Long-term ‘T’ Does Not Up Risk for High-grade Prostate Cancer
Nick Mulcahy, November 25, 2015
Testosterone replacement therapy taken for up to 5 years is not associated with an increase in the risk that older men will develop high-grade prostate cancer, according to a study with more than 50,000 men with prostate cancer.
The results were published in the December issue of the Journal of Urology.
This study extends the length of time testosterone therapy, commonly known as T, has been studied in men who are subsequently diagnosed high-grade disease, explain the authors, led by Jacques Baillargeon, MD, from the University of Texas Medical Branch in Galveston.
“To date only one population-based study has been done to examine whether exposure to testosterone therapy increases the risk of high-grade prostate cancer,” they write, referring to an analysis that examined up to 1 year of testosterone therapy use before a diagnosis of prostate cancer (Urology. 2013;82:321-326).
With only a 1-year study in the medical literature, Dr. Baillargeon and his coauthors say that their “long-term” study of 5 years “offers novel and clinically relevant information to clinicians.”
The extended time period is important because of the “slow growth of prostate cancer and the unknown latency period associated with testosterone exposure,” they note.
Five years is a good length for this kind of retrospective data, Dr. Baillargeon explained.
The time that might fully cover the incubation period of prostate cancer — which is 15 years or so — would not be practical, he said. “When you require that kind of look-back period, you restrict your study sample a great deal,” Dr. Baillargeon told Medscape Medical News. Men in a major database would have to be selected at 80 years of age and older to generate 15 years of treatment history, he said.
Other studies looking at various durations of use have shown that there is no significant association between the overall incidence of prostate cancer and testosterone therapy. But these studies have not focused on the most worrisome type of early-stage prostate cancer: high-grade disease.
For their study, Dr. Baillargeon and his team used Surveillance, Epidemiology and End Results (SEER)–Medicare linked data to identify 52,519 men diagnosed with incident prostate cancer from 2001 to 2006 who had at least of 5 years continuous enrollment in Medicare before their diagnosis and who met the study criteria.
The therapy was limited to injectable forms of testosterone, which was the only type that Medicare data captured at the time. High-grade disease was indicated by a Gleason score of 8 to 10.
In the study cohort, 574 men had used testosterone in the 5 years before diagnosis and 51,945 has not. The incidence of high-grade prostate cancer was 20.1% in the testosterone users and 27.0% in the nonusers.
After adjustment for demographic and clinical characteristics, exposure to testosterone therapy was not associated with an increased risk for high-grade prostate cancer (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.67 – 1.05).
Importantly, the risk for high-grade disease did not increase as the number of testosterone injections increased (OR, 1.00; 95% CI, 0.98 – 1.01). This finding is a first in the literature, the authors report.
“No Clear Signal”
The results are heartening, a pair of experts suggests in an accompanying editorial.
“The authors found no clear signal that testosterone replacement therapy in this large population had any negative effect on the frequency of high-grade prostate cancer,” write Culley C. Carson III, MD, from the University of North Carolina at Chapel Hill, and Roger Kirby, MD, from The Prostate Center in London, United Kingdom.
The editorialists explain why testosterone replacement therapy is unlikely to spur the development of prostate cancer.
Multiple prostate-specific antigen (PSA) studies of men taking testosterone replacement therapy have shown “only modest PSA increases and then usually in those with the lowest initial testosterone,” they write.
The “saturation model” theory of testosterone and prostate cancer can explain this phenomenon, they add.
“The theory states that while prostate cancer is exquisitely testosterone sensitive at low testosterone levels, after androgen receptors are fully occupied further, testosterone does little to change prostate or prostate cancer dynamics,” Drs Carson and Kirby write.
Another expert explained the saturation model using different terms earlier this year at the American Urology Association annual meeting.
At one time, the conventional wisdom in urology was that “prostate cancer was fire and testosterone was gasoline,” said Tobias Köhler, MD, MPH, from the Southern Illinois University School of Medicine in Carbondale.
