Testosterone.

[pjoshea13]

New German-U.S. paper below [1].

Somewhat off-topic, but I know that a lot of men still regard testosterone [T] as PCa "fuel". It's not surprising. I was born at the start of the Huggins era & I'm astonished that we are still living in it. Huggins basically got his Nobel Prize for discovering that castration could be used to treat PCa. Giving the impression that T is dangerous stuff. {Well, T is a pussycat compared to estradiol [E2] - women reading this, feel free to chime in. LOL}

However, young men with high-normal T do not get PCa. When men do get PCa, T levels are typically significantly lower (the decline begins in one's early 30's at a rate of 1-2% / year). Men with PCa who have the lowest T at diagnosis have the worst prognosis. And T deprivation is merely palliative - not a cure - & fails within 18 to 24 months for most men.

Thanks to Dr. Morgentaler, the attitude towards T is changing. Doctors have been wary of treating hypogonadism in older men, for fear of unmasing occult PCa. That fear seems unfounded - certainly on a group basis.

The new study followed 805 hypogonadal men for up to 12 years. 412 "underwent TTh {long-term testosterone therapy with testosterone undecanoate}, 393 patients served as controls"

"TTh led to substantial and sustained reduction of ED; improvement in erectile function was significant for each successive year until year 9. This was accompanied by improvements in cardiometabolic risk factors and urinary function throughout the 12-year follow-up period. Benefits of TTh were stronger for patients with moderate/severe ED than for patients with no/minor ED. Incidence of prostate cancer, major adverse cardiovascular events, and mortality were significantly lower in men on TTh compared with untreated men."

"Long-term TTh for up to 12 years alleviates ED, improves cardiometabolic risk factors, and reduces prostate cancer. Patients must stay on TTh consistently for a long time to achieve maximum benefits of TTh."

It's not the first study to show that PCa risk can be reduced by restoring T levels.

My attitude to T was formed years ago when I looked at studies of the androgen receptor [AR]. At diagnosis, the AR is rarely mutated, but is invariably so by the time that ADT fails. In contrast, estogen receptor [ER] changes occur quite early (before diagnosis), with growth-inhibting ERbeta disappearing & growth-promoting ER-alpha taking its place. But researchers seem not to be interested in the role of estradiol in PCa.

We have seen two PCa prevention trials that sought to protect men by lowering dihydrotestosterone [DHT] levels: (1) the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial & (2) the {Finasteride} Prostate Cancer Prevention Trial (PCPT). Too bad that there will never be funding for a PCa prevention trial based on T restoration.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/307...

Aging Male. 2019 Feb 20:1-12. doi: 10.1080/13685538.2019.1575354. [Epub ahead of print]

Long-term treatment with testosterone undecanoate injections in men with hypogonadism alleviates erectile dysfunction and reduces risk of major adverse cardiovascular events, prostate cancer, and mortality.

Saad F1, Caliber M2, Doros G3, Haider KS4, Haider A4.

Author information

1

a Medical Affairs Andrology , Bayer AG , Berlin , Germany.

2

b American Medical Writers Association , Ft Lauderdale , FL , USA.

3

c Department of Epidemiology and Statistics , Boston University School of Public Health , Boston , TX , USA.

4

d Private Urology Practice , Bremerhaven , Germany.

Abstract

OBJECTIVE:

The association between erectile dysfunction (ED), hypogonadism, cardiovascular disease, and type 2 diabetes is well documented, but long-term data are limited. The aim of this study is to investigate effects of long-term testosterone therapy (TTh) with testosterone undecanoate in men with hypogonadism and ED.

PATIENTS AND METHODS:

Observational, prospective registry of 805 hypogonadal men with different degrees of ED, evaluated by the International Index of Erectile Function - Erectile Function Domain. Four hundred and twelve patients underwent TTh, 393 patients served as controls, with an observation period up to 12 years.

RESULTS:

TTh led to substantial and sustained reduction of ED; improvement in erectile function was significant for each successive year until year 9. This was accompanied by improvements in cardiometabolic risk factors and urinary function throughout the 12-year follow-up period. Benefits of TTh were stronger for patients with moderate/severe ED than for patients with no/minor ED. Incidence of prostate cancer, major adverse cardiovascular events, and mortality were significantly lower in men on TTh compared with untreated men.

CONCLUSION:

Long-term TTh for up to 12 years alleviates ED, improves cardiometabolic risk factors, and reduces prostate cancer. Patients must stay on TTh consistently for a long time to achieve maximum benefits of TTh.

