Testosterone, Luteinizing Hormone and Mortality

[Ron Put]

5 hours ago, Matt said:

Okinawan's start off almost half the level of DHEA and Testosterone (if I remember correctly) than Americans but it declines much more slowly. Eventually, Okinawan's end up with higher testosterone levels at older ages....

I haven't seen a mention of this anywhere, so if you could post a source, it'd be appreciated.

The Korean eunuch stuff is a very small sample, and frankly, not worth much, except as clickbait for the popular press. As it was pointed out at the time, it didn't take into account lifestyle or diet, and it was contradicted by most other evidence. I also posted earlier a fairly convincing study which strongly supports the theory that largely testosterone-driven risky behavior, rather than physiological reasons, account for much of the difference in lifespan between men and women (and the rest is likely mostly accounted for by the double X chromosome in women). 

Here is a good review of the consequences of castration in the major centers where the practice was found:
Long-Term Consequences of Castration in Men: Lessons from the Skoptzy and the Eunuchs of the Chinese and Ottoman Courts
"Indeed, there are no valid data indicating that castration has any effect on life span of men."
https://academic.oup.com/jcem/article/84/12/4324/2864451

Here is a mention of a very small study of castrati, which also didn't find much of a correlation with life span (mostly here as a rather interesting read):
"The effect of castration on lifespan has been debated. In a small study I did on 25 documented castrato singers born between 1610 and 1762 the mean lifespan was 65·1 years (SD 12·1) and was similar to that of 25 intact male singers born between 1605 and 1764 who lived a mean of 64·9 years (13·1) (unpublished). The relative longevity for this period may be explained by the fact that both groups lived fairly cosseted lives.is contradicted by Italian castrati studies."
https://www.usrf.org/news/010308-jenkins_lancet.html

There is also evidence that castration used to treat prostate cancer increases the likelihood of cardiovascular ischemic events.

Anyway, this is simply an attempt to counter likely erroneous assumptions about normal levels of testosterone being detrimental to longevity (and 412 ng/dL, while on the low side for 35, is within the normal range).

Edited July 16, 2019 by Ron Put

[Ron Put]

I also ran across an interesting overview of another Blue Zone, Ikaria:

"In other studies, the metabolic syndrome (MetS) has been found to increase in prevalence among elderly individuals and seems associated with pathophysiological conditions that involve increased inflammation and oxidation process and mitochondrial and endothelium dysfunction. In previous studies testosterone levels have been found to be linked with cardiovascular health, as low testosterone levels seem to accompany aging-related diseases, like vascular dysfunction and atherosclerotic disease. In the IKARIA Study, the prevalence of MetS was associated with serum testosterone levels, only in men; at the same time, such relationship was not observed in women. Furthermore, serum testosterone levels were inversely associated with components of the MetS in both genders. When categories of lipids, hs-CRP, BMI, and insulin resistance levels were taken into account, testosterone lost its significance in predicting MetS, suggesting a mediating effect of these markers on the relationship between testosterone and the syndrome."
https://link.springer.com/referenceworkentry/10.1007/978-981-287-080-3_142-1

[mccoy]

16 hours ago, Matt said:

"Interestingly, out of the 81 eunuchs, three were centenarians, aged 100, 101, and 109 years. The current incidence of centenarians is one per 3,500 in Japan and per 4,400 in the United States. Thus, the incidence of centenarians among Korean eunuchs is at least 130 times higher than that of present-day developed countries."

This sentence captured my attention.

It doesn't seem to be a fair comparison, since it's a comparison by whole populations (Japan and USA) and a restricted sample. Even if we may consider the whole population of eunuchs, its numerosity would be hugely lower than that of the whole historical data of mortality (tens or hundreds of million data).

It's surely possible to apply a correction factor to the relatively small sample of eunuchs, but I wonder if the results would be statistically significant, moreover it seems that the life conditions were not equal, so the comparison would result to be biased a priori.

Edited July 17, 2019 by mccoy

[Saul]

Hi ALL!

Actually, I checked my bloodwork -- and my claims about my testosterone levels were incorrect.

