Does Testosterone Cause Prostate Cancer? Can Men Treated for Prostate Cancer Use TRT?

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Nelson Vergel

Founder, ExcelMale.com
This is an excerpt from my book

Ensuring Prostate Health—No Link Found Between Androgen Levels and Risk for Prostate Cancer

The prostate is a gland that is part of the male reproductive system. Its function is to store and secrete a slightly alkaline (pH 7.29) a milky fluid which usually constitutes 25-30% of the volume of the semen along with spermatozoa. This alkaline fluid seems to neutralize the acidity in the vagina, prolonging the lifespan of the sperm. Also, the prostate contains some smooth muscles that help expel semen during ejaculation. It also helps control the flow of urine during ejaculation.

A healthy human prostate is classically said to be slightly larger than a walnut. In actuality, it is approximately the size of kiwi fruit. It surrounds the urethra just below the urinary bladder and can be felt during a rectal exam.




Prostate cancer


This little gland attracts a great deal of attention in men’s health. One of the major issues is related to cancer. Prostate cancer is one of the leading causes of death in men in the United States. As men age, small hidden prostatic lesions become increasingly common. These may or may not become cancerous. These lesions occur in 30 percent of American men over the age of 45, with the prevalence rising to more than 80 percent for men over the age of 80. Genetic factors and lifestyle conditions such as diet are believed to contribute to this transformation.

Doctors use different methods to detect prostate cancer, including prostate-specific antigen (PSA) assays, digital rectal examination (DRE), and transrectal ultrasound. A DRE before starting testosterone replacement therapy and every six months are recommended, especially for men with a family history of prostate cancer or those older than 40 years. Nobody likes having a DRE but your continued good health is worth a few seconds of discomfort. An abnormal rectal exam, a confirmed increase in PSA greater than 2 ng/mL, or PSA of over 4 ng/mL will prompt a health care provider to refer you to a urologist for further evaluation (usually an ultrasound and prostate biopsies).

Admittedly the PSA and the DRE lack sensitivity and specificity. 25 percent of patients with prostate cancer have normal PSA levels (false negatives), while benign prostatic hyperplasia (BPH), a non-cancerous inflammation, may elevate them (false positives). Researchers have found hidden prostatic lesions with needle biopsies in some men with normal PSA level and normal transrectal ultrasound findings. Prostate biopsies are part of routine clinical use of testosterone therapy and are not justified unless a sharp rise in PSA is observed and infections have been ruled out.

There has some been confusion regarding testosterone replacement therapy’s role in PSA elevation or causing prostate cancer. Prostate cancer is initially androgen-dependent so testosterone therapy should not be used by men with prostatic cancer. This does not mean that it causes cancer. A huge pooled analysis of data from 18 studies (consisting of 3,886 men with prostate cancer and 6,438 controls), published in the February 6, 2008 issue of theJournal of the National Cancer Institute found that blood levels of androgens and other sex hormones do not seem to be related to an increased risk for prostate cancer. In short, testosterone therapy does not appear to cause prostate cancer but it can make it worse.


This video explains in more details the misconceptions not only affect testosterone replacement and prostate cancer but also about heart disease:




Prostate infection

Another health concern is prostatitis or prostate infection. This is common in aging men and can be a leading cause of an elevated PSA. Your doctor will want to check you for infection if your PSA unexpectedly increases by checking your urine for white blood cells. If they are high, he may refer you to a urologist who would induce a discharge from your penis to look at it under the microscope. Don’t ask me how the urologist does it, ask the urologist!
Benign prostatic hyperplasia.

A common health condition is benign prostatic hyperplasia or BPH. It is estimated to occur in 50 percent of men older than 50 years. Increased frequency of urination, frequent trips to the bathroom at night, incomplete voiding, and urgency to urinate indicate possible prostatic inflammation. BPH does not necessarily lead to increased rates of prostate cancer. There have been no prospective, controlled, long-term studies on the effects of testosterone administration on either the development or the progression of BPH. One open-label, one-year study that measured prostate size using ultrasound found no increase during testosterone replacement therapy, suggesting that the treatment does not cause BPH. Whether testosterone treatment worsens asymptomatic BPH has not been established. Some individuals are more prone to prostatic inflammation when using testosterone.

