Future PCa in younger men.

[pjoshea13]

This post is prompted by a new American Urological Association paper below [1].

"TRENDS IN SERUM TESTOSTERONE LEVELS AMONG ADOLESCENT AND YOUNG ADULT MEN IN THE UNITED STATES"

My generation of males had no fertility problems as I recall. Quite the reverse, in fact. A generation later & one hears "they are trying for a baby." I became interested in this when my son was 'trying'. Many, many papers out there on declining male fertility, & there seems to be no end to the decline.

Oddly, I don't recall anything on a parallel decline in testosterone [T].

The T value that seems to be used for hypogonadism these days is 350 ng/dL. Perhaps that 350 ng/dL limit is akin to the vitamin levels needed to prevent scurvy, rickets & beriberi - one would want to be a bit higher in the observed range.

With that 350 in mind, look at the graph in the link. The average T level in young men in 1999-2000 was close to 600 ng/dL. The decline seems to have already linear at this point. By 2015-16 it had fallen ~200 points. It may be alreay at the 350 mark.

Although increasing BMI explains much of that: "Even in men with normal BMI (18.5-24.9), TT levels have declined from 664.79 ng/dL to 529.24 ng/dL between 1999-2000 and 2015-2016"

My concern is not for the future of the human race, but for the effect on future PCa rates. Low T has been found to be a PCa risk factor.

-Patrick

[1] auajournals.org/doi/10.1097...

MP78-01 TRENDS IN SERUM TESTOSTERONE LEVELS AMONG ADOLESCENT AND YOUNG ADULT MEN IN THE UNITED STATES

Premal Patel , Richard Fantus , Soum Lokeshwar* , Joshua Halpern , Cecilia Chang , Atil Kargi , and Ranjith Ramasamy

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doi.org/10.1097/JU.00000000...

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Abstract

INTRODUCTION AND OBJECTIVE:

Testosterone deficiency has a prevalence of 10-40% among adult males and 20% among adolescent and young adult (AYA) men (males 15-39 as per the National Cancer Institute). With increasing prevalence of low testosterone in general population, we hypothesized that serum total testosterone (TT) levels will decline in AYA men. The objective of this study was to analyze serum TT levels in AYA males using data from the National Health and Nutrition Examination Surveys (NHANES) 1999-2016. We hypothesized that serum TT levels in AYA men have decreased over time.

METHODS:

NHANES is a nationally representative cross-sectional survey that examines the US population and over samples targeted populations, to obtain adequate samples for subgroup analysis and more reliable variable estimates. We found data cycles which had values for serum TT and analyzed changes in serum TT over time controlling for year of study, age, race, body mass index (BMI), comorbidity status, alcohol and smoking use, and level of physical activity. During the study periods, three different assays (Biotin-Streptavidin from 1999-2004, IS-Liquid Chromatography from 2011-2012 and High-Performance-Liquid-Chromatography Tandem Mass Spectrometry from 2013 onwards) were used; they have shown comparable testosterone values with only some additional accuracy in the latest modality.

RESULTS:

A total of 4,045 men had TT measured from 1999-2016. After controlling for confounders, TT was lower among men in the later (2011-2016) versus earlier (1999-2000) cycles (all p < 0.001). Mean TT decreased over time: 605.39 ng/dL, 567.44, 424.96, 431.76 and 451.22 for 1999-2000, 2003-2004, 2011-2012, 2013-2014 and 2015-2016, respectively (p < 0.0001). Elevated BMI was associated with reduced TT levels (p < 0.0001) with mean BMI increasing from 25.83, 27.21, 27.12, 27.81, 27.96 for 1999-2000, 2003-2004, 2011-2012, 2013-2014 and 2015-2016, respectively, p = 0.0006. Even in men with normal BMI (18.5-24.9), TT levels have declined from 664.79 ng/dL to 529.24 ng/dL between 1999-2000 and 2015-2016 (p < 0.05).

CONCLUSIONS:

This is the first study to report declining testosterone levels in adolescent and young adult men. Further studies are required to understand the etiology of low testosterone in AYA men.

[vforvendetta]

Thank you for sharing. This resonates with me because my father has PCa and I "feel" that I have Low T. He was diagnosed at 79, but I suspect that he had it well before then.

