I want to start our next series with a brief discussion and explanation of the relationship between the Prostate and Testosterone, real and perceived! It is a fascinating discussion because like all things Prostate related there is as much incorrect as real information, and a lot of it is from physicians and the medical community! As always, I will attempt to present information and together, we can decide what is real and what is…
The name Testosterone was coined in 1935 by Ernest Laqueur, when he isolated it from bull testes. To go even further back, John Hunter transplanted testes into carpons in 1786. Adolph Berthold postulated internal secretion from his testicular transplantation experiments in 1849. Following his observations, testicular preparations were used for therapy, popularized by self-experiments of Brown-Sequard (1889), which at best could have had placebo effects. Testis preparations were consumed until quite recently for the enhancement of virility. In the 1920’s Sergio Voronoff transplanted from animals to men, but their effectiveness was disproven by the Royal Society of Medicine in 1927. Modern androgen therapy began when Testosterone (T) was chemically synthesized independently in 1935 by Adolph Buterandt and Leopold Ruzicka.
T was ineffective when administered orally, so it was compressed into pellets or was used orally until toxic side effects became apparent and the method was abandoned. In the 1950’s longer-acting injectable T enanthate became the preferred therapeutic modality. In the 1950’s and 1960’s research concentrated on the chemical modification of androgens in order to emphasize their anabolic effects. By now anabolic steroids have largely disappeared from clinical medicine, they are still around as illegal doping. In the 1970’s the orally effective T undecanoate was added to the spectrum of preparations. In 1992 several alphabet organizations, like the World Health Organization (WHO) postulated preparations of natural T mimicking physiological serum levels, a demand first met by a transdermal scrotal film. Then in 2000 transdermal T gels became available. The most recent additions to T substitution therapy, the short-acting buccal T and the long-acting injectable T undecanoate, also fulfill the demand for physiological serum levels. (NORE: The above 2 paragraphs are from: endocrine-abstracts.org/ea/0010/ea0010s2, Title: The History of Testosterone by E. Nieschlag, 2005.)
Now that we have the useless history of Testosterone, I want to move to the origin of where Testosterone met the Prostate in medical literature. One would think this is a very long and winding road, but actually it is very simple, and very wrong as we now know. In 1942 Charles B. Huggins, a urologist from the University of Chicago, and his colleagues were experimenting on the effects of dogs that were castrated and how it affected BPH in these dogs.
Huggins and his team noted that when the dogs were castrated their prostates shrank and where they had areas that resembled human prostate cancer, these areas also shrank. Now Huggins could apply his dog results to humans. By this time, it was known (theoretically anyway) the key effect of castration on a man was to reduce the level of T in the blood stream. Now he needed to prove his theory.
To do this, Higgins needed to do some human studies. He found a group of men who had Prostate cancer that had already spread to their bones. He could lower their Testosterone levels by either castration or giving them Estrogen. A blood test called acid phosphatase was high in men with metastatic Prostate cancer and Huggins and team showed that acid phosphatase dropped substantially within days of lowering testosterone. Huggins also reported that administration of Testosterone injection to men with Prostate cancer caused acid phosphatase to rise! Huggins and his team concluded that reducing T levels caused Prostate cancer to shrink and raising T levels caused Prostate cancer to grow.
This demonstration of the androgen dependence of Prostate cancer showed great promise since before Huggins and his team’s work in the early 1940’s, Prostate cancer was considered untreatable. Going forward from this point, lowering T by castration or by adding Estrogen became the standard treatment for advanced Prostate cancer, and to many it is still the standard today! Unfortunately estrogen treatment caused heart attacks and blood clots for some men and most men did not like the idea of having their testicles removed, LHRH antagonists, a new medication, was introduced in the 1980’s. Injections of this medication is now the usual way T is lowered in men with Prostate cancer, although there are now several other medications that have been introduced in the early 2020’s as mentioned in our last post!
In 1966 Huggins received the Nobel Prize for his groundbreaking work showing that Prostate cancer grew or shrank depending on T levels. His work is still, unfortunately, considered the Gold Standard for treatment of Prostate cancer. So, our story of Prostate cancer’s dependence on T to grow or shrink has a happy and convincing conclusion, right? Well, not so fast.
As we look back on Higgins and his team’s work, some very large red flags pop up and cloud our rosy story! Is it true that adding T to Prostate cancer is like pouring gasoline on a fire, like all doctors tell us? Houston, we may have a problem because when we look at Huggins breakthrough published article we find an important issue. For something so important to all men and their health, one would assume the population for the work included thousands of patients or at the very least hundreds of patients, right? Wrong!! How about a population of one??!
In the article, Huggins reported that three men received T injections. However, results were only given for two patients; and one of them was already castrated. Now we learn that Huggin’s breakthrough work included reporting on one patient. How in heaven’s name do you do a medical research project and have data on a single patient?? Let me say it again in a different way. Dr. Huggins “advanced growth” theory was actual based on a single patient and it used a blood test that has been completely abandoned because it’s results are so erratic, the acid phosphatase blood test. Bet you cannot find anyone in 2025 that still uses that blood test for anything! Now we have cast serious doubt on the theory that T fuels Prostate cancer growth since there are no good studies to rely upon!
But come on, this Prostate Cancer and T relationship has been universally accepted for over 80 years. You are right there Batman! And there is the Memorial Sloan Kettering report from 1981 that helps the argument for Huggins. It was a study done to detail the Institute’s experience with T administration on men with metastatic Prostate cancer authored by the urologic giant of his day, Dr. Willet Whitmore and his colleagues. This ought to solve some questions for us! The study included 52 men with metastatic Prostate cancer treated over a course of 18 years. These men had been given daily T injections as a last-gasp treatment for their cancer. Of these 52 men, 45 had experienced an “unfavorable response” most within the first month of treatment.
Now here is where the fine print of this study grabs us by the throat and squeezes! Of these 52 men, all but 4 had already been treated with castration or estrogen to lower Testosterone! Not again! But yes, again we are misled by the so-called science. Of the four untreated men, one had an early unfavorable but unnamed outcome. The other 3 men continued with daily T injections for 52, 55 and 310 days with no negative effects. The authors concluded that raising T levels above the normal range did not seem to cause any cancer growth! Thus, the headline of the article only applied to patients that had already been castrated! So much for helping Dr. Huggin’s and his work!
Next we will close this loop by looking at Testosterone Flair and bring this discussion into the 21st century!
Much of the above information and future postings for this series come from the incredible book by Dr. Abraham Morgentaler called Testosterone for Life, Published by McGraw-Hill 2009. ISBN 978-0-07-149480-9
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