Low Free Testosterone and Prostate Cancer Risk.

[pjoshea13]

New study below.

"A Collaborative Analysis of 20 Prospective Studies" involving 45 researchers from 37 institutions. Many of the usual suspects.

"Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77 ...) compared with men with higher concentrations (2nd-10th tenths of the distribution)."

Note that the lowest decile would include men with insufficient testosterone [T] to meet the level needed for Morgentaler's saturation model, as well as men with T in the castrate range (effectively ADT). One might well expect protection against PCa for the latter.

However, while there was 24% less risk of low-grade disease, there was 56% more risk of high-grade disease.

"Further research is needed ..." LOL

Meanwhile, from the Patient Summary: "... men with low testosterone had a lower risk of prostate cancer." (Seems to be remarkably short on nuance.)

Most studies have looked at T rather than free-T. A number have reported more serious disease with low T. When T is in the hypogonadal range, one must distinguish cases at the low end, who are essentially on a form of ADT, from cases at the high end, where T is high enough to saturate the androgen receptors, but not high enough to fill its role as a regulator of prostate growth.

-Patrick

ncbi.nlm.nih.gov/pubmed/300...

Eur Urol. 2018 Aug 1. pii: S0302-2838(18)30546-3. doi: 10.1016/j.eururo.2018.07.024. [Epub ahead of print]

Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies.

Watts EL1, Appleby PN2, Perez-Cornago A2, Bueno-de-Mesquita HB3, Chan JM4, Chen C5, Cohn BA6, Cook MB7, Flicker L8, Freedman ND7, Giles GG9, Giovannucci E10, Gislefoss RE11, Hankey GJ12, Kaaks R13, Knekt P14, Kolonel LN15, Kubo T16, Le Marchand L15, Luben RN17, Luostarinen T18, Männistö S19, Metter EJ20, Mikami K21, Milne RL9, Ozasa K22, Platz EA23, Quirós JR24, Rissanen H14, Sawada N25, Stampfer M26, Stanczyk FZ27, Stattin P28, Tamakoshi A29, Tangen CM30, Thompson IM31, Tsilidis KK32, Tsugane S25, Ursin G33, Vatten L34, Weiss NS35, Yeap BB36, Allen NE37, Key TJ2, Travis RC2.

Author information

1

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. Electronic address: [e-mail].

2

Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

3

Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands; Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands; Department of Epidemiology and Biostatistics, Imperial College London, London, UK; Department of Social & Preventive Medicine, University of Malaya, Kuala Lumpur, Malaysia.

4

Department of Epidemiology and Biostatistics, University of California-San Francisco, San Francisco, CA, USA; Department of Urology, University of California-San Francisco, San Francisco, CA, USA.

5

Public Health Sciences Division, Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

6

Child Health and Development Studies, Public Health Institute, Berkeley, CA, USA.

7

Division of Cancer Epidemiology and Genetics, U.S. National Cancer Institute, Bethesda, MD, USA.

8

School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Western Australian Centre for Health and Ageing, Centre for Medical Research, University of Western Australia, Perth, Western Australia, Australia.

9

Cancer Epidemiology and Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.

10

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; The Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

11

Cancer Registry of Norway, Institute for Epidemiological Cancer Research, Oslo, Norway.

12

School of Medicine, University of Western Australia, Perth, Western Australia, Australia.

13

Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.

14

National Institute for Health and Welfare, Helsinki, Finland.

15

University of Hawaii Cancer Center, Honolulu, HI, USA.

16

Department of Preventive Medicine and Community Health, University of Occupational and Environmental Health, Kitakyushu, Japan.

17

Strangeways Research Laboratory, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

18

Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

19

Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland.

20

Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.

21

Department of Urology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.

22

Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.

23

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

24

Public Health Directorate, Asturias, Spain.

25

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

26

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; The Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

27

Division of Reproductive Endocrinology and Infertility, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

28

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

29

Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

30

SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

31

Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, TX, USA.

32

Department of Epidemiology and Biostatistics, Imperial College London, London, UK; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.

33

Cancer Registry of Norway, Institute for Epidemiological Cancer Research, Oslo, Norway; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.

34

Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

35

Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.

36

School of Medicine, University of Western Australia, Perth, Western Australia, Australia; Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia.

37

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Abstract

BACKGROUND:

Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.

OBJECTIVE:

To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.

DESIGN, SETTING, AND PARTICIPANTS:

Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.

