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Testosterone, Luteinizing Hormone and Mortality


Dean Pomerleau

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Notice:  Total Testosterone is actually high -- but free testosterone is near the bottom of the "normal" range.

My recollection from Luigi's study:  Free T is usually low when on CR.  I don't recall any details about total T.

Dean probably would have that info.

My previous test results on T are similar to the above.

  --  Saul

 

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Taken in 2017:

 

Sex Hormone Binding Glob 150 nmol/L 10 - 80 nmol/L
So -- like T (but not free T), it's high.  In fact SHBG is very high (compared to the normal range).  I don't remember if this is typical for CRON.  (Again Dean probably has this info readily available.)
  --  Saul
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Saul,

Below is the data on total T and SHBG in absolute terms and as a function of BMI from the WUSTL human CR study [1] in which both you and I participated.

--Dean

Screenshot_20190914-200628_Chrome.jpg

Screenshot_20190914-200117_Chrome.jpg

Screenshot_20190914-200005_Chrome.jpg

 

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[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]
 

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Low total testosterone and high SHBG are certainly not likely to be optimum for good health, based on what I read, as it would normally mean not enough free T.

Ultimately, too little available testosterone correlates with higher mortality, in fact more so than having T which is too high (over 1500). All I was saying was that Saul's high T was balanced out by the high SHBG, while still providing enough T for the functions required for optimum health.

The genetic predisposition to high T in the article I cited was more interesting to me.

Edited by Ron Put
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  • 4 months later...

Assuming one wanted to increase T (the value of which is still debatable) I was looking for dietary interventions that might help (the only thing mentioned in this thread was vitamin K / natto).

I found this review paper

Beyond tribulus (Tribulus terrestris L.): The effects of phytotherapics on testosterone, sperm and prostate parameters Heitor O. Santosa,⁎ , Scott Howellb , Filipe J. Teixeirac a School of Medicine, Federal University of Uberlandia (UFU), Uberlandia, Minas Gerais, Brazil

 

Journal of Ethnopharmacology

Volume 235, 10 May 2019, Pages 392-405

Conclusion: Scientific evidence supports the use of mucuna (5g/day) and ashwagandha (5g/day) as phytotherapics for improving serum T concentrations and semen parameters.  Data suggests an increase in total T with the use of 5000 mg/d of powdered mucuna seed and ashwagandha root (151 and 143 ng/dL, respectively) over a 12- week period in patients with oligozoospermia. 

That conclusion seems to be based on these two studies:

Effect of Mucuna pruriens on semen profile and biochemical parameters in seminal plasma of infertile men

and

Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males

It would be interesting if someone here did before and after bloodwork on T levels using either or both of the protocols described in these studies.  Mucuna is a bean, ashwagandha is a root, both are pretty inexpensive for a 90 day supply (1lb = 454g / 5g per day = 90 days, which would match the duration used in the studies above).

 

 

Edited by Gordo
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  • 3 weeks later...

This is the most recently active of many CRSociety threads on testosterone (T). Some others: 12, 3. There are several related but somewhat different topics:

(A) Is the low-T that results from CR bad? Does boosting it reduce the benefits of CR?
(B) In those not doing CR but also not obese / suffering from metabolic syndrome, is age-related decline of T bad and is boosting it back to earlier levels net long-term healthy?
(C) In those doing CR is the (perhaps slower) age-related T decline bad & boosting it back to youthful CR levels (but not back to non-CR levels) net long-term healthy?
 
I'm most interesting in the question of whether boosting T to stop age-related decline has clearcut health risks for those without metabolic syndrome / obesity, whether case B or C above, i.e. deep in CR or borderline (eg, WFPB or generally healthy obesity-avoiding lifestyle).
 
I'm curious what everyone (especially Michael) thinks are the best arguments not to intervene to raise T to prior youthful levels (for whatever level of CR / leanness one maintains) as one ages, assuming one has records of prior levels going back some years? Is there really much trustworthy data to make any informed decision about this?
 
Are there any studies that boost T in aging CR'ed mammals to maintain non-declining levels with age?
 