Another study was conducted by Dr. Michael D. Trifiro at Moores UCSD Cancer Center in San Diego. Dr. Trifiro observed 158 men for 20 years to determine the correlation between serum sex hormones and lower urinary tract symptoms (reduced urinary flow, urgency, and other symptoms associated with BPH). The researchers found no significant associations of total testosterone, estradiol (E2), testosterone: E2 ratio, DHT, or dehydroepiandrosterone with lower urinary tract symptoms or with any measured hormones(published in BJU International in December 2009).

Testosterone replacement therapy is not contraindicated in those with BPH. Men with BPH who need to start testosterone replacement should be observed very closely. The first symptom that worsens with increased BPH is restricted urinary flow and urgency, especially during sleep hours. Many urologists are successfully prescribing medications to ease those symptoms and improve urinary flow in men with BPH. Finasteride (brand name: Proscar), which was approved by the FDA in 1992, inhibits the production of dihydrotestosterone (DHT), which is involved with prostate enlargement. Its use can actually shrink the prostate in some men. However, many men using Proscar complain of erectile dysfunction (DHT receptors may be involved in healthy erections). For men who experience this side effect, other medications may be of help. Proscar has also been found to decrease the risk of prostate cancer in men by 25 percent over a seven-year period. More studies are ongoing.

The FDA approved the drugs terazosin (brand name: Hytrin) in 1993, doxazosin (Cardura) in 1995, and tamsulosin (Flomax) in 1997 for the treatment of BPH. All three belong to the class of drugs known as alpha blockers. They work by relaxing the smooth muscle of the prostate and bladder neck to improve urine flow and to reduce bladder outlet obstruction.

Terazosin and doxazosin were developed first to treat high blood pressure. Tamsulosin is the first alpha-blocker developed specifically to treat BPH. The main side effects of these drugs are nasal congestion, lowered blood pressure, and rash or itching. Most men using them report fast improvements in their urine flow within one to three days. They end up not having to get up in the middle of the night to urinate, so they sleep better and feel less fatigued during the day.

The most common nonprescription agent used to alleviate symptoms of BPH is the over-the-counter herb saw palmetto (Serenoa repens). Extracted from the berry of the saw palmetto shrub, this substance is thought to inhibit 5-alpha-reductase (5-·R), thus blocking the conversion of testosterone into DHT, which is responsible for stimulating the growth of the prostate gland.

Saw palmetto is generally well tolerated; side effects are infrequent but include headache and gastrointestinal upset. No known drug interactions are associated with the use of this herb. Some studies found that saw palmetto led to an increase in urine flow rate in men with BPH compared with placebo, with effects comparable to finasteride.

One randomized, double-blind, placebo-controlled study followed men with BPH who took standardized saw palmetto extract 160 mg or placebo twice daily for one year. There was no significant difference found between the saw palmetto and placebo groups in standardized objective urinary symptoms. The incidence of side effects was similar in the two groups. These results cast considerable doubt on the effectiveness of saw palmetto for the treatment of BPH.

Patients who cannot tolerate BPH medications are now using emerging techniques like lasers to vaporize obstructing prostate tissue. Talk to your urologist about this if you’re interested. Be careful with its main side effect: you stop ejaculating forward (retrograde ejaculation into your bladder).

PERSONAL COMMENT: After using testosterone for 17 years, I started to develop a weak urine flow. My doctor gave me prescriptions for several alpha blockers (Uroxatral, Flomax, etc). They worked great but I experienced a rash with each one. My urologist found a prostate infection, which he treated with antibiotics. The infection seemed to linger for months. I then received an ultrasound of my prostate. This test showed that my prostate was not enlarged. Instead, it showed that a calcification, caused by a chronic prostatic infection, was blocking my urine flow through my prostate. I got the green light laser procedure done to open up my urethra. It worked great. So, what may seem like BPH may not be! Prostatic infections often go untreated for months since in many cases we may not have symptoms.