The last time tested was late December, 2016:

Testosterone 795 ng/dL (standard range is 193-740)

Free testosterone: 50 pg/dL (standard range is 47-244)

Testosterone, % free:  1%

(Past results are roughly similar)

So, my testosterone is actually high -- above the top level in the standard range -- while my free testosterone is near the bottom of the standard range.  And only 1% of my testosterone is free.

Interesting.  So, despite my age (I'm 80), testosterone hasn't lowered.

Again, I think this is because my biological age is probably lower than my physical age.

(And, definitely, the sex drive hasn't disappeared.)

CRON, while initially lowering testosterone, is supposed to slow the normal decline of testosterone with aging.  Looking at my numbers, I don't show any decline in testosterone over time.

This is consistent with my other numbers -- lipid levels continue to be among the best in the CR Society.

  --  Saul 

[Ron Put]

4 hours ago, Saul said:

...

Testosterone 795 ng/dL (standard range is 193-740)

Free testosterone: 50 pg/dL (standard range is 47-244)

...

Wow! Better than the average Okinawan :)

These are levels which would be perfect for a 20 year old. For what it's worth, there is data which suggests that in healthy adults testosterone levels do not necessarily decline significantly until after the age of 75 or so. Just like blood pressure or cholesterol levels should not necessarily increase with age.

I keep seeing the claims that CR (without malnutrition) "initially lowers testosterone," but I have seen no real evidence that this is in fact the case. I am not saying it's an incorrect statement, but since it doesn't necessarily make sense to me, since testosterone levels correlate with lean mass, I'd love to see some real evidence.

Edited July 20, 2019 by Ron Put

[Saul]

Hi Ron!

I'm a CE agnostic -- but I do take cold showers.  I believe that cold showers are good for the skin.

I DO practice CRAN (I don't say CRON, because I don't think we know what balance of foods is optimal.)

  --  Saul

[Ron Put]

8 minutes ago, Saul said:

Hi Ron!

I'm a CE agnostic -- but I do take cold showers.  I believe that cold showers are good for the skin.

I DO practice CRAN (I don't say CRON, because I don't think we know what balance of foods is optimal.)

  --  Saul

Apologies, I typed "CE" by mistake above. I meant to type "CR" as in caloric restriction.

I'll correct it now.

[Dean Pomerleau]

1 hour ago, Ron Put said:

I keep seeing the claims that CE (without malnutrition) "initially lowers testosterone," but I have seen no real evidence that this is in fact the case. I am not saying it's an incorrect statement, but since it doesn't necessarily make sense to me, since testosterone levels correlate with lean mass, I'd love to see some real evidence.

I think you meant CR rather than CE. Here is the evidence that long-term CR lower testosterone and free testosterone in men (including myself) who had been practicing CR for many years from Luigi Fontana's 2010 study [1]:

 

An average testosterone of 12nmol/L among use CR practitioners equates to 345ng/dl.

My testosterone at the time Luigi tested us in St. Louis was 195 ng/dl. My most recent testosterone level was 352 ng/dl, right at the bottom of the reference range for a 54 year-old man. That is the highest reading I've had in the 19 years I've been on CR.

I've pointed you to [1] earlier in this thread, implying you don't consider it to be "real evidence." If this is the case, you have less of a grasp of what constitues evidence than I thought, which was already pretty low.

--Dean

------------

[1] Aging Cell. 2010 Apr;9(2):236-42. doi: 10.1111/j.1474-9726.2010.00553.x. Epub

2010 Jan 20.

Long-term effects of calorie restriction on serum sex-hormone concentrations in
men.

Cangemi R(1), Friedmann AJ, Holloszy JO, Fontana L.

Author information: 
(1)Center for Human Nutrition, Washington University School of Medicine, St.
Louis, MO, USA.