Michael mentioned that castration lengthens the life of dogs. I haven't tried to dig up the studies. Which ones do you find most compelling? Do the castrated dogs have lower overall leanness? Any data on whether castrated, CR'ed dogs live longer than non-castrated but CR'ed dogs?
 
 
More details.....
 
It's clear there is controversy about whether low T is bad & boosting it good, both in the wider medical community for the general population and here on these forums.
 
General population:
 
Pro-T example: StemTalk podcast just had interviewed Abe Morgantaler, an human T expert with long Harvard credentials. The episode discusses history of the the subject from the medical community perspective, eg risk of prostate cancer, also CVD. I don't have a broad enough view to know how one-sided the presented history is, but clearly he is an advocate of T therapy. Positive evidence is discussed as well as quality of life patient anecdotes. A lot of time is spent discussing flaws in studies that caused negativity for T therapy (and some of this is generally interesting from on the issue of science errors & publishing). This interview just came across my podcast feed and isn't meant to be the best single summary of the pro-T case.
 
Anti-T example: Michael, in one of the other threads, pointed out this article that summarizes a lot of evidence against T therapy. The author of this article is accused in the comments of the article of being biased against T therapy (opposite of the podcast interviewee above). [Note that Michael originally linked to the printable version of the article, possibly just to get to the unpaginated 1-HTML page version, but that doesn't include the comments.] The comments also point out some purported flaws in some of the studies discussed (eg differences in plaque scores in treatment vs. control groups before therapy was initiated in one study). The podcast interview above also discusses flaws in several studies---I didn't go back and try to match up the studies but I suspect many are covered in both places. I didn't try to dive into each study and its criticisms to try to decide each case myself. Michael's summary was:
"a series of reasonably-sized, well-controlled trials of T replacement in otherwise-healthy older males has once again shown that testosterone replacement in aging males has no durable benefits, and accelerates existing atherosclerosis"
 
It should be noted that "otherwise health" here means healthy by the definition of the normal medical healthcare system that defines lack of full blown clinical disease as "healthy", but many (most?) of the studies used people who had high BMIs, ate typical diets, and thus mostly had underlying molecular accelerated aging that meant that they were already well on the road to chronic diseases and metabolic syndrome given their ages. We could dive into the studies of such people as they are and discuss the details to figure out which studies are most trustworthy and try to guess at which conclusions carry over somewhat to leaner humans---that's one direction this thread could go if anyone cares to.
 
 
For CR or low-BMI healthy diet/lifestyle:
 
 
The T threads here discuss many things, including whether CR lowers T, whether CR or near-CR causes the age-related rate of decline of T to be slower.
 
[Note: Below I will just say (near)CR as a shorthand catch-all abbreviation for all of CR and other generally healthy obesity-avoiding diets, such as WFPB, Okinawans, etc. CR vs. these others is obviously different, but for the purpose of this discussion the difference between all of these and typical western diets in the important distinction.]
 
The thing most everyone agrees on is that typical bad diets lead to obesity / metabolic syndrome (metS) and simultaneous reduction of T (in humans, and seemingly in other animals too I think). Consequently, there is naturally much epidemiological data showing correlations between low T and bad health outcomes, but this correlational data is (near-)worthless for arguing that low T in the context of (near)CR is bad. It seems to me, even randomized trials in which T is artificially lowered or raised in high-BMI subjects eating bad typical diets should be viewed with caution as to relevance for those doing (near)CR.
 
Unsurprisingly, there is little to no data from well-done studies of (near)CR humans randomized to interventions that raise or lower T and then followed for long-term health. There just aren't enough (near)CR'ed humans in long-term studies let alone ones with this particular kind of randomized intervention. Are there good studies in rodents or other mammals that are CR'ed and then randomized to T-lowering or T-boosting interventions?
 
My read of the existing threads on these forums and everything else I've found so far is that there is insufficient evidence to conclude that age-related low T in (near)CR is clearly bad, nor that it definitely is safe. No one really tried to discuss whether intervening to increase T (via supplements or direct use of T therapy) to correct age-related T decline would be bad for (near)CR humans. I don't see much evidence at this point to conclude it would be bad (nor that it would be safe).
 