My Total Testosterone results:

2/2020(Age 46) 388 ng/dL

3/2017(Age 44) 280 ng/dL

4/2016(Age 43) 473 ng/dL

My urologist indicated that my T levels are fine for my age. My PSA in January of this year was .9 ng/mL and my DRE was normal. I will be tested yearly now because of my father's Gleason 9/aggressive PCa. I've had CT-Scans/Cystoscopy in 2017 for related urinary issues that came back "clean". I've had one bout of horrible Prostatitis when I was 41. To this day, whenever I urinate, I recall how bad the pain was 6 years ago. I described it as peeing lava mixed with broken glass :-).

I have some anxiety about the future, but don't really know what to do next. I have LUTS issues and am wondering if Low T is the root cause of them. If I do have Low T, then I need to decide whether to commit to lifelong TRT.

I read this yesterday, and it seems to indicate that TRT may help with LUTS => ncbi.nlm.nih.gov/pmc/articl...

The only medicine that I take is Cialis for ED/BPH. I'm not overweight, I don't smoke, I don't do drugs, and I've eaten mostly organic for several years now. I do drink a couple of craft IPAs a couple times a week (we all have to have a vice, right!?).

Do any members have any advice regarding TRT?

[Hidden in reply to vforvendetta]

I got two of my friends on TRT. They both say the same thing: they never want to stop. 200mg/wk of testosterone cypionate.

If you don't like needles perhaps androgel.

[LowT in reply to vforvendetta]

It is important to have a thorough workup BEFORE beginning any TRT.

In addition to the total testosterone should obtain free testosterone, LH, FSH, Estradiol, DHT at a minimum. Once you start taking hormones these can be effected for a long time so want to know the 'virgin' levels.

[pjoshea13 in reply to vforvendetta]

I have used testosterone [T] in different ways for 15 years [currently BAT].

I have noticed a bias in our culture - a resistance to changes that offend some. e.g. the idea that red wine might have some health benefits, that coffee might have anti-cancer properties, & the feeling that it is unseemly for men to fight the so-called andropause.

And so we have scare-mongering about the cardiovascular risk (from a discredited study).

You will notice that your red blood cell count will rise with TRT. Low T reduces RBC & can cause anemia. Some say that TRT will cause the opposite - erythrocytosis. In my case, RBCs moved to the middle of the normal range as my T rose to over 1,000 ng/dL. However, it is advisable to look at the effect on hematocrit levels when starting out [1].

In my view, given that estradiol [E2] often rises as T falls, the E2:T ratio is an important measure. It has been used in various studies, although rarely in PCa.

Most recent, from last month: "Relationship Between Penile Erection and the Ratio of Estradiol to Testosterone" [2]

From 2009 (Australia) [3]:

"Although androgens and estrogens both play significant roles in the prostate, it is their combined action--and specifically their balance--that is critically important in maintaining prostate health and tissue homeostasis in adulthood. In men, serum testosterone levels drop by about 35% between the ages of 21 and 85 while estradiol levels remain constant or increase. This changing androgen:estrogen (T:E) ratio has been implicated in the development of benign and malignant prostate disease."

E2 should be in the 20-30 pg/mL range. When T is restored, E2 tends to drop.

TRT may not change your weight, but the ratio of lean to fat mass will improve.

-Patrick

[1] en.wikipedia.org/wiki/Hemat...

[2] pubmed.ncbi.nlm.nih.gov/325...

[3] pubmed.ncbi.nlm.nih.gov/198...

[vforvendetta in reply to pjoshea13]

Thank you for the insightful and thoughtful reply. I'm meeting with my PCP at the end of the month and I'm going to request and extensive hormonal panel lab work up. My urologist has already stated to me on multiple occasions that this needs to be pursued by my PCP and not him. So I am going to finally listen to him.

It sounds like if I go on TRT I will need frequent lab work done to make sure things are tuned in and in order. I don't know if my PCP would be doing this or an endocrinologist or someone else... but I will learn along the way.

Thanks again.

[pjoshea13 in reply to vforvendetta]

You only need to test once really. To check that T is in the desired range. Doctors can be stingy in that regard. At least 650 ng/mL IMO. & to check hematocrit.

-Patrick

[noahware in reply to pjoshea13]

"When T is restored, E2 tends to drop."

This is confusing to me, since E2 results (mostly?) from the aromatization of T. It certainly makes sense the the RATIO of E2:T would drop as T is increased, but why does E2 decrease in absolute terms, too?

After all, when T is dropped via ADT, then E2 obviously falls as well. If you have any insight into this, I'm all ears!

[pjoshea13 in reply to noahware]

When I began to use androstenedione 15 years ago, I was worried about aromatase in PCa cells, so I used chrysin to inhibit that, i.e. the conversion of T to E2. I certainly think it good to monitor E2 & be prepared for an initial surge during TRT.

