Testosterone and Prostate Cancer: Who is Right?
The prostate gland in men corresponds to the uterus in women and the two are undifferentiated in the early stages of foetal development (like testes/ovaries) and are made up of similar tissues.
When men have an erection the prostate gland becomes engorged and constricts the urethra, preventing the passing of urine, for obvious reasons. That's why it's called the prostate (Greek -- One who stands before -- an obstruction) . Both the uterus and the prostate produce PSA(prostate specific antigen), which is one reason why PSA blood tests are controversial. The prostate in males also helps control urination from the bladder, to assist in produce of the carrier fluid for sperm, to propel the sperm in ejaculation, and to assist in men getting an erection for sex.
Size definitely isn't everything where the prostate is concerned. This little gland, hidden from sight just below the bladder, is only about the size of a walnut. But when it goes rogue, a man's life can be over. Interestingly, men and those in authority wouldn't ignore the prostate if they knew what it could do to them. So why do they? Is it because the gland is invisible and out of sight is out of mind? Or that men don't want to think about any problem below the belt? Or they don't believe prostate cancer is a real problem because it doesn't hit the front-pages? Or perhaps the myth has taken hold that prostate cancer is a disease that men die with and not from.
But ask the families of some men who die of it every year in Ghana and they'll be quick to tell you another story; that prostate cancer doesn't go away if you stick your head in the sand; that it's a silent assassin which all too often takes men out in their prime; that it leaves their plans for retirement in tatters and their families grieving.
Prostate cancer: Supervillain in a comic book.
Prostate cancer strikes a special chord with me. It is a very aggressive cancer in black men, in part because it's discovered at very late stages, when it's highly advanced and there are a number of genetic mutations. After conventional treatment, this cancer comes back for 75 percent of patients. And it usually comes back in a drug-resistant form. High-grade prostate cancer is one of the biggest supervillains out there.
As a researcher, I usually don't get to work with patients. But I recently met a man who is trying to survive prostate cancer. I was deeply inspired by the optimism and strength that both Dad and son displayed and by their story of courage and support. At this event, we spoke about the different technologies directed at prostate cancer. And he was in tears as he explained how learning about these efforts gives him hope for future generations, including his son. This really touched me. It's not just about building really elegant science. It's about changing people's lives. It's about understanding the power of integrative medicine at the expense of relying solely on one treatment modality
These very aggressive prostate cancer as kind of supervillains in a comic book; prostate cancer is crafty, malleable, and they're very good at not dying. And, like most supervillains these days, their superpowers come from diverse angles and we need to stop it before it strikes
Prostate health—is crucially important to all men, so I hope all female readers will share this information with the men in their lives. Thankfully, there are simple, effective strategies men can employ that may significantly reduce their chances of having to face prostate problems such as enlarged prostate or prostate cancer, and here I discuss those strategies based on evidence.
Testosterone and Prostate Cancer: who is right?
Roger Mason in The Natural Prostate Cure says this about the recommended hormone treatment for prostate cancer:
Nearly every medical doctor in the world will tell you that testosterone is somehow “bad” for your prostate and makes prostate cancer grow. This is unquestionable Sacred Dogma - even though the fall in testosterone as men age almost exactly parallels the rise in prostate cancer, BPH, and prostatitis.
This insanity started more than eighty years ago, even before Huggins got the brilliant idea to castrate men to cure their prostate cancer! Eunuchs (castrates) had less developed sexual organs and smaller prostates, so this must have seemed like a good idea at the time. The victims seemed to get better temporarily, but the cancer soon returned with a vengeance, and they quickly died.
There are over seventy-four (74) published studies in this chapter to prove empirically that testosterone is prostate healthy. Every year more such studies are published, yet doctors still physically and chemically castrate men to reduce their levels to zero.
He goes on to say:
Again at Harvard Medical School, 8 doctors found that the cancer patients with the highest levels of testosterone fared the best and lived the longest. “A high prevalence of biopsy-detectable prostate cancer was identified in men with low total or free testosterone.” They said further, “A low serum testosterone level in men is associated with a number of medical conditions, most notably sexual dysfunction, and is commonly treated with exogenous (externally provided) testosterone supplementation.”
He cites many studies to confirm the erroneous conclusion that testosterone is the cause of prostate cancer and the fallacy that hormone treatment for prostate cancer to destroy the testosterone by drugs or castration is the best hormone treatment for prostate cancer.
