We're going to move away from libido and muscles for now.
Testosterone is so much more when you dig into the research.
Then, you look at how it drops roughly 1% from age 20 and you're wondering why everyone over 40-50 is not supporting this critical pathway.
Worse yet…the average T levels for a 20 year old have dropped in half over the last 20 years.
This is true for almost every age band and we'll discuss why below.
Our focus is going to be on every other aspect of health though:
- Mental health
- Immune function
- Cardiovascular health
- Metabolism (fat, sugar, and energy)
- Longevity
We'll also look at studies in 2013-2014 that just doomed the general reception for testosterone support and why they were so so flawed. Very similar to the 2001 WHI estrogen study for women.
These are the areas we'll cover:
- An intro to Testosterone
- What's killing testosterone these days
- Testosterone and mental health
- Testosterone and immune function (including cancer)
- Testosterone and cardiovascular health
- Testosterone and metabolism
- Testosterone and longevity
- The DHT question
- The testosterone safety profile
Let's get started!
An intro to Testosterone
T belongs to the class of steroidal hormones. Technically, it's an androgen which just means…pro-growth.
All our steroidal hormones come from a cascade that begins with….LDL…yes, the so-called bad cholesterol.
LDL - pregnenolone - DHEA - testosterone (with a few steps glossed over)
We have a big review on pregnenolone but both it and DHEA have interesting longevity effects (we'll cover later).
There are also fascinating studies where cholesterol levels normalize when pregnenolone is supplemented.
Watch this little trick:
HT lowered mean TC from 228.8 mg/dL to 183.7 mg/dL (19.7%) (p<0.05) in all patients. In 12 men of mean age 58, HT statistically significantly lowered TC from 227.9 mg/dL to 177.1 mg/dL (22.3%) (p<0.05). Apparently it did so mostly by lowering LDL and triglycerides (TRG) while HDL did not appreciably change.
https://pubmed.ncbi.nlm.nih.gov/21407165/
Essentially, by directly supplementing steriodal hormones (HT), total cholesterol dropped from 228 to 183. It was more pronounced in men.
Most interesting, LDL dropped (with triglycerides)...but not HDL.
Hmmm…it's almost like elevated cholesterol (LDL specifically) is just a work-around the body is doing to get ahold of more steroidal hormones.
So billions of dollars are spent on statins to squash cholesterol without addressing the core reason the body is elevating to begin with? We digress.
So…why is the body so anxious to get testosterone levels back up? It just for reproduction, right??
No!
T (as well as estradiol and progesterone) has receptors on EVERY cell of the body and brain.
Heart. Bone. Organ. Brain. Immune. Every cell.
Why?
Testosterone (like estrogen) is the repair, replenish, grow agent in the body.
It's fighting back against a range of assaults and related damage/deterioration!
- Stress
- Trauma
- Illness
- Injury
- Damage from oxidative stress
We're going to see specifics by area below.
T is as close to the fountain of youth that we have.
And it's quickly going away (maybe by Nature's design).
With a little help from us. Let's go there now.
What's killing testosterone these days
It's not looking good on the T front.
https://academic.oup.com/jcem/article/92/1/196/2598434?login=true
So from 501 to 391. About 20% drop. It's only gotten worse..
The 2016 study showed another 25% drop. It's declined further since:
Keep in mind that this applies to adolescent and young males as well.
They also took into account BMI, smoking, and other facets that directly affect testosterone.
So…what didn't they take into account?
We are surrounded by chemicals that suppress testosterone OR are estrogenic (which opposes testosterone).
The biggest culprit in our opinion??….the change of fat to seed oils with high Omega 6 content. We did a massive review on seed oils including steroidal hormone effects but the net net…
The intake of omega-3 polyunsaturated fatty acids was positively related to testicular volume while the intake of omega-6 polyunsaturated fatty acids and trans fatty acids was inversely related to testicular volume.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312216/
The key fat in omega 6 (and virtually all processed food with seed oils)...
Linoleic acid supplementation indicated estrogenic activity of Linoleic acid which was in consistency with serum estradiol level
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846030/
Our intake of seed oils as a percentage of total calories has exploded…roughly over the same time that testosterone has been dropping.
In fact…T levels in 1924 were about the same as in 1987 which is a good 20 years after soybean oil became the defacto source of cheap fat. (please read the review…T is just the tip of the iceberg).
Hmmmm. Interesting hockey stick there for "vegetable oils" with an explosion around 2000.
That's the easy culprit.
Then you have all the chemicals that are estrogenic and hormone-disrupting:
- Plastics such as phthalates, BPA, and more
- Chemicals in skin care products (sodium lauryl sulfates, etc)
- Pesticides, antibiotics, and hormones used in food production
We could go and on. Here's a good example of the skin care product:
https://www.tonyrobbins.com/health-vitality/are-mens-health-products-safe/
We're inundated in testosterone poison.
