Let’s get right to it.
Study Details on Testosterone and Prostate Cancer
- 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 Take on This Recent Study on Testosterone and Prostate Cancer
This PLOS study 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 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’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.
Let’s look at the overall scientific work done on Testosterone and Prostate Cancer.
Stay with me here. It’s going to get good. ☺
The Relationship between Testosterone and Prostate Cancer (CaP)
Until less than ten years ago 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 heretical. In the middle of the 20th century, it was thought that T is the fuel that lit up malignancies in the prostate.
The stark connection that T propelled 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 research team 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 research team further 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 logical sequence for Dr. Huggins is 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.
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. (1)
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.
Is Testosterone the Fuel for Prostate Cancer (CaP)
In test tubes, testosterone demonstrates an increase in prostate cancer in numerous cancer cell lines but apoptosis (programmed cancer cell death) once androgens are removed. (2) A similar response is found in rat studies: androgens promote tumor progression until androgens are withdrawn – then causing regression of prostate tumor cells. (3)
From test tubes and rat studies, one can easily think, “that’s it, case closed. Testosterone fuels prostate cancer, thus low testosterone in men I best for prostate cancer prevention.”
Human studies analyzed.
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. (4)
A meta-analysis 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. (5)
Another, 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. (6)
Here’s the kicker; not only is there no causal relationship with high endogenous T and CaP but low T may cause the disease.
One such clinical trial demonstrated a high incidence rate of aggressive, more deadly type of CaP among men with low T defined as >7.6nmo/l (220ng/d). (7)
Similarly, a group of Chinese men, 110 total, showed greater high-grade CaP (higher Gleason score) in men with low T. (8)
Beyond analyzing staging with Gleason grade on biopsy, a high-risk disease has been was associated with low T after prostatectomy.
For example, 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. (9)
What should you do?
First of all, let me be clear here; I don’t have any confirmation bias towards the medical treatment with exogenous testosterone therapy. That’s not what I do as a physician. In men with low T, my goal is to prescribe lifestyle and natural methods to help the body make its own natural hormones.
Secondly, while I am not opposed to pharmaceutical testosterone therapy, once still needs to be properly managed by an experienced health care practitioner if T therapy is right for you. External T therapy by itself is a “Band-Aid” to the problem. 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.
Lastly, T therapy can safely be prescribed for the right patient, only if necessary, even after a prostate cancer diagnosis.
That’s right. Some men can increase their testosterone levels, either naturally, or with an external application, 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.
Learn what food and meals work best for prostate cancer at the live event CaPLESS Eats.
CaPLESS Eats clears up the confusion on what to eat for prostate cancer.
Closing registration at 11:59, Sunday, June 24th.
3 Blog Posts
1. Huggins C, Hodges CV; Studies on prostatic cancer: I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941.J Urol. 2002 Jul; 168(1):9-12.
2. Schwab T., Stewart T., Lehr J., Pienta K., Rhim J., Macoska J. (2000) Phenotypic characterization of immortalized normal and primary tumor-derived human prostate epithelial cell cultures. Prostate 44: 164–171.
3. Ahmad I., Sansom O., Leung H. (2008) Advances in mouse models of prostate cancer. Expert Rev Mol Med 10: e16.
4. Shaneyfelt T., Husein R., Bubley G., Mantzoros C. (2000) Hormonal predictors of prostate cancer: a meta-analysis. J Clin Oncol 18: 847.
5. Roddam A.W., Allen N.E., Appleby P., et al: Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008; 100: pp. 170-183
6. Muller R., Gerber L., Moreira D., Andriole G., Castro-Santamaria R., Freedland S. (2012) Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the reduction by dutasteride of prostate cancer events trial. Eur Urol 62: 757–764.
7. Lane B., Stephenson A., Magi-Galluzzi C., Lakin M., Klein E. (2008) Low testosterone and risk of biochemical recurrence and poorly differentiated prostate cancer at radical prostatectomy. Urology 72: 1240–1245.
8. Dai B., Qu Y., Kong Y., Ye D., Yao X., Zhang S., et al. (2012) 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. BJU Int 110: E667–E672.
9. Salonia A., Gallina A., Briganti A., Abdollah F., Suardi N., Capitanio U., et al. (2010) Preoperative hypogonadism is not an independent predictor of high-risk disease in patients undergoing radical prostatectomy. Cancer 117: 3953–3962.