How it started:
The idea that taking testosterone can cause prostate cancer originated from a single study involving a single patient back in the 1940s. Previously it was believed that high endogenous Testosterone (T) led to an increased risk of prostate cancer (CaP) – and treating prostate cancer patients with exogenous T was unconventional. In the middle of the 20th century, it was thought that T is the fuel that struck up malignancies in the prostate.
The whole idea that T pushed prostate cancer began in the early 1940’s with Dr. Charles Huggins, a Chicago University urologist and a noble prize winner for his work in demonstrating that prostate cancer growth is dependent on the serum T level. He and his cohort observed that dogs with enlarged prostates, or clinically known as benign prostatic hyperplasia (BPH) had their gland shrink after being castrated by surgical removal of the testicles.
Huggins and his cohort additional noticed that when suspicious, cancerous cells appeared in the prostates of dogs, not only did the prostate shrink after castration but so did suspicious malignant lesions. The commonsense is for Dr. Huggins to study the castrating effect in men who had advanced prostate cancer. These men either had their testicles removed or were given estrogen while having the anti-androgenic treatment effects measured by serum acid phosphatase. At that time serum Acid Phosphatase like the current PSA was the backbone of monitoring the progression of the disease.
Finally, there was a viable treatment for prostate cancer in Androgen Deprivation Therapy, it was thought, a disease with almost no cure at the time. From that point forward, lowering T to negligible levels was the standard treatment for prostate malignancies and it is still used today for advanced cases.
Huggins and his coworkers showed that acid phosphatase dropped substantially within days of lowering T in men with prostate cancer, therefore, concluding that high T enhanced prostate cancer growth and reducing T eliminated it(Huggins C, Hodges CV; Studies on prostatic cancer: The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941.J Urol. 2002.
Can testosterone cause cancer? Urologist Dr. Morgathaler demystifies it in the new era.
Since that time, much research, especially that conducted by Dr. Morganthaler, has shown that testosterone and testosterone replacement therapy is not a cause of prostate cancer. When men start hormone therapy, this is one of the most pressing questions they ask because of concern about prostate cancer. Up until recently, this question would likely have been answered by most doctors with a resounding “yes.”
However, much research has been done to determine whether the “yes” response to the question “can testosterone cause cancer?” and specifically prostate cancer is accurate. Based on accumulating evidence, it appears the answer to “can testosterone cause cancer?” is “no.” One compelling reason for the “no” response can be attributed to the investigative work done by Abraham Morganthaler, MD, FACS, author of Testosterone for Life. He evaluated the original study by urologist Charles Higgins in the 1940s, research that led to the misconception that taking testosterone can cause prostate cancer.
Morganthaler discovered that this idea arose out of one case study involving one patient. Thus, the fear that testosterone can cause cancer was based on nothing. In fact, many studies have dispelled the myth that testosterone replacement therapy causes prostate cancer or has a significant negative impact on the prostate.
A Beth Israel Deaconess Medical Center review of 72 studies found “no compelling evidence that testosterone replacement therapy increases the incidence of prostate cancer.”
A report by The Prostate Cancer Center Hamburg-Eppendorf in Germany (Isbarn 2009) stated “the available research strongly suggested that testosterone therapy neither increases the risk of prostate cancer in normal men nor causes a recurrence of the cancer in men who have been treated successfully for prostate cancer.”
In a study of 57 men who received testosterone for an average of 36 months after prostatectomy, mean testosterone levels rose in all the men before testosterone therapy. However, there was no increase in PSA values after testosterone therapy started. (Khera 2009)
A study conducted within the ongoing Osteoporotic Fractures in Men cohort looked at the association between testosterone, estradiol, estrone, and sex hormone-binding globulin and prostate cancer. Only estrone was strongly related to an increased risk of prostate cancer. (Daniels 2010)
In a landmark study, men with low testosterone levels were given testosterone injections or placebo every two weeks for six months. Before and during the study, investigators measured testosterone and DHT from blood and the prostate. Although blood concentrations of testosterone and DHT rose substantially in men who received hormone replacement, these concentrations did not change in the prostate gland. Testosterone therapy also had no effect on biochemical markers of prostate cell growth. Morganthaler noted “it is as if once the prostate has been exposed to enough testosterone, any additional testosterone is treated as excess and does not accumulate in the prostate.” Again, the answer to “can testosterone cause cancer?” is no. (Marks 2006; Morganthaler 2008)
According to a Johns Hopkins Prostate Disorders Special Report, “Testosterone-Replacement Therapy: Does It Increase Prostate Cancer Risk?” the jury is still out on whether “can testosterone cause cancer?” when men take it for a prolonged time. Morganthaler might add, as he has noted that “The relationship of testosterone to prostate cancer has undergone a significant reevaluation, and all recent evidence has reinforced the position that testosterone therapy is safe for the prostate.”