However, excess E2 is due to adipose tissue aromatization, & TRT leads to a reduction of fat mass (and a gain of muscle). Ultimately, a return to high-normal T should bring E2 down to the normal range. A man with a healthy muscle:fat ratio & a T of 1,000 ng.dL, say, has no need to worry that his high T is being converted to excess E2.

It used to be that doctors would not treat hypogonadism unless the man was in the hypogonadism range (<300 ng/dL was common not long ago & some used 250!) AND the man had actual symptoms (not midlife ennui.) The "therapy" was designed merely to get the guy over the cutoff - not what I would term 'restoration'. That isn't good enough to reset E2.

Yes, depending on how much adipose tissue there is & how low baseline T is, there could very well be a surge in E2. (I recommend Arimidex rather than chrysin.)

Thanks, -Patrick

[Hidden]

"Studies show that men’s testosterone levels have been declining for decades. The most prominent, a 2007 study in the Journal of Clinical Endocrinology and Metabolism, revealed a “substantial” drop in U.S. men’s testosterone levels since the 1980s, with average levels declining by about 1% per year."

Diet? Exercise? When I was in grade school we had PE 3 hours a week. My son has PE a total of 30 minutes a week. So we use a treadmill for 10 minutes a day and take Jiu-Jitsu lessons for 2-4 hours a week. People focus way too much on academics and not nearly enough on the things that make you truly successful.

Trend isn't good for many reasons.

[dmt1121]

I am 61 and I tell my wife that we are the DOW generation. Since the late 1800's plastics began to weave themselves into our lives. WWII saw the advent of useful items, such as nylon parachutes. It went on from limited applications until they were expanded for consumer uses in the 1960's and took over every possible industry. There are very few items in our homes, our offices or anywhere else that do not contain some plastic.

Synthetic plastics have been used for baby bottles, baby toys, children's toys, rotary telephones and a million other things from dinner plates to cups, and disposable eating utensils. We only recently discovered (officially) the instability of these plastics when heated and cooled, used for storing foods, water bottles to drink from while biking, hiking, etc. It's even in our clothing. The estrogens that leached out are now supposed to be gone with "BPA Free" plastic but tests have shown that estrogens are still an issue for these plastics too.

Then we have silicone rubber, also used in parts of bottles for sealing them against leaks, used in baby teething rings, cookware and so on that have been shown to leach siloxanes. A 2005 Danish Ministry report showed animal testing revealed lowered fertility and potential for being a carcinogen. The European Union considers siloxanes to be endocrine disruptors. foodpackagingforum.org/news... motherjones.com/environment... gq.com/story/sperm-count-zero

No study can truly prove any one product is a specific cause for sperm and testosterone drops but my bet is on plastics and siloxanes for a lot of it. We don't know what large corporations don't want us to know because it will reduce profits. Regardless of health impacts, I believe that manufacturers of these types of products will expand their consumer applications until there is no one left to count their profits.

The End.

[Cleodman in reply to dmt1121]

I agree that it is definitely something we are eating or drinking or wearing or otherwise using. I have no cancer in my family, have always eaten healthy and exercised regularly. Yet here I am at age 46 - 3 years into being diagnosed with metastatic prostate cancer and now failing all available treatments. As an ER doc I see so much cancer nowadays too. Especially in places that are agricultural belts. Tons of cancer in all ages. We are f-ing up the planet so it must be doing the same to our DNA.

[dmt1121 in reply to Cleodman]

I am very sorry to read your story. There are so many studies and theories but I think the fact that countries with a simpler lifestyle, little or no processed foods and values based on their community, family and friends have far lower cancer rates, says it all.

I agree with your hypothesis. We have outlived our welcome as a species on this planet and racked up a bill we cannot pay. Ironically, I believe many of the genetic defects we are trying to repair are ones we created.

I hope you have a longer life than you think to spend as much quality time with your love ones as possible. Laugh, hug and kiss everyone you can (air hugs count). I wish you a peaceful journey when the time comes.

Until then, let us know how you are doing and tell us the fun stuff!

[dmt1121]

pubmed.ncbi.nlm.nih.gov/268...

pubmed.ncbi.nlm.nih.gov/239...

ncbi.nlm.nih.gov/pmc/articl...

There are many more, but it is too depressing to consider the long term impacts on the health of our sons, daughters and grandchildren. Of course there is nothing conclusive but there sure is a lot of smoke for there to be no fire.