So…let's start to dive into why this matters.
First…to the brain.
Testosterone and mental health
We'll start with the sledgehammer. Serotonin.
Serotonin is the manager of ALL human behavior. Point.
Sure libido but also:
- Sleep
- Mood
- Learning
- Stress response
- Brain repair (BDNF)
- self esteem? Yes!
Serotonin is the target of antidepressants called SSRIs which boost it until they build tolerance (see SSRI review).
Turns out…we have a natural antidepressant that's dropping 1% each year from age 20.
Here's where it gets really interesting.
In the brain, testosterone is readily converted to estrogen due to a high level of aromatase in men.
Estrogen directly drives serotonin levels.
In fact (strange fact)...estrogen in the male brain is the real driver of libido!
Testosterone is more tied to aggression and drive.
Many of testosterone’s effects on the brain are paradoxically estrogenic in nature. This is because the rapid generation of estrogen from its yangian counterpart testosterone in the brain, an organ which is rich in aromatase
https://www.zrtlab.com/blog/archive/impact-hormones-serotonin-depression/
Let's look downstream at the most powerful player in all mental health and addiction…BDNF (our brain's fertilizer).
Ah ha…
Testosterone enhances functional recovery after stroke through promotion of antioxidant defenses, BDNF levels and neurogenesis in male rats
https://www.sciencedirect.com/science/article/abs/pii/S000689931400242X
Remember…we said T was the repair/replenish pathway after damage great (stroke) and small (stress).
You can't get to BDNF without serotonin which manages it. Check out the review on BDNF…it's really the superstar in the brain!
So…anti-oxidants, BDNF, and brain growth. Male!
This is all well and good but does it translate?
This systematic review and meta-analysis of 27 randomized placebo-controlled clinical trials involving a total of 1890 men found that testosterone treatment was associated with a significant reduction of depressive symptoms, particularly in participants who received higher-dosage regimens.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583468/
Hence, the term..."Mani-pause".
Okay…what about anxiety?
First, a quick note. Cortisol (our stress hormone) just kills testosterone.
Makes sense…danger out there….not a good time to reproduce.
A study looked at the effects of supplementation for men with low T versus placebo:
When compared with the baseline period, T replacement led to significant decreases in anger (P = 0.0045), irritability (P = 0.0009), sadness (P = 0.0033), tiredness (P = 0.0035), and nervousness (P = 0.0291), and significant improvement in energy level (P = 0.0020), friendliness (P = 0.0072), and sense of well-being (P = 0.024) in all subjects as a group.
https://academic.oup.com/jcem/article/81/10/3578/2649928
This was all about bringing T levels up to a normal range! Going further did not help.
T is a major mood manager - anger, irritability, sadness, tiredness, nervousness.
Really…friendliness!?!? Sense of well-being?
Just for reproduction folks.
Most people assume that T replacement will make us angry, irritable, and aggressive.
That's from the old "Anabol" days of steroid use to get levels way above normal. Superphysiological!
We know from above that many (maybe most) men are actually way under normal.
That's tired, irritable, depressed, nervous, etc.
We could go on and on. Let's turn to immune function.
Testosterone and immune function (including cancer)
Testosterone and estrogen are both huge drivers of immune function. Interestingly, women have progesterone to push back on estrogen.
Men don't have the same levels of progesterone (although we have some and receptors on every cell!) so T is more nuanced here.
Otherwise, you would see autoimmune, inflammatory diseases, etc.
First, we know that T directly drives immune function as shown by the most recent nasty experience:
Men with tT levels < 100 ng/dL had a more than eighteen-fold higher in-hospital mortality risk (OR 18.243 [95%CI 2.301 – 144.639], p = 0.006) compared to men with tT levels > 230 ng/dL
https://www.frontiersin.org/articles/10.3389/fendo.2021.694083/full
Vitamin D and estrogen are similar (both steroids!!).
18 fold increase in mortality. 230ng/dL isn't even baseline levels (which we'll discuss later).
The key takeaway with this complicated system…
In the case of low testosterone levels, such suppressive mechanism may be reduced, which might result in an imbalance between immunosuppressive and pro-inflammatory regulating mechanism in men
https://www.frontiersin.org/articles/10.3389/fendo.2021.694083/
Here's the strange part…T can both calm immune function and boost it in males. Selectively!
For example…
Higher endogenous testosterone was associated with down-regulated responses in all cytokines after PHA stimulation (but significantly in only 2/13 cytokines), controlling for age and body mass index. In contrast, testosterone was not significantly associated with down-regulation of cytokines after LPS stimulation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075254/
There, it's calming the response when hyperactivated!