For men with prostate cancer, the concern has been that taking testosterone could make the cancer progress faster or promote tumor growth. These worries are why some doctors will not prescribe testosterone therapy for men who have a history of prostate cancer.
Morganthaler explains why this is not a concern by referring to the study by Marks and noting that “once the prostate has been exposed to enough testosterone, any additional testosterone is treated as excess and does not accumulate in the prostate.”
Basically, when men have very low testosterone levels, prostate growth is hypersensitive to any change in testosterone concentration. Therefore, while severely reducing testosterone levels with hormone therapy will cause prostate cancer to shrink, giving testosterone can cause prostate cancer to regrow. “However,” Morganthaler notes, “once we get above the point where the prostate is saturated with testosterone, adding more testosterone will have little, if any, further impact on prostate cancer growth. Experimental studies suggest the concentration at which this saturation occurs is quite low.”
The Recent Study:
A retrospective study observing 147,593 men included 58,617 in men aged 40 to 89 years with low testosterone from 2002 to 2011. 313 aggressive CaPs were diagnosed. After adjusting for age, race, hospitalization during the year before cohort entry, geography, BMI, medical comorbidities, repeated testosterone and PSA testing, testosterone treatment was not associated with incident aggressive CaP. No association between cumulative testosterone dose or formulation and CaP was observed.
My Opinion on the New Study:
The new study authored by Walsh et al 2018 titled ‘Testosterone treatment and the risk of aggressive prostate cancer in men with low testosterone levels’ published in the PLOS looked at a large population of close 150,000 men which make provides some validity to the conclusion mentioned despite it being a retrospective study.
A retrospective study looks back looks backward to determine risk or protection factors with an outcome that already happened at the start of the study. A retrospective study is the opposite of a prospective study where researchers look forward on a group of subjects before the outcome of interest happens.
Amongst researchers and scientist’ retrospective studies are not held high in its validity because there is there’s too much room for bias and confounding variables that may influence study conclusion. However, while such studies are not cause-and-effect, retrospective designs provide a vehicle for research using existing and are useful for giving preliminary data and in guiding the development of future prospective studies.
Lastly, one can compare retrospective studies with other better-designed studies to determine its clinical and biological applications. So, in my opinion, retro studies count in context to the preponderance of other published research says Dr. Geo Espinoza, renowned Naturopathic Urologist.
Is Testosterone the Fuel for Prostate Cancer (CaP)
Schwab T et al 2000 work in test tubes, testosterone establishes an increase in prostate cancer in numerous cancer cell lines but apoptosis (programmed cancer cell death) once androgens are removed. The work titled ‘Phenotypic characterization of immortalized normal and primary tumor-derived human prostate epithelial cell cultures’ and published in the journal Prostate 44: 164–171. An analogous response is found in rat studies: androgens promote tumor progression until androgens are withdrawn – then causing regression of prostate tumor cells. The research was authored by Ahmad I., Sansom O., Leung H. (2008) titled ‘Advances in mouse models of prostate cancer’ published in the journal Expert Rev Mol Med 10.
From test tubes and rat studies, one can easily think, “that’s it, case closed. Testosterone fuels prostate cancer, thus low testosterone in men is the deal for prostate cancer prevention.” So obviously for men looking for prostate cancer prevention the best is removing your testicles or castration I guess! This is insanity! Let’s look at the human studies on this
Human Studies Review:
A meta-analysis of three prospective studies controlling for testosterone, estradiol, Sex Hormone Binding Globulin (SHBG), age and body mass index (BMI) demonstrated an increase in CaP for men in the highest levels of serum testosterone but no association with DHT or estradiol. This study was conducted by Shaneyfelt T et al 2000 titled ‘Hormonal predictors of prostate cancer: a meta-analysis’ published in the J Clin Oncol 18: 847.
Another meta-analysis by Roddam A.W et al 2008 published in the J Natl Cancer Inst called the Endogenous Hormones and Prostate Cancer Collaborative Group included 3886 men diagnosed with CaP and 6438 controls. The results demonstrated no direct association between endogenous serum androgens and the development of prostate cancer.
Also, Muller R et al 2012 well-designed human clinical trial looked at 3255 men in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial, also known as the REDUCE trial. Prostate biopsies performed at two and four years revealed no relationship between testosterone or dihydrotestosterone (DHT) levels and prostate cancer risk. The work was published in the Eur Urol 62: 757–764.