The best argument presented against boosting T so far seems to be the increased CVD risk, but even to the extent true in high-BMI/bad-diet individuals, how relevant is that for those doing (near)CR, whose CVD risk should be very low? What's the best argument that someone doing (near)CR would likely or possibly be doing harm to their long-term health by trying to slow or fully correct for age-related T decline by intervening to boost T?
 
If there is insufficient evidence to conclude that low T is bad, and insufficient to conclude that boosting T back to youthful levels is bad, then it becomes at matter of intuition & guesswork played off against personal preference for how someone wants to live their life (and strength of that personal preference vs. width of the error bars on the best estimate one can come up with from the data available). Michael in one of the other threads pointed to a non-scientific episode of This American Life discussing some of the huge life changes that low vs. high T can have on a person's life (quality of life, tastes and desires, even personality). These are things reasonable people may have strong personal preferences about.
 
I'm not having any particular low-T problems, but I see my free T levels starting to decline over time (in the context of stable diet & BMI) and personally don't have a desire to roll the dice on a changing personality---I like the one I have now thank you very much, nor roll the dice on some of the problems the patients in the Abe Morgantaler podcast episode talked about. Nor do I welcome energy level decline and I wonder whether caffeine use and variability may mask my ability to perceive a slow energy decline over time.
 
Karl
 
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This paper seems to suggest that males are unaffected by castration, while females do better.  The effect of dog sizes also seems to be interesting for me.  The chihuahua lifespan figure in the paper seems to be at odds with other figures.

DogBreedsLongevity.pdf

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On 2/29/2020 at 9:56 AM, AlPater said:

This paper seems to suggest that males are unaffected by castration, while females do better.  The effect of dog sizes also seems to be interesting for me.  The chihuahua lifespan figure in the paper seems to be at odds with other figures.

DogBreedsLongevity.pdf

The forums give me an error message on this way of attaching a whole file to a message, if I'm not logged in. Works fine if logged in.

For those not logged in, the paper is: https://www.sciencedirect.com/science/article/pii/S1090023313004486?via%3Dihub or https://doi.org/10.1016/j.tvjl.2013.09.020

So this study showed no advantage for neutered male dogs. This quote: "In the UK, neutering was associated with increased longevity for females but not males (Michell, 1999), while neutered males outlived entire males among US military dogs (Moore et al., 2001)." shows another UK study showed the same and a US study showed an advantage (in military dogs specifically). I wonder if that's explainable based on more risky behavior, as supposed as a confounder for the human eunuchs.

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  • 1 month later...
On 3/3/2020 at 9:21 PM, kpfleger said:

... I wonder if that's explainable based on more risky behavior, as supposed as a confounder for the human eunuchs.

It's quite likely that this is a valid explanation.

It appears that being within normal T levels is good, and maybe being in the upper range (without supplementation) as one gets older is beneficial to longevity. 

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So far no replies to my Feb 28 message with any compelling evidence-based reasons for those on (near)CR diets not to try to combat age-related testosterone loss by boosting it back to former personal levels. (Perhaps the timing is such that everyone quickly got distracted by the pandemic and this topic suddenly seemed less important.)

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  • 2 months later...

Out of curiousity, I checked my last T 5 testosterone tests:

TESTOSTERONE TOTAL FREE - Past Results

Printer friendly page--New window will open
Select a date range or total number of readings to graph.Starting dateEnding dateTotal number of readings to graph.From Calendar - Use to Select a Date to Calendar - Use to Select a Date - or - latest values
 
 
 
 
(hide)
Dates as columns
Dates as rows
 
Name
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  
Name
Standard Range
           
Testosterone
193 - 740 ng/dL
           
Testosterone,Free
47 - 244 pg/mL
           
Testosterone,% Free
%
           
 
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Saul, as I've noted before, your numbers are actually great (and I don't believe that you are supplementing). If I recall, kind of like the testosterone numbers found among the Okinawans, back when they were effectively practicing CR and were beating all longevity records as a group.

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