KEYWORDS:

Erectile dysfunction; cardiovascular disease; hypogonadism; prostate cancer; quality of life; testosterone therapy

PMID: 30782054 DOI: 10.1080/13685538.2019.1575354

[Dayatatime]

Anyone not familiar with Morgentaler should read his work. The fact that theories and treatment are basically the same since discovered in 1941 may answer the question as to why advanced prostate cancer is considered incurable. Perhaps research has been barking up the wrong tree for 80 years.

medicinacomplementar.com.br...

You may have to start video at the beginning:

youtu.be/6a0vvEh_GtE(Not working as expected?)

Ron

[jimreilly]

It seems these ideas (that low T can be treated without increased Prostate cancer risk) have been floating around for a little while now. Is there a change going on--i.e. are more doctors gradually accepting this? And the nay-sayers--what is their reasoning?

[jimbob99999]

Its a good video, but leaves me uncertain what to do now. The implication is that we will have the same life span regardless of whether we are on ADT or not, so why not just enjoy life?

[Break60]

If E2 is the villain why is it being used in lieu of Lupron or the like in the PATCH trial in the UK as ADT?

[pjoshea13 in reply to Break60]

It's all a matter of the E2 level.

1] E2 at very high doses cause gonadal T production to cease. E2 cannot stimulate PCa when T is at castrate levels.

2] E2 is a general health issue in men when levels go above 30 pg/mL.

At that level, T is often close to or below the hypogonadal cutoff of 350 ng/dL. Because of the common inverse relationship, a number of researchers find the E2:T ratio to be useful. A poor ratio (estrogen dominance) is implicated is cardiovascular problems & other issues. & this includes PCa, IMO.

3] If E2 is <12 pg/mL, there will be bone problems. Men on ADT with low E2 should use a low dose E2 patch.

-Patrick

[Break60]

I’m using (4) .1 mg Estradiol patches per week after stopping Lupron. Like the trial .

[pjoshea13 in reply to Break60]

I don't know the PATCH dose, but:

"After three months of treatment, 96% of men in each treatment arm had castration-level testosterone concentrations (no more than 1.7 nmol/L). Mean estradiol levels were 70 pmol/L in the LHRHa arm and 685 pmol/L in the estradiol arm." [1]

i.e. 19 pg/mL & 187 pg/mL, respectively.

Are you tracking T & E2?

-Patrick

[1] journalofclinicalpathways.c...

[Break60 in reply to pjoshea13]

Patrick

I had not been tracking E2 but I will for next blood test. I’ve only been on this estradiol patch regimen for a week.

[pjoshea13 in reply to Break60]

OK. Good luck with it. -Patrick

[cbgjr]

really interesting stuff. these are some thoughts that come to mind right away.

1) the ncbi link was from 2012 and it looks like this concept never gained any traction since then. why?

2) their observation that higher T results in less ED is like saying water is wet.

3) also: "Incidence of prostate cancer, major adverse cardiovascular events, and mortality were significantly lower in men on TTh compared with untreated men". The way I understood it, the "lower incidence of PCa" indicates that they were referring to men without the disease. no mention of the possible effects of increasing T (everything else being the same) on guys with already advanced PCa. My guess is that they would die sooner.

4) the video link submitted on another reply , ( Dr Morgentaler) was also very interesting, does any body know its date?

5) I think this whole thing seems to support the BAT treatment approach,,,

[Dayatatime in reply to cbgjr]

Published on Mar 31, 2016, Men's Health Boston.

[cbgjr in reply to Dayatatime]

thank you

[pjoshea13]

The study I posted was new (Feb 2019 - not 2012):

"Aging Male. 2019 Feb 20:1-12. doi: 10.1080/13685538.2019.1575354. [Epub ahead of print]"

But I doubt that anyone treating PCa patients has a subscription to "Aging Male" - or even has time to read the journals that they do receive.

It's a joint U.S.-German study. I wonder if the data is also joint or exclusively from one of the countries - could make a difference as to PSA screening status. Were the men screened before receiving T - & regularly thereafter?

Cbgir writes "no mention of the possible effects of increasing T ... on guys with already advanced PCa. My guess is that they would die sooner."

From the study - in the 12 year follow-up period:

"Incidence of prostate cancer ... and mortality were significantly lower in men on TTh compared with untreated men"

Of course, there might not have been many men who were advanced at diagnosis. (Which is why screening status interests me.)

{I clicked on the "Reply" to Cbgir, but is appears that I am replying to myself. Tried it twice.}

-Patrick

[cbgjr in reply to pjoshea13]

sorry, i read it wrong : Aging Male. 2019 Feb 20:1-12. doi: 10.1080/13685538.2019.1575354. [Epub ahead of print]

I thought it said Feb 2012 (!) it looks like in addition to PCa now I have dyslexia as well...

[Bob10]

I'm thinking of going on testosterone lots of it because I don't want to be castrated any more 0