PCa & low levels of serum testosterone

New study below.

"A total of 605 PrCa patients ... underwent robotic-assisted radical prostatectomy between September 2010 and January 2013 at the University of Pennsylvania ..."

"Androgen deficiency was determined as serum free testosterone (FT) <47 pg/ml and total testosterone (TT) <193 ng/dl."

A few comments:

- hypogonadism is often defined as TT <350 ng/dL. I wish they had also reported on men in the 193-350 ng/dL range.

- the 193 ng/dL cut-off number must have a rationale. I wonder what it was.

- men below 193 ng/dL were not considered deficient if FT was 47 pg/mL or higher. This is quite a stringent definition of deficiency.

- in looking at men with such low TT & FT they might have come across men who were at castrate or near castrate levels. I have been hypothesizing that an unfavorable TT:estradiol ratio can lead to aggressive PCa. However, estradiol needs some testosterone to be present, for proliferation.

- men who were not deficient were classed as "normal", which is really stretching the definition of normal.

Anyway:

"Among middle-aged men (45-64 years; n = 367), those with low FT and low TT had, on average, a higher BMI (29.7 vs. 27.4 ... and 32.2 vs. 27.6 ... respectively) and higher proportion of Gleason 8-10 PrCa (13.3% vs. 4.8% ... and 19.2% vs. 5.1% ...) compared to men with normal FT and normal TT values. Patients with low FT had also higher number of positive cores on biopsy (3.9 vs. 3.1 ...) and greater tumor volume (7.9 ml vs. 6.1 ml ...) compared to those with normal FT."

"Among men aged 45-64 years low serum pretreatment FT and TT predicted more aggressive features of PrCa in prostatectomy specimens. In middle-aged patients low testosterone levels measured pre-operatively may indicate more aggressive disease parameters."

High BMI usually correlates with high estradiol [E2]. I wish someone would look at the E2:TT ratio in such studies.

Oddly: "Among men ≥65 years (n = 135) there was no difference in prostatectomy specimens of PrCa between patients with low or normal FT or TT."

In 1982, Zumoff [2] suggested that PCa might be two diseases:

"The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal. The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a "two-disease" theory of prostate cancer, with possible differences in genetic factors and prognosis."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/283...

Prostate Int. 2017 Mar;5(1):17-23. doi: 10.1016/j.prnil.2016.12.003. Epub 2017 Jan 12.

Low levels of serum testosterone in middle-aged men impact pathological features of prostate cancer.

Llukani E1, Katz BF2, Agalliu I3, Lightfoot A2, Yu SS2, Kathrins M2, Lee Z4, Su YK2, Monahan Agnew K2, McGill A2, Eun DD4, Lee DI2.

Author information

1

Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Urology, New York University School of Medicine, New York, NY, USA.

2

Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

3

Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA; Department of Urology, Albert Einstein College of Medicine, New York, NY, USA.

4

Department of Urology, Temple University Health System, Philadelphia, PA, USA.

Abstract

BACKGROUND:

Serum testosterone deficiency increases with aging. Age is also a major risk factor for prostate cancer (PrCa) and PCa tumors are more frequently diagnosed among men >65 years old. We evaluated the relationship between preoperative serum testosterone and clinical/ pathological features of PrCa in middle-aged and elderly patients.

METHODS:

A total of 605 PrCa patients who underwent robotic-assisted radical prostatectomy between September 2010 and January 2013 at the University of Pennsylvania, and who had serum testosterone levels measured using Elecsys Testosterone II Immunoassay were included in this IRB-approved protocol. Androgen deficiency was determined as serum free testosterone (FT) <47 pg/ml and total testosterone (TT) <193 ng/dl. Demographic, clinical and tumor characteristics of men with low vs. normal TT or FT were compared using t-test or chi-square tests. Logistic regression was used to determine associations of clinical and pathological variables with FT or TT levels.

RESULTS:

Among middle-aged men (45-64 years; n = 367), those with low FT and low TT had, on average, a higher BMI (29.7 vs. 27.4, P < 0.01; and 32.2 vs. 27.6; P < 0.01, respectively) and higher proportion of Gleason 8-10 PrCa (13.3% vs. 4.8%, P = 0.011; and 19.2% vs. 5.1%, P = 0.012) compared to men with normal FT and normal TT values. Patients with low FT had also higher number of positive cores on biopsy (3.9 vs. 3.1 P = 0.019) and greater tumor volume (7.9 ml vs. 6.1 ml, P = 0.045) compared to those with normal FT. Among men ≥65 years (n = 135) there was no difference in prostatectomy specimens of PrCa between patients with low or normal FT or TT.

CONCLUSION:

Among men aged 45-64 years low serum pretreatment FT and TT predicted more aggressive features of PrCa in prostatectomy specimens. In middle-aged patients low testosterone levels measured pre-operatively may indicate more aggressive disease parameters.

KEYWORDS:

Gleason score; Localized prostate cancer; Middle age; Robotic-assisted laparoscopic prostatectomy; Testosterone

PMID: 28352619 PMCID: PMC5357970 DOI: 10.1016/j.prnil.2016.12.003

[2] ncbi.nlm.nih.gov/pubmed/715...

Prostate. 1982;3(6):579-88.

Abnormal levels of plasma hormones in men with prostate cancer: evidence toward a "two-disease" theory.

Zumoff B, Levin J, Strain GW, Rosenfeld RS, O'Connor J, Freed SZ, Kream J, Whitmore WS, Fukushima DK, Hellman L.

Abstract

The 24-hr mean plasma concentrations of 13 hormones or hormone metabolites (cortisol, testosterone, dihydrotestosterone, dehydroisoandrosterone, dehydroisoandrosterone sulfate, androsterone, androsterone sulfate, estrone, thyroxine, triiodothyronine, LH, FSH, and prolactin) were measured in 16 rigorously screened patients (aged 55-80) with stage C or D prostate cancer and 36 normal men. Nine of the hormones showed no abnormalities in the patients but four (testosterone, dihydrotestosterone, cortisol, and estrone) showed abnormalities. Testosterone and dihydrotestosterone, which, respectively, decreased with age and showed no change with age in the normal men, rose sharply with age in the patients. The patients' curves crossed the normal curves at about age 65; patients 65 or above showed normal values while patients under age 65 showed significantly subnormal levels of both hormones: testosterone averaged 282 ng/dl in patients vs 434 ng/dl in controls (P less than 0.0001) and dihydrotestosterone averaged 70 ng/dl in patients vs 99 ng/dl in controls (P less than 0.01). Cortisol, which was age invariant in the normal men, fell sharply with age in the patients; patients under 65 had significantly elevated levels (10.1 vs 6.9 micrograms/dl; P less than 0.0001), while patients 65 or older had normal levels. Estrone levels were age invariant in both patients and controls, but the mean level in patients was markedly elevated (81 vs 47 pg/ml in controls; P less than 0.001). The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal. The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a "two-disease" theory of prostate cancer, with possible differences in genetic factors and prognosis.

PMID: 7155990

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