Here are more studies about testosterone and prostate cancer:

Testosterone Replacement in Men Treated for Prostate Cancer

Testosterone Replacement in Men with History of Prostate Cancer Found Safe

Testosterone Replacement Side Effect Management- Interview with Dr Michael Scally


 

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Nelson Vergel

Founder, ExcelMale.com
A long-held belief is that testosterone causes prostate cancer or accelerates its growth. This so called “androgen hypothesis” arose from a small study in the 1940s. Medical students and doctors have been taught ever since that high testosterone levels promote the development of prostate cancer, that low testosterone is protective, and that the administration of testosterone to a man with existing prostate cancer is like "pouring gasoline on a fire.'' This fear is also the most common reason for doctor's reluctance to prescribing testosterone replacement therapy, even in hypogonadal men. - See more at: https://www.brinkzone.com/general-health/testosterone-and-prostate-cancer-bye-androgen-hypothesis-welcome-saturation-model/#sthash.cq8JlI3K.dpuf
 

Nelson Vergel

Founder, ExcelMale.com
Long-term testosterone treatment in hypogonadal men does not increase their risk for prostate cancer (PCa), according to a study presented at the American Society of Clinical Oncology annual meeting in Chicago.

The study, by Ahmad Haider, MD, who is in private practice in Bremerhaven, Germany, and colleagues, included 942 hypogonadal men who underwent long-term testosterone treatment at 3 German centers (cohorts A, B, and C). Patients received testosterone undecanoate for up to 16 years.

Cohort A included 300 patients with a mean age of 57.7 years). PSA levels increased significantly from 1.77 to 2.0 ng/mL and mean prostate volume rose significantly from 28.3 to 30.7 mL. PCa was diagnosed in 5 patients (1.7%), for an incidence of 39.4 cases per 10,000 patient-years.

Cohort B had 261 patients with a mean age of 59.5 years. PSA levels increased significantly from 0.86 to 1.38 ng/mL and prostate volume increased significantly from 27.9 to 36.9 mL. PCa was diagnosed in 6 men (2.3%), for an incidence of 54.5 cases per 10,000 patient-years.

Cohort C had 381 patients with a mean age 42.6 years. PSA levels increased significantly from 1.6 to 1.9 ng/mL and prostate volume increased significantly from 16.9 to 19.9 mL. No case of PCa was diagnosed in this group.

The investigators pointed out that the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC) found a PCa incidence of 116 and 96.6 cases per 10,000 patient-years, respectively. Dr. Haider's group concluded that the PCa incidence found in their study does not suggest an increased risk of PCa in hypogonadal men on long-term testosterone treatment.

https://www.renalandurologynews.com/long-term-testosterone-therapy-does-not-raise-pca-risk/article/351136/
 

Nelson Vergel

Founder, ExcelMale.com
Testosterone Replacement Replacement (TRT) and Prostate Cancer Myth

"One myth is that TRT contributes to worsening benign prostatic hyperplasia (BPH) and to an increase in the risk of urinary retention. In a retrospective review of 120 hypogonadal men treated with TRT over a 10-year period, TRT was actually associated with a lower risk of worsening lower urinary tract symptoms (LUTS). Among 52 men randomly assigned to receive TRT versus placebo for 1 year, investigators found that LUTS, flow rates and volumes voided were significantly better in the TRT group than in the placebo group.

Another common misconception is that TRT increases a man's risk of developing prostate cancer. Importantly, TRT has not been associated with clinically significant increases in prostate-specific antigen (PSA) or an increased risk of prostate cancer. In a systematic review of published studies of TRT in men with hypogonadism, the average PSA increase after initiation of TRT was 0.3 ng/mL in hypogonadal men under 65 and 0.4 ng/mL in men over 65. The practice of using TRT as a “stress test” to determine whether PSA will rise or unmask clinically unapparent prostate cancer is not supported by science. Consequently, significant increases in PSA among men on TRT should not be solely attributed to the use of TRT and should be investigated irrespective of TRT use.

No association has been established between endogenous testosterone concentrations and PSA, or the risk of developing prostate cancer. However, among men with prostate cancer, low endogenous testosterone has been associated with adverse prognostic features, including higher stage cancer, higher Gleason scores, higher frequency of positive surgical margins, and decreased overall survival with metastatic disease.

Consistent with previous smaller investigations, in a review of 103 hypogonadal men with prostate cancer and a undetect- able PSA following radical prostatectomy treated with TRT, there were no differences in the rates of biochemical recur- rence compared to a reference group of 50 non-hypogonadal men. Among both groups, all biochemical recurrences were seen in men with high-risk features (Gleason score 8 or higher, positive surgical margins or lymph nodes), suggesting that the characteristics of the cancer themselves drive recurrences versus testosterone levels or replacement.