Interestingly, here is the real deal; not only is there no causal relationship with high endogenous T and CaP but low T may cause the disease. One such clinical trial by Lane B et al 2008 and published in the journal Urology 72: 1240–1245 titled ‘Low testosterone and risk of biochemical recurrence and poorly differentiated prostate cancer at radical prostatectomy’ demonstrated a high incidence rate of aggressive, more deadly type of CaP among men with low T defined as >7.6nmo/l (220ng/d).
Likewise, a group of Chinese men, 110 total, showed greater high-grade CaP (higher Gleason score) in men with low T. This work was authored by Dai B et al 2012 titled ‘Low pretreatment serum total testosterone is associated with a high incidence of Gleason score 8–10 disease in prostatectomy specimens: data from ethnic Chinese patients with localized prostate cancer’ and was published in the BJU Int 110: E667–E672.
Outside evaluating staging with Gleason grade on biopsy, a high-risk disease has been associated with low T after prostatectomy. One notable case was the work authored by Salonia A et al 2010 titled ‘Preoperative hypogonadism is not an independent predictor of high-risk disease in patients undergoing radical prostatectomy’ published in the journal Cancer 117: 3953–3962. The work revealed that in 673 men undergoing prostatectomy had their morning T levels taken with surgical pathology outcomes and observed a significant risk of advanced disease that included seminal vesicle invasion in severely hypogonadal men.
Adverse Reactions on Prostate Cancer Hormone Therapy: Studies
A study which was published in the Journal of the American Medical (JAMA) Association has shown that men who undergo hormone therapy for prostate cancer are dramatically at greater risk of kidney failure, heart attacks and strokes.
The study found for every 1,000 men who undergo hormone therapy for five years, there will be an additional 360 cases of diabetes, 315 cases of heart disease, 42 strokes and 28 heart attacks in addition to being 2.5 times more likely to suffer kidney failure. (http://consumer.healthday.com/cancer-information-5/mis-cancer-news-102/adt-and-kidney-failure-678336.html)
Another study looked at the records of 30,642 Swedish men with locally advanced or metastatic prostate cancer who had received hormone therapy between 1997 and 2006 and compared their rates of heart problems with those of the general Swedish population.
This study revealed that there is an elevated risk of heart problems associated with prostate cancer hormone therapy and even more worrisome, the problems began only months into the treatment. The study lead to the American Cancer Society quoting “Hormone therapy does not cure prostate cancer” on their website. (http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-hormone-therapy)
Another article published in JAMA found that there is no improvement for life expectancy when treated by hormone therapy. Lu-Yao of the Cancer Institute of New Jersey conducted a study of 19,271 men aged over 66 who were diagnosed with localized Stage 1 or 2 prostate cancer. Of these men 41% received hormone therapy and the rest received conservative management including watchful waiting.
The study found the survival rate of men receiving hormone therapy was 80.1% whereas the survival rate of the other group was 82.6%, meaning the hormone therapy group had a lower survival rate. (http://www.medicalnewstoday.com/articles/114023.php)
Prostate Cancer Hormone Treatment – A Viable Option?
The purpose of hormone therapy for prostate cancer is to stop the male hormone, testosterone, from stimulating prostate cancer cells by blocking or reducing the testosterone produced in the body. This form of treatment is under intense scrutiny as it carries huge, irreversible risks and dangers with little or no benefits. By looking at the types of prostate hormone therapy, their side effects, studies and alternatives it is clear that offering this type of treatment is boarding on negligence from the medical professionals.
Prostate Cancer Hormone Therapy: Types
Orchiectomy (surgical castration)
Although a type of surgery, this method is used as a form of hormone therapy. The operation involves a surgeon removing the testicles where the body makes most of the androgens (testosterone). By doing this the prostate cancer will cease to grow or shrink for a period of time, however, the procedure is permanent.
Luteinizing hormone-releasing hormone (LHRH) analogs
These drugs are designed to lower the amount of testosterone made by the testicles and is commonly known as chemical castration because the lower androgen levels just as effectively as orchiectomy. The drugs allow the testicles to remain; however, they will shrink over time and eventually become too small to feel.
These drugs are the most popular form of prostate cancer hormone treatment and taken either by injection or as small implants under the skin. LHRH analogs include; leuprolide (Lupron, Eligard), goserelin (Zoladex), triptorelin (Trelstar), and histrelin (Vantas).
The side effects that occur alongside hormone therapy for prostate cancer are unavoidable and irreversible, and have been recognized as such by medical professionals. “The side effects….are part and parcel of that particular approach to therapy,” said Durado Brooks, director of prostate and colorectal cancer at the American Cancer Society.