Calorie restriction (CR) slows aging and consistently reduces circulating sex
hormones in laboratory animals. However, nothing is known regarding the long-term
effects of CR with adequate nutrition on serum sex-hormone concentration in lean 
healthy humans. In this study, we measured body composition, and serum total
testosterone, total 17-beta-estradiol, sex hormone-binding globulin (SHBG), and
dehydroepiandrosterone sulfate (DHEA-S) concentrations in 24 men (mean age 51.5
+/- 13 years), who had been practicing CR with adequate nutrition for an average 
of 7.4 +/- 4.5 years, in 24 age- and body fat-matched endurance runners (EX), and
24 age-matched sedentary controls eating Western diets (WD). We found that both
the CR and EX volunteers had significantly lower body fat than the WD volunteers 
(total body fat, 8.7 +/- 4.2%; 10.5 +/- 4.4%; 23.2 +/- 6.1%, respectively; P =
0.0001). Serum total testosterone and the free androgen index were significantly 
lower, and SHBG was higher in the CR group than in the EX and WD groups (P < or =
0.001). Serum 17beta-estradiol and the estradiol:SHBG ratio were both
significantly lower in the CR and EX groups than in the WD group (P < or =
0.005). Serum DHEA-S concentrations were not different between the three groups. 
These findings demonstrate that, as in long-lived CR rodents, long-term severe CR
reduces serum total and free testosterone and increases SHBG concentrations in
humans, independently of adiposity. More studies are needed to understand the
role of this CR-mediated reduction in sex hormones in modulating the pathogenesis
of age-associated chronic diseases such as cancer and the aging process itself.

DOI: 10.1111/j.1474-9726.2010.00553.x 
PMCID: PMC3569090
PMID: 20096034  [Indexed for MEDLINE]
 

[Saul]

Hi Dean!

Are you referring to total testosterone or free testosterone?  In my case, free testosterone is 1% of my total testosterone; free testosterone is near the bottom of the normal range; total testosterone is above normal.

  --  Saul

[Saul]

Hi Dean!

Hmmmm....

My testosterone is in ng/dL.  your figure in ml/dL.  It's not clear how to convert.  It clearly depends on the molecular weight of testosterone -- which is 288.4 g/mole.  You'll probably figure it out faster than I will.

  --  Saul

Edited July 20, 2019 by Saul
Give more data

[Dean Pomerleau]

Saul,

Those reading are my total testosterone, and yes they are in ng/dL (I mistyped in my previous post). The reference range is 348-1150 ng/dL, so my latest, highest reading of 352 ng/dL is right at the lower bound of the reference range.

My free testosterone has ranged between 1.0 and 3.4 pg/mL over my CR bloodwork history. The reference range is 6.8 - 21.5 pg/mL.

--Dean

[Saul]

1 hour ago, Ron Put said:

Testosterone 795 ng/dL (standard range is 193-740)

Free testosterone: 50 pg/dL (standard range is 47-244)

 

1 dL = 10 mL.  So 50 pg/dL = 5 pg/mL.  So, if your reference range is correct, my free T is higher than yours, but also lower than the reference range.

You have a reference range for total T is 348 - 1150 ng/dL.  So my total T is in the middle of the range

Here's a table of my numbers:

Standard Range	3/17/13	12/15/13	7/23/14	4/2/15	12/23/16
Testosterone 193 - 740 ng/dL	616	922	786	659	795
Testosterone,Free 47 - 244 pg/mL	44	75	68	57	50
Testosterone,% Free %	1	1	1	1	1

 

[Ron Put]

1 hour ago, Dean Pomerleau said:

... An average testosterone of 12nmol/L among use CR practitioners equates to 345ng/dl.

....

I've pointed you to [1] earlier in this thread, implying you don't consider it to be "real evidence." If this is the case, you have less of a grasp of what constitues evidence than I thought, which was already pretty low.

--Dean

...

 

Really, Dean...?!!

No, I don't think that the "study" you are citing is good evidence. It's a very small, self-selected group, with no baseline. And it contradicts other studies, which find elevated testosterone levels in populations consuming fewer calories than baseline (with no malnutrition), as well as the well-established correlation between lean mass and testosterone levels.

I don't particularly care about your opinion, or your personal testosterone level. But please refrain from throwing insults just because you disagree with my arguments.

Edited July 20, 2019 by Ron Put

[Saul]

Clearly your (Dean's) testosterone numbers are better than mine.

  --  Saul

[Dean Pomerleau]

Saul,

This whole thread is about whether or not lower testosterone is "better" in the context of CR. It is an open question, but lower is in agreement with rodent CR data. Your testosterone reference range is likely lower than mine because I'm 26 years younger than you are.