In a study of 13 hypogonadal men with untreated prostate cancer undergoing active surveillance, TRT for a median of 30 months was not associated with increased PSA levels or prostate cancer progression."

Source: Can Urol Assoc J 2014;8(7-8):S145-7.
 

Nelson Vergel

Founder, ExcelMale.com
Testosterone Replacement in Men with History of Prostate Cancer Found Safe



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, 1,181 (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 . Men undergoing radical prostatectomy and men with well-differentiated tumors were more likely to receive testosterone 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.

Source
 
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Nelson Vergel

Founder, ExcelMale.com
Warburton D, Hobaugh C, Wang G, Lin H, Wang R.

Testosterone replacement therapy and the risk of prostate cancer.

Asian J Androl.


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.

In the United States circumstance, it has become common for specialized outpatient clinics staffed by either urologists or other men's health-related fields to promote the concept of a "Low T Center." Such centers use direct-to-patient advertising methods to encourage self-referral for symptoms of fatigue, low libido, and other symptoms relevant. Consequently, those of us on the prostate cancer screening, detection, and treatment side of the equation encounter an increasing number of patients whose presentation started with an evaluation by a "Low T Center" that led to the detection of an elevated PSA either at baseline, or downstream of initiating testosterone replacement. Therefore, prostate cancer clinicians are increasingly having to factor in TRT into the management of men with elevated PSA and negative biopsy, as well as men treated for prostate cancer. It is common for TRT to be discontinued at the finding of an elevated PSA and certainly at the diagnosis of prostate cancer. If the TRT was working, they will likely want your opinion as to the safety of re-starting it at some point. Warburton et al. give us a state-of-the-art highlight of the common situations. At this point, the evidence is strongest that men with elevated PSA and negative biopsy, and post-RP with favorable pathology can re-start, and more data are needed for radiation patients and active surveillance."
TRT after prostate radiation.jpg
TRT after prostatectomy.jpg
TRT after prostatectomy.jpg
 
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Nelson Vergel

Founder, ExcelMale.com
Regis L, Planas J, Celma A, de Torres IM, Ferrer R, et al.

Behavior of total and free serum testosterone as a predictor for the risk of prostate cancer and its aggressiveness.
Actas Urol Esp.



CONTEXT: Serum testosterone is mostly bound to the sex hormone-binding globulin and albumin. A small metabolically active part is present in the form of free testosterone (FT). The relationship between serum total testosterone (TT) levels and prostate carcinogenesis is debated. Our hypothesis is that the serum FT concentration is more closely associated with the risk of prostate cancer (PC) and its aggressiveness than TT.

OBJECTIVE: To analyze the scientific evidence that relates serum TT and/or FT levels with the diagnosis of PC and its aggressiveness.

ACQUISITION OF EVIDENCE: A systematic review was conducted in PubMed up to January 2015 using the following mesh terms: prostate cancer, sex hormone, androgen, testosterone and free testosterone.

SYNTHESIS OF THE EVIDENCE: We found 460 publications, 124 of which were reviewed to analyze the evidence. The relationship between serum TT levels and the diagnosis of PC and its aggressiveness is highly heterogeneous. The variability in the design of the studies, the quantification methods and other variables could explain this heterogeneity. In a number of studies that evaluated the estimated or measured FT, the evidence remains equally conflicting.

CONCLUSIONS: Based on the current evidence, we cannot recommend the measurement of serum TT and/or TL levels for the diagnosis of PC or for assessing its aggressiveness.
 

Nelson Vergel

Founder, ExcelMale.com

Current Opinion on the Role of Testosterone in the Development of Prostate Cancer: A Dynamic Model
Posted: 30 Oct 2015 09:08 AM PDT



A Hypothetical Model Illustrates The Role Of Age-Related Declines In Testosterone (T) In The Development Of Pca


Two key components are included in our dynamic model: the magnitude of the age-related declines in testosterone and the individual-based threshold level of testosterone to maintain the normal function of prostate gland.


Our model emphasizes that the absolute value of testosterone measured at a single point is not indicative of PCa risk. Instead, the magnitude of the age-related declines in testosterone is a key factor.