[ck722]

Our food supply. Did you know people in inner cities test positive for roundup? Potatoes and apples can be laced with high amount of synthetic bug and mold killers. Be careful.

[noahware]

As men age, there is a decrease in T and there is also a higher likelihood of co-morbidities like obesity, metabolic disease, etc. I would suggest the bottom line is this: more and more people are aging prematurely, for whatever reason(s), and that is reflected in an epidemic of chronic illness that impacts people's lives earlier and earlier even as medical progress extends their actual lifespans.

We are turning increasingly into a society of unhealthy people who live a long time! I suspect many factors are at play, including diet, pollution, lack of sun, destruction of circadian normalcy via artificial light and shift work, etc.

[Cleodman]

Not the greatest of studies in my opinion. Based on association and not really causation. My oncologist thinks the increase in PC is due to the high propensity of testosterone supplements. In the end PC is a hormone based cancer. Like breast and ovarian so I would be careful. I hear you though. Testosterone is wonderful and I really miss that “loving feeling”.

[pjoshea13 in reply to Cleodman]

Here is a 2017 study from MD Anderson [1]:

"Testosterone levels significantly decreased as PCa aggressiveness increased ...

"Compared with the normal testosterone group, the low testosterone group had 2.9-fold .., 5.6-fold ... and 72.4-fold ... increased risks of having intermediate-risk, high-risk and metastatic PCa, respectively.

"Furthermore, low levels of testosterone were significantly associated with a 10.7-fold ... increased risk of PCa-specific mortality.

"The results of the present study indicate that low levels of total serum testosterone at diagnosis are associated with aggressive PCa and predict poor PCa-specific survival."

Many find this counter-intuitive (even some doctors).

I believe that the numbers would have been worse had they excluded men with very low T - after all, those men are on ADT-lite & may be getting a little protection.

T replacement therapy [TRT] has now been much studied & the conclusions that I have read have been that TRT does not increase risk.

There is a nice study conducted by the VA which matched low-T men who requested TRT with those who did not. Those in the TRT group went on to experience less PCa.

Which leads me to think that young men with low T should demand TRT.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/284...

[noahware in reply to Cleodman]

"My oncologist thinks the increase in PC is due to the high propensity of testosterone supplements. "

I wonder, though, if he has any studies that really back that up, or if it is just his hunch. Could he just be perpetuating a myth? So much work has been done in the past decade that really points away from TRT as something that causes or accelerates PC, and I have seen very little solid research to counter that.

That PC is "hormone-based" does not mean an increase in T itself fuels the fire. Going all the way back to the 1940s, there have been observations of high-dose T being of actual benefit to some men with PC.

[Cleodman in reply to noahware]

Yeah maybe but I doubt it. Not saying the Mayo Clinic is the end all and be all of health care but in the medical world they only hire docs that are very well versed in research. Plus the drug insert for testosterone cypionate actually lists prostate cancer as a serious side effect (along with liver cancer) so if the drug companies are listing it...

I went off Lupron for 1 year and my cancer progressed with a vengeance when my testosterone recovered. Bipolar androgen therapy maybe a future modality being researched out of John Hopkins but we will have to see.

[noahware in reply to Cleodman]

If you have time, check out some of the "Grand Rounds in Urology" lectures given by Abe Morgenthaler on the topic. Pretty interesting. He notes that the original study leading to suppose T prompts cancer was actually based on a single patient! He has treated many men with PC with TRT with good results, as has Dr. Bob Liebowitz (who also has some very interesting lectures online).

[PCreader in reply to noahware]

where can I find Dr Bob’s lectures online? I’ve only found one so far.

[pjoshea13 in reply to Cleodman]

The insert in my T cypionate box lists PCa as a contraindication, but not an actual side effect, unless I missed it.

-Patrick

[j-o-h-n]

Plastic condoms.........

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 07/08/2020 1:57 PM DST

[pjoshea13 in reply to j-o-h-n]

I thought they were for vegans. They used to use sheep intestines back in the days when PCa was rare.

-Patrick

[j-o-h-n]

Makes sense with sheep..... trying to push the intestines back in......

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 07/08/2020 2:23 PM DST

[Hidden]

I don't think that many doctors/ urologists can be talked into prescribing TRT for someone like me with prostate cancer. I should have my T level checked. At age 70 and with zero ejaculate after TURP and then HIFU my obligation to go forth and procreate is hereby discharged. Is this fertility drop nature's attempt at population control or is it a function of our water supply being contaminated by hormone disturbing chemicals?

[DonUSNA73]

Would be interesting to compare trend among countries.