Low serum total testosterone & active surveillance

New study below [1].

"Low serum testosterone levels (<300 ng/dL) were significantly associated with upgrading, upstaging, unfavorable disease and positive surgical margins. The addition of testosterone to a base model, including age, PSA, PSA density, clinical stage and positive cancer involvement in cores, showed a significant independent influence of this variable on upstaging, upgrading and unfavorable disease.In conclusion, our results support the idea that total testosterone should be a selection criterion for inclusion of low-risk PCa patients in AS programs and suggest that testosterone level less than 300 ng/dL should be considered a discouraging factor ..."

Perhaps not a subject for this group, but in none of the papers dealing with low T & poorer prognosis, has there ever been a suggestion that treatment with T might improve a man's prospects. & there seems to be no curiosity as to why the cancer does better when T is low.

...

Earlier this year there was an Italian study that found that [PSA/free T]:

"directly associates with aggressive features of pathology PCA; moreover, it might express prognostic potential for clustering the patient population in risk classes."

While free T correlates to total T at the group level, individuals vary. Free T might have been a better choice in [1].

...

Another new study [3]:

"https://www.ncbi.nlm.nih.gov/pubmed/27792861"

No mention of PCa in the free text, but PubMed returns it as a PCa hit.

The big mystery is why diabetics get less PCa - they get more of everything else. My take on this is that PCa risk is higher when insulin levels are higher. Pre-diabetics have high insulin levels; diabetics have burned-out beta cells & insulin levels have fallen (not the best way of dealing with PCa risk). The metabolic syndrome [MetS] is a PCa risk factor, & there is a great overlap between MetS & pre-diabetes. i.e. diabetics do not really have reduced risk - pre-diabetics have increased PCa risk.

So what happens to hormones in the pre-diabetic?

"... total testosterone concentration was lower among men with ... than without ... pre-diabetes."

"After adjusting for demographic and lifestyle factors, pre-diabetic men had a higher odds of lower testosterone (OR: 2.58 ...), higher free estradiol {E2} level (OR: 1.59 ...), and lower SHBG level (OR: 2.27 ...) compared to men without pre-diabetes."

Lower T & higher E2. T & E2 tend to move in tandem in opposite directions. I'm inclined to think that the ratio might have prognostic value when assessing risk for PCa. Unfortunately, the ratio cannot self correct. Elevated E2 is a cause of T reduction. With lower T we get increased visceral adiposity - & those fat cells secrete E2. T replacment can reverse that.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/277...

Oncotarget. 2016 Oct 25. doi: 10.18632/oncotarget.12906. [Epub ahead of print]

Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance.

Ferro M1, Lucarelli G2, Bruzzese D3, Di Lorenzo G4, Perdonà S5, Autorino R6, Cantiello F7, La Rocca R8, Busetto GM9, Cimmino A10, Buonerba C4, Battaglia M2, Damiano R7, De Cobelli O1,11,12, Mirone V8, Terracciano D13.

Author information

Abstract

Active surveillance (AS) is currently a widely accepted treatment option for men with clinically localized prostate cancer (PCa). Several reports have highlighted the association of low serum testosterone levels with high-grade, high-stage PCa. However, the impact of serum testosterone as a predictor of progression in men with low-risk PCa has been little assessed.In this study, we evaluated the association of circulating testosterone concentrations with a staging/grading reclassification in a cohort of low-risk PCa patients meeting the inclusion criteria for the AS protocol but opting for radical prostatectomy.Radical prostatectomy (RP) was performed in 338 patients, eligible for AS according to the following criteria: clinical stage T2a or less, PSA<10ng/ml, two or fewer cancer cores, Gleason score (GS)≤6 and PSA density<0.2 ng/mL/cc. Reclassification was defined as upstaging (stage>pT2) and upgrading (GS≥7; primary Gleason pattern 4) disease. Unfavorable disease was defined as the occurrence of pathological stage>pT2 and predominant Gleason score 4. Total testosterone was measured before surgery.Low serum testosterone levels (<300 ng/dL) were significantly associated with upgrading, upstaging, unfavorable disease and positive surgical margins. The addition of testosterone to a base model, including age, PSA, PSA density, clinical stage and positive cancer involvement in cores, showed a significant independent influence of this variable on upstaging, upgrading and unfavorable disease.In conclusion, our results support the idea that total testosterone should be a selection criterion for inclusion of low-risk PCa patients in AS programs and suggest that testosterone level less than 300 ng/dL should be considered a discouraging factor when a close AS program is considered as treatment option.

KEYWORDS:

active surveillance; prostate cancer; testosterone; upgrading; upstaging

PMID: 27793023 DOI: 10.18632/oncotarget.12906

[PubMed - as supplied by publisher]

...

[2] Full text: pagepressjournals.org/index...

Abstract:

ncbi.nlm.nih.gov/pubmed/270...

Arch Ital Urol Androl. 2016 Mar 31;88(1):17-22. doi: 10.4081/aiua.2016.1.17.

The preoperative serum ratio of total prostate specific antigen (PSA) to free testosterone (FT), PSA/FT index ratio, and prostate cancer. Results in 220 patients undergoing radical prostatectomy.

Porcaro AB1, Caruso B, Terrin A, De Luyk N, Cacciamani G, Corsi P, Inverardi D, De Marchi D, Baldassarre R, Cerruto M, Ghimenton C, Brunelli M, Zecchini Antoniolli S, Petrozziello A, Artibani W.