The risk of PCa increases when testosterone levels fall below a threshold. As testosterone level falls below the threshold, prostatic cells reach the limit of their compensatory capabilities, thus impairing adaption to lower levels of testosterone and finally triggering the prostatic carcinogenesis process


Xu X, Chen X, Hu H, Dailey AB, Taylor BD. Current opinion on the role of testosterone in the development of prostate cancer: a dynamic model. BMC Cancer 2015;15(1):806. http://www.biomedcentral.com/1471-2407/15/806

BACKGROUND: Since the landmark study conducted by Huggins and Hodges in 1941, a failure to distinguish between the role of testosterone in prostate cancer development and progression has led to the prevailing opinion that high levels of testosterone increase the risk of prostate cancer. To date, this claim remains unproven.

PRESENTATION OF THE HYPOTHESIS: We present a novel dynamic mode of the relationship between testosterone and prostate cancer by hypothesizing that the magnitude of age-related declines in testosterone, rather than a static level of testosterone measured at a single point, may trigger and promote the development of prostate cancer.

TESTING THE HYPOTHESIS: Although not easily testable currently, prospective cohort studies with population-representative samples and repeated measurements of testosterone or retrospective cohorts with stored blood samples from different ages are warranted in future to test the hypothesis.

IMPLICATIONS OF THE HYPOTHESIS: Our dynamic model can satisfactorily explain the observed age patterns of prostate cancer incidence, the apparent conflicts in epidemiological findings on testosterone and risk of prostate cancer, racial disparities in prostate cancer incidence, risk factors associated with prostate cancer, and the role of testosterone in prostate cancer progression. Our dynamic model may also have implications for testosterone replacement therapy.

 
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Nelson Vergel

Founder, ExcelMale.com
Schenk JM, Till C, Hsing AW, et al.

Serum androgens and prostate cancer risk: results from the placebo arm of the Prostate Cancer Prevention Trial. Cancer Causes Control.

https://link.springer.com/article/10.1007/s10552-015-0695-0

BACKGROUND: Compelling and long-standing data suggest that androgens play an important role in the development of both normal prostate epithelium and prostate cancer. Although testosterone administration can induce prostate cancer (PCA) in laboratory animals, serum-based epidemiologic studies examining androgens in humans have not consistently supported a role for androgens in prostate carcinogenesis. We examined whether pre-diagnostic serum androgens were associated with PCA risk in the placebo arm of the Prostate Cancer Prevention Trial.

METHODS: In this nested case-control study, cases (n = 1,032) were primarily local-stage, biopsy-detected cancers, and controls (n = 1,025) were biopsy-confirmed to be PCA-free. Pre-diagnostic serum androgens (total testosterone, 3alpha-androstanediol glucuronide, free testosterone), estrogen-to-testosterone ratio, and sex hormone-binding globulin (SHBG) concentrations were measured in pooled (baseline and year 3) blood samples.

RESULTS: We found no significant associations between serum androgens, estrogen-to-testosterone ratios, or SHBG and risk of total, low (Gleason <7) or high-grade (Gleason 7-10) PCA.

CONCLUSION: Much remains to be learned about the role of androgens in prostate carcinogenesis. Further research is needed to evaluate the role of androgens, timing of exposure, genetic modulators of androgen metabolism, or environmental exposures that may affect androgen influence on prostate carcinogenesis.
 
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Nelson Vergel

Founder, ExcelMale.com
testosterone undecanoate injections (TU) for up to 8 years and 296 untreated hypogonadal controls.Journal of Clinical Oncology, 2016 Genitourinary Cancers Symposium (January 7-9, 2016).
Vol 34, No 2_suppl (January 10 Supplement), 2016: 50



Background: Testosterone therapy (TTh) in middle-aged and elderly men is still associated with concerns regarding prostate cancer (PCa). In this registry study, we investigated the incidence of PCa in hypogonadal patients on long-term treatment with TU in comparison to an untreated hypogonadal control group (CTRL).

Methods: In a cumulative registry study, 360 men (mean age: 57.37±7.29 years, range: 33-70) with testosterone (T) 12.1 nmol/L received TU 1000 mg every 12 weeks following an initial interval of 6 weeks for up to 8 years. 296 hypogonadal men (mean age: 64.79±4.28 years, range: 57-74) decided against TTh, mainly due to financial reasons. Prostate volume (PV) and PSA were measured and digital rectal examination (DRE)/ transrectal ultrasound (TRUS) performed before treatment initiation and then regularly every 3-6 months. Biopsies were performed when indicated according to EAU guidelines.