But a better analogy, he said, is that prostate cancer is a tree and testosterone is water. “You need a certain amount of testosterone for prostate cancer to develop, but if you keep piling on more and more testosterone [water], the tree doesn’t develop into a sequoia,” he explained.
This phenomenon means that it is likely safe to give testosterone therapy to men who already have prostate cancer, the editorialists point out.
“While more data are needed, healthcare providers can begin to consider treating hypogonadal patients who have prostate cancer with testosterone replacement therapy if they are symptomatic, have documented low testosterone, and are properly informed,” they write.
Dr Baillargeon, his coauthors, Dr Carson, and Dr Kirby have disclosed no relevant financial relationships.
J Urol. 2015;194:1527-1528, 1612-1616. Editorial, Abstract
Progesterone Cream Can Help Prostate Cancer
January 02, 2008 | 52,714 views
Dr. Mercola’s Comment:
I still strongly endorse progesterone, however I think the cream version has potential complications particularly by the way it accumulates and contributes to disruptions in the adrenal hormones such as DHEA, cortisol, and testosterone. I have learned that although progesterone cream is an enormously useful tool, it needs to be used very cautiously. So, if one is going to use the cream they absolutely need to be monitored with a saliva test on an annual basis. The saliva value should be below 300. I have seen numbers over 10,000 and it may take up to two years for this level to normalize as the progesterone is stored in the fat and comes out very slowly. One should not resume progesterone (in any form) until the level drops below 300 again.
Highlights from my time with Dr. John Lee
Well I had the great privilege of dining with Dr. Lee on Friday and lecturing with him on Saturday. I was expecting to learn some exciting new information and I was not disappointed. There are two major highlights to review. I am even more convinced now of the value of natural progesterone for women and even for men as I will discuss later.
The most exciting information though has to do with progesterone’s ability to PREVENT and REVERSE many cancers. The newer studies show that estrogen, specifically estradiol, does not increase the risk for breast cancer but it actually CAUSES breast cancer AND prostate cancer. There is not any debate left about this issue. All major researchers have found this The information on the prostate is new.
Let me attempt to explain the relationship for prostate cancer in more detail. Men also make estrogen and estradiol, but in much lower amounts than women. The male hormone, testosterone, is antagonist to estradiol. Testosterone prevents estradiol from causing prostate cancer by destroying the prostate cancer cells it stimulates.
Testosterone does NOT cause prostate cancer. If this were true 19 and 20 year old males would be developing prostate cancer as these are the individuals with the highest levels. This is obviously not the case. Males also produce progesterone, although about half as much as females do. The progesterone prevents the body from converting testosterone to di-hydro testosterone.
It does this by inhibiting the enzyme 5-alpha reductase. Progesterone inhibits 5 alpha reductase far more effectively than Proscar and Saw Palmetto which are the more standard agents employed in traditonal and natural medicine.
As a male ages, his progesterone level decreases just like it does in women. In women this decease occurs about the age of 35 and men about ten years later. When progesterone levels decrease, the male’s 5 alpha reductase converts the testosterone to di-hydro testosterone which is useless at removing the prostate cancer cells that estradiol stimulates. Estradiol also stimulates the enlargement of the prostate. This allows the prostate gland to swell and enlarge and in many cases transform into prostate cancer.
The prostate is embryologically similar to the female uterus. Prostate cancer is the NUMBER ONE cancer in men. Prostate enlargement is a major cause of problems in elderly men. It appears we now have a simple, safe inexpensive solution to prevent and treat this problem.
Dr. Lee’s has a large number of anecdotal stories of complete reversals of metastatic prostatic cancers. The clinical research has just begun. Dr. Lee states that there are several studies that will be published in the peer reviewed literature very shortly confirming this observation in animal studies.