Author information

Abstract

OBJECTIVES:

To evaluate associations of preoperative total prostate specific antigen (PSA) to free testosterone (FT), the PSA/FT index ratio, with features of pathology prostate cancer (PCA) and to investigate its prognostic potential in clustering the PCA population.

PATIENTS AND METHODS:

After excluding criteria, the records of 220 patients who underwent radical prostatectomy (RP) were retrospectively reviewed. Serum samples of PSA, total testosterone (TT) and FT were collected at 8.00 A.M., one month after biopsies and before RP. The PSA/FT ratio was computed in the population of patients who were clustered in groups according to ranking intervals of the PSA/FT ratio which identified at least 4 clusters which were coded as A, B, C, and D. The independent associations of the PSA/FT index ratio were assessed by statistical methods and a two-sided P &lt; 0.05 was considered to indicate statistical significance.

RESULTS:

TT correlated to FT which was a significant predictor of PSA in the population of patients who were subsequently clustered, according to increasing interval values of the PSA/FT index ratio, in groups that showed a stronger linear association of FT with PSA. The PSA/FT index ratio significantly associated with pathology features of prostate cancer such as pathology Gleason score (pGS), invasion of the seminal vesicles (pT3b), proportion of positive cores (P+) and proportion of cancer involving the volume of the prostate. In the population of patients, TT, PSA/FT index ratio and P+ independently associated with pGS ≥ 7 and pT3b; moreover, the odds ratio (OR) of the PSA/FT index ratio resulted 9.11 which was stronger than TT (OR = 1.11) and P+ (OR = 8.84). In the PCA population, TT, PSA/FT index ratio and P+ also independently associated with pT3b PCA; interestingly, the OR of PSA/FT index resulted 54.91 which was stronger than TT (OR = 1.31) and P+ (26.43).

CONCLUSIONS:

Preoperative PSA/FT index ratio is an independent strong factor which directly associates with aggressive features of pathology PCA; moreover, it might express prognostic potential for clustering the patient population in risk classes. Confirmatory studies are required.

PMID: 27072171 DOI: 10.4081/aiua.2016.1.17

[PubMed - indexed for MEDLINE]

...

[3] ncbi.nlm.nih.gov/pubmed/277...

Andrology. 2016 Oct 28. doi: 10.1111/andr.12287. [Epub ahead of print]

Pre-diabetes and serum sex steroid hormones among US men.

Arthur R1, Rohrmann S2, Møller H3, Selvin E4, Dobs AS5,6, Kanarek N7,6, Nelson W6, Platz EA4,6, Van Hemelrijck M3,8.

Author information

1King's College London, Division of Cancer Studies, Cancer Epidemiology Group, London, UK. rhonda.arthur@kcl.ac.uk.

2Department of Chronic Disease Epidemiology; Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich, Zurich, Switzerland.

3King's College London, Division of Cancer Studies, Cancer Epidemiology Group, London, UK.

4Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

5Department of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

6Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.

7Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

8Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Abstract

Several studies demonstrate a link between diabetes and sex steroid hormones, but the link with pre-diabetes remains elusive. In this study, we hypothesize that pre-diabetes, which is characterised by having impaired fasting glucose and/or impaired glucose tolerance and/or impaired HbA1C, may influence circulating sex steroid hormone concentrations in men. Thus, we investigated whether serum sex steroid hormone concentrations differ between men with and without pre-diabetes. We analyzed data for 1139 men who were aged 20+ years when they participated in the Third National Health and Nutrition Examination Survey. We calculated adjusted geometric mean serum concentrations of total and estimated free testosterone, androstanediol glucuronide, total and estimated free estradiol, and sex hormone-binding globulin (SHBG) in men with and without pre-diabetes. Logistic regression was used to calculate adjusted odds ratios (OR) of lower concentrations of androgens and SHBG, and higher concentrations of estradiol by prediabetes status. Adjusting for age and race/ethnicity, total testosterone concentration was lower among men with (geometric mean: 4.68 ng/mL) than without (5.36 ng/mL, p = 0.01) pre-diabetes. SHBG concentration was also lower in men with (31.67 nmol/L) than without (36.16 nmol/L; p = 0.01) pre-diabetes. Concentrations of the other hormones did not differ between men with and without pre-diabetes. After adjusting for demographic and lifestyle factors, pre-diabetic men had a higher odds of lower testosterone (OR: 2.58; 95% CI: 1.54-4.29), higher free estradiol level (OR: 1.59; 95% CI: 1.14-2.22), and lower SHBG level (OR: 2.27; 95% CI: 1.32-3.92) compared to men without pre-diabetes. These associations were attenuated after adjusting for adiposity (testosterone OR: 1.76; 95% CI 0.95-3.27, free estradiol OR: 1.29, 95% CI: 0.88-1.88, SHBG OR: 1.71; 95% CI 0.88-3.30). Our findings suggest that men with pre-diabetes have lower circulating total testosterone and SHBG and higher free estradiol levels.

© 2016 American Society of Andrology and European Academy of Andrology.

KEYWORDS:

NHANES; prostate cancer; sex steroid hormones

PMID: 27792861 DOI: 10.1111/andr.12287

[PubMed - as supplied by publisher]

1 Reply

oldestnewest
  • Important report...thanks.

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