Results: From baseline to 8 years, PV increased from 29.24±10.38 to 31.13±11.45 ml in the T group and remained stable from 34.45±5.89 to 33.51±12 in CTRL. PSA increased slightly from 1.74 ± 0.93 to 1.83±0.93 ng/ml in the T group and remained stable from 2.25±1.34 to 2.19±1.17 in CTRL. In T-treated patients, 7 men (1.9%) were diagnosed with PCa. In the control group, 12 (4.1%) were diagnosed with PCa. The incidence per 10,000 years was 30.05 in the T group and 63.54 in CTRL. The mean age of PCa patients was 64 years in the T group and 65 years in CTRL. All patients underwent radical prostatectomy. The predominant Gleason score was 3 in all patients in the T group, lymph nodes and surgical margins were negative. In CTRL, three men had a predominant Gleason score of 3, 8 had 4, and 1 had 5. 7 patients had positive lymph nodes and no patient had a positive surgical margin.


Conclusions: Long-term treatment with TU in hypogonadal men undergoing regular monitoring according to EAU guidelines does not increase the incidence of PCa in comparison to an untreated hypogonadal CTRL group. PCa was more severe in the CTRL group.
 

Nelson Vergel

Founder, ExcelMale.com
From ENDO Conference 2016
Does Adequate Testosterone Therapy Protect Against Prostate Cancer? Incidence and Severity of Prostate Cancer in Patients Undergoing Prostate Biopsy in an Urological Office

Program: Abstracts - Orals, Poster Previews, and Posters
Session: SAT 134-160-Male Reproductive Endocrinology and Male Reproductive Tract (posters)
Bench to Bedside

Saturday, April 2, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board SAT 157


Background: There are still concerns regarding testosterone therapy (TTh) in middle-aged and elderly men and prostate cancer (PCa).
Methods: Between 2008 and July 2013, 553 prostate biopsies were performed in our office. 22 patients refused biopsy. We investigated incidence and severity of PCa in three groups: hypogonadal (T less than 350 ng/dl) men receiving TTh, hypogonadal untreated, and eugonadal men. All groups underwent similar screening intensity of at least once per year. Biopsies were performed when indicated according to EAU guidelines.
Results: In 42 hypogonadal men receiving TTh, 7 (16.7%) had a positive biopsy. Of these, 5 had a Gleason score &#8804;6 (71.4%) and 2 a Gleason score >6 (28.6%). Predominant Gleason score was 3 in all 7 men (100%). Tumor grade was II in 6 (85.7%) and II-III in 1 (14.3%) men.
In 162 untreated hypogonadal men, 84 (51.9%) had a positive biopsy. Of these, 34 had a Gleason score 6 (40.5%) and 50 a Gleason score >6 (59.5%). Predominant Gleason score was 3 in 65 (77.4%), 4 in 17 (20.2%) and 5 in 2 (2.4%) men. Tumor grade was II in 35 (41.7%), II-III in 10 (11.9%), III in 34 (40.5%) and IV in 5 (6.0%) men.
In 349 eugonadal men, 132 (37.8%) had a positive biopsy. Of these, 56 had a Gleason score &#8804;6 (42.4%) and 76 a Gleason score >6 (57.6%). Predominant Gleason score was 3 in 109 (82.6%), 4 in 22 (16.7%) and 5 in 1 (0.1%) men. Tumor grade was II in 59 (44.7%), II-III in 6 (4.5%), III in 63 (47.7%) and IV in 4 (3.0%) men.
Conclusions: The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TTh. The severity of PCa was significantly lower in hypogonadal patients receiving TTh. TTh may protect against high-grade PCa.
 

Nelson Vergel

Founder, ExcelMale.com
Is There A Protective Role Of Testosterone Against High-Grade Prostate Cancer?