--Dean

[Dean Pomerleau]

Reference ranges for testosterone are apparently all over the map, varying from one lab to another:

https://www.aacc.org/publications/cln/cln-stat/2016/june/16/testosterone-reference-ranges-vary-widely-in-us-laboratories

Except for my WUSTL test, all of my testosterone and free testosterone blood tests have been done at LabCorp, and I verified on the original paperwork that  the reference ranges I listed above were what LabCorp was reporting at the time (i.e. 348-1197 ng/dL for serum testosterone, and 6.8-21.5 pg/mL for free testosterone).

As of today, LabCorp says the reference range for men are:

Total Testosterone: 264-916 ng/dL (all ages)

Free Testosterone:  (pg/mL)
                                    6.8-21.5 (40-49 yo)
                                    7.2-24.0 (50-59 yo)
                                    6.6-18.1 (>59 yo)

--Dean

 

[Ron Put]

32 minutes ago, Saul said:

So, if your reference range is correct, my free T is higher than yours, but also lower than the reference range.

...

Saul, I believe that you quoted me erroneously and meant to refer to Dean's numbers -- I have not posted my testosterone levels in this thread.

For what it's worth, your 1% free T is still great for an 80 year old. The normal free T is usually about 2% of total testosterone (the rest is bound to SHBG and albumin). As one ages, there is usually a process of increasing bondage, which can result in insufficient free T for muscle development and other functions. But I'd guess since your total T is close to 800ng/dL, even 1% is sufficient to do its job.

[Saul]

16 hours ago, Dean Pomerleau said:

Reference ranges for testosterone are apparently all over the map, varying from one lab to another:

https://www.aacc.org/publications/cln/cln-stat/2016/june/16/testosterone-reference-ranges-vary-widely-in-us-laboratories

Except for my WUSTL test, all of my testosterone and free testosterone blood tests have been done at LabCorp, and I verified on the original paperwork that  the reference ranges I listed above were what LabCorp was reporting at the time (i.e. 348-1197 ng/dL for serum testosterone, and 6.8-21.5 pg/mL for free testosterone).

As of today, LabCorp says the reference range for men are:

Total Testosterone: 264-916 ng/dL (all ages)

Free Testosterone:  (pg/mL)
                                    6.8-21.5 (40-49 yo)
                                    7.2-24.0 (50-59 yo)
                                    6.6-18.1 (>59 yo)

--Dean

 

 

16 hours ago, Dean Pomerleau said:

Reference ranges for testosterone are apparently all over the map, varying from one lab to another:

https://www.aacc.org/publications/cln/cln-stat/2016/june/16/testosterone-reference-ranges-vary-widely-in-us-laboratories

Hi Dean!

Interesting.  The numbers that I quoted was done at UMRC (University of Rochester Medical Center).  I have no idea if it was done in house or sent out.

I do know that my Endocrinologist, who has full access to all my test results, was impressed by my numbers -- saying that he was impressed with how large the total testosterone was -- and indicating that he thought it was a consequence of my CR diet.  The endocrinologist is aware of the bloodwork numbers for a large number of people here at UR; so my total testosterone must be a large number. 

[Matt]

This thread reminds me that it's probably time for some more blood tests. I haven't done any in years...

Only measured Testosterone twice

516 ng/dl (2013)

412 ng/dl (2016)

Ref: 8.8 - 36.7 nmol/l (260-1080ng/dl)

https://docs.google.com/spreadsheets/d/1V6gvGoCnZGqcr-sR5TuFY4TKLr4mj_X6f7TlXJaLwk4

I've also taken Finasteride since the end of 2016.

Edited July 21, 2019 by Matt

[AlPater]

When I was much underweight, my testosterone went down to 5.8 in March/2002 (reference range 31-163 nm) and my last one with normal range in July/2018 weight was 24.81 (5.8-28 nm).

It is funny when Ron talks about how much testosterone is bound in terms of "bondage".

Edited July 21, 2019 by AlPater

[Ron Put]

5 hours ago, AlPater said:

It is funny when Ron talks about how much testosterone is bound in terms of "bondage".