RESULTS AND LIMITATIONS:

Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (phet=0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation.

CONCLUSIONS:

Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade.

PATIENT SUMMARY:

In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer.

Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Androgens; Epidemiology; Pooled analysis; Prospective studies; Prostate cancer; Sex hormones; Testosterone

PMID: 30077399 DOI: 10.1016/j.eururo.2018.07.024

[cesanon]

Patrick

What basically is the difference between testosterone and free testosterone?

[pjoshea13 in reply to cesanon]

Free-T is about 1-2% of total T. It's the number that matters IMO. The rest is bound to proteins - strongly bound to SHBG or weakly bound to albumin.

-Patrick

[curt504a]

Thanks!! Cherry picking sentences:

>> where T is high enough to saturate the androgen receptors, but not high enough to fill its role as a regulator of prostate growth.

I started anti-aging protocol of suplimenting my T with topical cream, blood test T and free T every few months, as soon as my T was dropping to the low range. I currently supplement into the mid to high range meaning probably typical for 45 yr old or younger, yet I'm much older.

Our bodies where designed for youthful hormone levels, I believe its in my best interests to never let them drop below mid range starting at what ever age you may be when your hormones started dropping. I've always done my own blood testing, lef.org / lifeextension.com, With out regard to BPH, PCA, the anti-aging Drs will start supplementing a man 45ish on up depending on T / TSH blood testing. This was about when I started topical T.

I had a 3T mp MRI 6 mo ago and the prostrate was clean and near normal sized. My leap to the MRI was on my PSA jumping from 0.5 to 6.5 in 6 mo. then back down to 2.5, now down to 1.5. Had a semin bacteria DNA test and a bunch of typical bugs where found but in high concentrations. Prostatis..

Tnx for this post, I'll hang onto the 1/2 a sentenance; but not high enough to fill its role as a regulator of prostate growth, and keep my T up mid range to high range on the keep it in youthful range argument... And now also "fill its role as a regulator of prostate growth".

Women have the same thing in play, meaning they have no brain, organ degradation if they never let estrogen drop, buy jumpping on BHRT early before many months below range go by.

Too bad no such book has been written on hypoandrogenism in middle life men, as this book is for women: The Estrogen Window...

amazon.com/gp/product/16233...

My wife found this book (in tandem to alot of other study) to be key to her staying on BHRT and blood testing.

The study re estrogen and women finds: if you wait too long, your estrogen has been low, near zero for greater then 1-2 years (post menopause), the benefit of BHRT in reducing breast cancer risk is lost.... The women needs to detect low E early and BHRT early and keep it up.

Translating to men, I've read no studies about the lack of value or danger of jumpping near zero T in a man who';s been low for some time, back up to normal or even high range with supplimentation??? We need this data. My guess is that the body shuts down important functions (sex function etc etc,) when T drops and stays low that the body won't spring back with newly added T (and other hormones, T4/T3, DHEA etc). Just my guessing, that the body would function better if we never let T etc drop in the first place...

Its shocking what standard of care has no clue about!!!!!! We need more studies. In absence to studies we have these groups, face book self study groups etc.

[arete1105]

Patrick- you are going to have to help me here understand this study. If you have low free T, that means you have not reached the Saturation Level for T. Correct? It seems this study implies that men with low T and low free T have a better chance of not getting prostate cancer. So the inverse would seem to be true also. So then why in early age, 20-30, when men have the highest T and probable the highest free T isn't there an epidemic of prostate cancer? Prostate cancer seems to correlate with low T, older men.

[pjoshea13 in reply to arete1105]

Older men have lower T. We lose 1-2% every year from our early 30's.

Many men, when diagnosed, are near the cut-off for hypogonadism (350 ng/dL).

At the top of the 0-350 range, there is enough T to permit growth, but not enought to resist proliferation.

At the bottom, we get into ADT territory (protection).

So we have the paradox that the hypogonadal range is associated with, both, an increase & a decrease in risk.

The hypogonadal range needs to be broken up into two ranges.

-Patrick

[arete1105 in reply to pjoshea13]

Patrick- another question: what is the functional difference between T bound to SHBG, Albumin and Free T?

[pjoshea13 in reply to arete1105]

SHBG-T is considered to be bio-unavailable.

Albumin-T can become bioavailable because the bond is weak.

Free-T is ready for action.

-Patrick