Understanding the role of testosterone replacement therapy (TRT) in the development and progression of prostate cancer is an important concept in treating patients with symptoms of hypogonadism. This article revealed a small number of mostly retrospective, observational studies describing the use of TRT in the general population, in men with prostatic intraepithelial neoplasia (PIN), in men with a history of treated prostate cancer, and in men on active surveillance for prostate cancer. The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism, and the prostate saturation theory provides a model explaining the basis for these results. The use of TRT in men with a history of prostate cancer is considered experimental, but future results from randomized controlled trials could lead to a change in our current treatment approach
AND
“…there is no convincing evidence that the normalization of testosterone serum levels in men with low levels presents a deleterious effect on the evolution of the disease…”
Curr Urol Rep. 2009 Nov;10(6):453-9.
Testosterone therapy and prostate carcinoma.
Abstract
Hypogonadism is a clinical and biochemical syndrome associated with a range of disease states that has significant effects on morbidity and mortality and also affects quality of life. Because of the increase in life expectancy and prostate carcinoma (PCa) survival, a significant increase in the number of men with hypogonadism who have undergone presumably curative treatment of PCa is anticipated. Despite the widespread belief regarding contraindication of testosterone administration to men with known or suspected PCa, there is no convincing evidence that the normalization of testosterone serum levels in men with low levels presents a deleterious effect on the evolution of the disease. In the few available case series describing testosterone replacement therapy (TRT) after treatment of PCa, no case of clinical or biochemical progression was observed. The available data suggest that TRT can be cautiously considered in selected hypogonadal men previously treated for curative intent of low-risk PCa and without evidence of active disease.