The most common side effects include:
- Decreased mental capacity, feelings of depression and tiredness
- Decreased bone and muscle mass
- Weight gain
- Hot flashes
- Sore breasts/ growth of excess breast tissue
On top of these side effects there is the loss of sex drive, erectile dysfunction and other general sexual problems. The effects of this can be destructive to your relationship, masculinity and overall happiness. Prostate Cancer UK have provided answers to the questions most men ask regarding sexual problems relating to prostate cancer hormone treatment and although a positive spin has been put on the answers it is clear that the effects are devastating.
Why Testosterone is significant to Men’s Health?
The testosterone definition plays a very critical role when determining the health and sexual well-being of men. Research has shown that testosterone or the lack of it can have detrimental effects on a man’s body. It is important to know what testosterone is and how it is defined before delving into its effects on the human body. To define testosterone, in mammals, testosterone can be said to be the chief sex hormone secreted by the testes in males and by the ovaries in females. Adrenal glands also secrete small amounts of testosterone.
At times it is also used as an anabolic steroid. The testosterone definition in men plays an imperative part in the process of development and growth of reproductive system tissues such as the prostate and testis. Testosterone also plays a very critical role in giving rise to secondary sexual characteristics like increasing bone mass and muscle mass. It also brings forth body hair growth. Studies have shown that testosterone is important to keep away osteoporosis. Testosterone levels peak to about 7-8 times greater in males as compared to females on an average, but the daily levels are about 20 times higher.
Recommendation for Patients:
As with all my write ups and practice based on objective and not subjective as holistic practitioner who has conducted extensive research in the field of holistic urology; I don’t have any endorsement bias towards the medical treatment with exogenous testosterone therapy. That is not what I do as a holistic practitioner and researcher. Considering men with low T, the aim is to prescribe lifestyle and natural methods to help the body make its own, natural hormones.
Additionally, I am not against pharmaceutical or conventional testosterone therapy as I have advised several men based on their condition to opt for it, but one still needs to be properly managed by a knowledgeable practitioner if T therapy is right for you and you considering as low T has several side effects. External T therapy by itself is a “Band-Aid” to the problem says Geo Espinoza. “It’s a good temporary solution (good long-term solution in some cases), but it is not a cure. The long-lasting remedy usually lies in a lasting lifestyle change”.
Causes of low testosterone include chronic high-stress mismanagement, poor sleep habits, lack of physical activity, being overweight, metabolic syndrome…you know, the typical culprits to most health problems. Finally, T therapy can carefully be prescribed for the right patient, only if needed, even after a prostate cancer diagnosis. You should be monitored closely for any rise in PSA levels and/or return of prostate cancer. Avoid synthetic testosterone. Instead, you can also ask your Doctor or Urology about bio-identical testosterone therapy. This form of the hormone mimics the activity of the testosterone naturally produced by the body.
Have your physician balance testosterone with estradiol. The proper testosterone:estradiol ratio is necessary for prostate (and overall) health. Another fear associated with taking testosterone is that the prostate begins to grow. This increase in size usually stops after the first few months of treatment. Thus the prostate typically ends up being no larger than it was before the hormone level began to drop.
In conclusion: the increase in prostate size resulting from testosterone therapy is not usually sufficient to cause urinary symptoms associated with BPH or to worry about “can testosterone cause cancer?”
That’s right. Some men can increase their testosterone after prostate cancer diagnosis. Once we look at much of the research, we can see the PLOS study having some validity despite its retrospective design. Let's look at this logically. Testosterone is what makes us men. Lowering it is one of the real main "causes" of prostate cancer. Of course, it is what triggers this loss of testosterone while at the same time increasing estrogen to dangerous levels that we must learn about. You may not even realize that we consume so many foods laced with chemicals that our bodies are fighting to survive. There are hormone disruptors in the typical mainstream western diet: pesticides, herbicides and fungicides of non-organic food; chemicals that are leached into food and water from plastic bottles and food can linings; and, all the way to the cleaners you use in your house and the non-stick surfaces in your pots and pans.
These toxins in our food supply and environment are what we need to pay attention to. The result is a lowering of testosterone in men coupled with a drastic rise of estrogens resulting in cancers. The solution is to stop the onslaught of the toxins by modifying the diet and to clean. Low testosterone levels (not high ones) combined with high estrogen levels are the real underlying conditions that cause prostate disease. Remember that prostate cancer is a natural reaction of your body to protect itself from harmful toxic build-up in your body. Better to sacrifice the prostate with cancer than to allow cancer cells to migrate throughout your body. This is your body wisdom at work.
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