This study investigated the role of testosterone replacement therapy (TRT) in prostate safety and cancer progression.
A cohort of 553 patients, 42 treated and 162 untreated hypogonadal men, and 349 eugonadal men were included.
Pathological analysis of prostate biopsies examining the incidence and severity of PCa revealed that:
• 16.7% of treated hypogonadal men had a positive biopsy, a Gleason score of </=6 in 71.4% and >6 in 28.6% of men, a predominant score of 3 and tumour staging of II in 85.7% men;
• 51.9% of untreated hypogonadal men had a positive biopsy, a Gleason score of </=6 in 40.5% and >6 in 59.5% men, a predominant score of 3 (77.4%) and tumour staging of II (41.7%) or III (40.5%);
• 37.8% of eugonadal men had a positive biopsy, a Gleason score of </=6 in 42.4% and >6 in 57.6% of men, a predominant score of 3 (82.6%) and tumour staging of II (44.7%) or III (47.7%).
The incidence of positive prostate biopsies was lowest in hypogonadal men receiving TRT, with significantly lower severity of PCa in terms of staging and grading in the same group.


These results suggest that TRT might have a protective effect against high-grade PCa.


Yassin A, Salman M, Talib RA, Yassin DJ. Is there a protective role of testosterone against high-grade prostate cancer? Incidence and severity of prostate cancer in 553 patients who underwent prostate biopsy: a prospective data register. Aging Male.

https://www.tandfonline.com/doi/abs/10.1080/13685538.2017.1298584?journalCode=itam20&
 
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Nelson Vergel

Founder, ExcelMale.com
Review Article

Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk?

David S. Lopez1,2, Shailesh Advani1, Konstantinos K. Tsilidis3,4, Run Wang2, Steven Canfield2

1Department of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center, School of Public Health, Houston, TX, USA; 2Division of Urology, The University of Texas Health Science Center, McGovern Medical School, Houston, TX, USA; 3Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; 4Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK

Abstract: For more than 70 years, the contention that high levels of testosterone or that the use of testosterone therapy (TTh) increases the development and progression of prostate cancer (PCa) has been widely accepted and practiced. Yet, the increasing and emerging evidence on testosterone research seems to challenge that contention. To review literature on the associations of endogenous and exogenous testosterone with decreased-, increased-, or null-risk of PCa, and to further evaluate only those studies that reported magnitude of associations from multivariable modeling as it minimizes confounding effects. We conducted a literature search to identify studies that investigated the association of endogenous total testosterone [continuous (per 1 unit increment and 5 nmol/L increment) and categorical (high vs. low)] and use of TTh with PCa events [1990&#8211;2016]. Emphasis was given to studies/analyses that reported magnitude of associations [odds ratio (OR), relative risk (RR) and hazard ratios (HRs)] from multivariable analyses to determine risk of PCa and their statistical significance. Most identified studies/analyses included observational and randomized placebo-controlled trials. This review was organized in three parts: (I) association of endogenous total testosterone (per 1 unit increment and 5 nmol/L increment) with PCa; (II) relationship of endogenous total testosterone (categorical high vs. low) with PCa; and (III) association of use of TTh with PCa in meta-analyses of randomized placebo-controlled trials. The first part included 31 observational studies [20 prospective (per 5 nmol/L increment) and 11 prospective and retrospective cohort studies (per 1 unit increment)]. None of the 20 prospective studies found a significant association between total testosterone (5 nmol/L increment) and increased- or decreased-risk of PCa. Two out of the 11 studies/analyses showed a significant decreased-risk of PCa for total testosterone per 1 unit increment, but also two other studies showed a significant increased-risk of PCa. Remaining studies reported null-risks values. Second part: eight of out of 25 studies reported an increased-risk of PCa for men with high levels of testosterone compared to low, but only four were statistically significant. However, 17 studies showed a decreased-risk of PCa after comparing high vs. low levels of testosterone, but 11 studies/analyses were statistically significant. Third part: two meta-analyses of randomized placebo-controlled trials (n=8 and n=11, each) that investigated use of TTh with PCa reported not significant decreased-risks of PCa. The contention that high levels of testosterone or that the use of TTh increases the risk of PCa doesn't seem to be supported from the literature. Yet, we still need a study with the adequate power, follow-up data, epidemiological, pathological and clinical data that can support the safety and beneficial effects of high levels of endogenous testosterone or use of TTh in the natural history of PCa and in men's health.

Keywords: Testosterone; treatment; endogenous; prostate; associations

FULL PAPER HERE
 
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