LOL, glad to meet an AI with a sense of humor :D

Free (enough) testosterone from bondage, because without freedom for T, we shall all be bound:
 

• A 2005 study of 565 World War II veterans found that higher testosterone levels in midlife were linked to better preservation of brain tissue in some, but not all, regions of the brain in late life.

• A 2004 study of 400 men age 40 to 80 found that higher testosterone levels were associated with better cognitive performance in older men. No link was observed in younger individuals.

• A 2004 report from the Baltimore Longitudinal Study of Aging evaluated 574 men over a 19-year period. Low free testosterone levels predicted an increased risk of developing Alzheimer's disease, even after other dementia risk factors were taken into account.

• A 2002 study of 310 men with an average age of 73 found that higher levels of bioavailable testosterone were associated with better scores on three tests of cognitive function.

• A 2002 study of 407 men between the ages of 51 and 91 found that men with higher free testosterone levels achieved higher scores on four cognitive function tests, including visual and verbal memory.

• A 1999 study of 547 men between the ages of 59 and 89 found that high testosterone levels in older men were associated with better performance on several cognitive function tests.
  
  https://www.health.harvard.edu/press_releases/testosterone-and-memory

Based on the majority of the evidence I see, CR without malnutrition appears to boost relative testosterone levels. Malnutrition does appear to cause a drop in testosterone levels, which in turn can cause a host of issues:

https://www.sciencedirect.com/topics/medicine-and-dentistry/androgen-deficiency

 

[Ron Put]

Just came across an interesting article suggesting that high SGBH (which implies lower free T) is beneficial. It would seem that high total T combined with high SGBH may be the golden combination --  Saul's high T and 1% free T may be explained by high SGBH. There are appears to be some genetic component:

Recent studies have identified that there may be a link between SHBG levels and insulin resistance in type 2 diabetes. It has been suggested that SHBG may have a causal role in the risk of type 2 diabetes since Mendelian randomization studies have reported that carrying specific SHBG single-nucleotide polymorphisms affects the risk of type 2 diabetes ⁷⁾. Carriers of rs6259 polymorphism were shown to have higher SHBG levels and a lower risk of type 2 diabetes, and rs6257 single-nucleotide polymorphism carriers were reported to have lower SHBG levels and higher risk of type 2 diabetes ^😎. In another larger study including 86138 adults, presence of the rs1799941 SNP was associated with increased SHBG concentrations and reduced risk of type 2 diabetes after correction for age, sex, and BMI ⁹⁾. In a recent study, Wang et al ¹⁰⁾ showed that circulating SHBG levels were predictive for future insulin resistance in healthy young Finnish adults, whereas Mendelian randomization suggested minor, if any, causal effects.
https://healthjade.net/shbg/

[Saul]

Hi Ron!

I looked up SHBG in Wikopedia -- the beginning of the article:

Testosterone and estradiol circulate in the bloodstream, loosely bound mostly to serum albumin (~54%), and to a lesser extent bound tightly to SHBG (~44%). Only a very small fraction of about 1 to 2% is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. 

So having only 1% of my total T available as free T seems to be the default.

??

  --  Saul

 

[Ron Put]

From what I read, free T is normally about 2%-3% in the average adult male (e.g., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2544367/ ), probably closer to 2%.

If total T is toward the bottom of the scale, 1% is on the low side and it can affect one's functions, including muscle-building ability. Of course, the crucial point is, 1% of what? If of 300, then it's certainly too low. But if 1% of 900, then it's good. Which is what the first article I posted seems to imply, and why it reminded me of your (Saul's) case.

Do you know your SHBG values? My guess is they would be on the higher side.

Edited September 14, 2019 by Ron Put

[Saul]

Last test for testosterone was in 2016:

TESTOSTERONE TOTAL FREE - Details

About This Test

 

Component	Your Value	Standard Range
Testosterone	795 ng/dL	193 - 740 ng/dL
Tanner Stages Reference Ranges (ng/dL) Female Male Tanner Stage 1 < 3-6 < 3 Tanner Stage 2 < 3-10 < 3-432 Tanner Stage 3 < 3-24 65-778 Tanner Stage 4 < 3-27 180-763 Tanner Stage 5 5-38 188-882
Testosterone,Free	50 pg/mL	47 - 244 pg/mL
Testosterone,% Free	1 %	%