There is no need to wait for these studies as there is strong biochemical evidence to support this recommendation. The January 28 JAMA had an article To die or not to die? most cells in the body die through a more subtle, noninflammatory, energy-dependent form of cell death called apoptosis.
Recent research into the molecular mechanisms of apoptosis has revealed that apoptosis is a genetically programmed process that can become deranged when the components of the cellular apoptotic machinery are mutated or present in inappropriate quantities. Dysregulation of apoptosis is associated with the cause of a wide array of diseases: cancer, neurodegeneration, autoimmunity, heart disease, and other disorders.
All cells, with the exception of brain and muscle cells, multiply continuously. The genes which regulates this cell growth are p53 and bcl2 . If the gene bcl2 dominates it will push cells to cancer. If gene p53 dominates the opposite will occur and the cell growth is controlled and the cancer do not occur.
The article clearly shows that traditional chemotherapy using poisons to stop cell hyperplasia do not work as they kill normal cells easier than cancer cells. The new idea promoted by the review is to find agents that activate p53 and deactivate bc12 is the hope for curing cancer.
Well folks, guess what the research shows??? Estradiol turns on the cancer gene bc12 and progesterone turns on the anti-cancer gene p53!!! Breast cancer cells do not multiply when women are on progesterone. These hormones also worked for cancer of the ovary and uterus and small cell lung cancer which is normally a very difficult cancer to treat with a horribly dismal diagnosis.
This is MAJOR news and will provide a radical shift in my recommendations for hormonal replacement. I know believe that nearly all men should seriously consider natural progesterone replacement sometime in their 40s, or even earlier if they have a family history of prostate cancer. There is also a reasonable likelihood that this will decrease male balding. So, all the men who wish to retain what is left of their hair, I would start this immediately.
Dr. Lee has always recommended a low dose cream. Originally, I did not believe that the low dose cream was necessary and decided to reduce the patient cost by using a high dose 10% prescription cream. This made the cream very affordable but also significantly increased the risk of overdosing and causing complications.
Dr. Lee explained to me that when much higher doses are given the excess progesterone is metabolized in the liver and some of the metabolites may have an anesthetic dose on the brain. I believe that many of the patients I have prescribed the higher dose 10% cream for have experienced some of these symptoms.
The other consideration has to do with the distribution of the dose. The progesterone cream enters from the skin into the fat. The progesterone is released from the fat into the blood stream in direct proportion to the concentration of the cream. The danger of using a higher dose cream is that there will not be a smooth release of the hormone into the blood stream over the 12 hour period.
Since progesterone has a relatively short half life of five minutes once it is in the blood, this will significantly limit its effectiveness and one will only receive partial benefits from the progesterone.
His arguments are very compelling and I am changing my recommendation to the lower dose cream. The higher dose cream was $3 per month and shifting to the lower dose cream will actually increase triple the price to about $9 per month. However, I believe the benefits are significant enough to warrant the increase in cost.
There are many low dose non prescription natural progesterone creams on the market. A typical one would have about 900 mg per two ounces which is about 1.7%. Many are available in the health food store. However, one needs to be very careful that the cream indeed has natural progesterone and in the 1.7% concentration. We will be offering one of the best low dose creams on the market, Natragest, which we obtain from Biotics Labs.
The dose of natural progesterone for men is 10 to 12 mg per day. Men do NOT need time off like women and can take the progesterone without taking any days off. The normal dose for women of natural progesterone should be about 20 mg per day from day 12 to 26.
These doses are split and taken twice a day If one is using the Natragest cream the 6 mg male dose would be about 1/16 of a teaspoon twice a day. The dose for women would be about twice that 1/8 to 1/4 teaspoon twice a day from day 12-26. It is VERY important to be a precise as possible when administering this dose.
If you are a woman and have the older higher dose cream they can still be used but I would decrease the dose to 1/32 of a teaspoon immediately.
JAMA. January 28, 1998;279:300-307