The important takeaway…
Endogenous testosterone appears to be immunomodulatory rather than immunosuppressive.
It manages rather than just push/pull in one direction.
That may be why women get hit with 80% of autoimmune as progesterone (calms the immune) leaves the scene during 40's leaving estrogen (boosts the immune in one direction).
What about cancer which is governed by the immune system (cellular birth/death cycles)?
We'll get to the prostate question later (big news there lately) but what about cancer in general with low T?
There are clues...
Prevalence of hypogonadism in men with cancer has been reported between 40% and 90%, which is significantly higher than in the general population.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424192/
Hypo means low T.
And...
Hypogonadism is also associated with poor survival in cancer patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424192/
Okay…none of this makes sense since the general take out there is testosterone=cancer.
If T modulates the immune system and this system detects and removes faulty cells (with oxidative stress)...we need more data.
There's actually a clinical trial right now so we look forward to that detail.
Again…we're talking about bringing low T levels up to normal levels….not excessive amounts. And bio-identical!
After all, cancer is clearly age-dependent and T's dropping 1% each year. Big review on cancer here.
Let's turn to the heart.
If you take T, you'll get a heart attack in a fit of rage. Oh, please.
Testosterone and cardiovascular health
There is are a range of benefits from testosterone supplementation WHEN LOW for many facets tied to cardiovascular health.
- Improves insulin sensitivity
- Reduces body fat…especially belly fat and visceral (around organs) which is especially tied to cardiovascular risk
- Acts as a vasodilator
- Calms inflammation (which is critical to arteriosclerosis)
Still, there's is debate on testosterone and cardio risk.
Let's cut through it a bit.
First, hypogonadism….low testosterone.
Longitudinal studies showed that baseline testosterone level was significantly lower among patients with incident overall- and CV-related mortality, in comparison with controls.
https://eje.bioscientifica.com/view/journals/eje/165/5/687.xml
They also found that replacement therapy was tied to much better results on treadmill tests.
A study looked at men who had erectile dysfunction as a result of cardiovascular disease. Their primary goal was to see the effect on ED but they also tracked a range of cardiovascular markers:
Total weight loss was 23.6 ± 0.6 kg after 8 years. HbA1c had declined by an average of 2.0% (P<0.0001). Total cholesterol levels significantly declined following TTh after only 1 year (P<0.0001), and HDL increased from 1.6±0.5 at baseline to 2±0.5 mmol/L following 8 years of TTh (P<0.0001). SBP decreased from 164±14 at baseline to 133±9 mmHg, signifying a reduction of 33±1 mmHg (P<0.0001).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403087/
Okay…
- HbA1C - the current gold standard for heart risk (a measure of sugar damage to blood) went down. See review on glucose damage
- Cholesterol plummeted (go figure...remember the workaround theory)
- HDL went up
- Systolic blood pressure dropped 33 points!
Goodness. The HbA1C is the big one in our book.
Check out Dr. Attia's podcast on testosterone replacement. Excellent resource.
Inflammation and metabolic health are finally gaining ground as the core driver of cardiovascular risk.
Another study:
men in the lowest quartile of total testosterone levels had a 40% increased likelihood of 20-year mortality compared to those with higher levels, which could not be explained by a range of comorbidities and risk factors, including age (hazard ratio [HR] 1.40 [95% confidence interval {CI} 1.14-1.71]).
https://www.sciencedirect.com/science/article/pii/S2589790X21001335
So..the lower T, the higher the risk even when other comorbidities are taken into account.
Another big study on veterans:
In similar analyses, current use of intramuscular testosterone was not associated with risk for the composite cardiovascular outcome in men without or with prevalent cardiovascular disease (HR, 0.91; 95% CI, 0.80–1.04; HR, 0.98; 95% CI, 0.89–1.09, respectively).
https://www.ahajournals.org/doi/10.1161/JAHA.120.020562
Supraphysiological (much higher than normal range) is risky. Hence, the bodybuilder issues. Synthetics are an issue as well. We can blame them for much of the poor advice and warning around T for decades.
The newer research is showing reduced risk of normal ranged testosterone and cardiovascular.
Another study looked at testosterone supplementation versus control:
For the men under 55, the risk of heart attack and stroke was reduced by 25 percent; for men over 60, the risk was reduced by 15 percent.
https://www.eurekalert.org/news-releases/796591
We'll stop there. Clearly, T is critical to the working of our cardiovascular system.
Let's turn to metabolism (which feeds directly into cardio).
Testosterone and metabolism
As much aesthetics as health, metabolism deteriorates as T leaves the scene.
Connected?
Let's look at T and the following:
- Weight gain - especially belly fat
- Insulin resistance
- Cholesterol
- Sugar management
- Energy levels
Weight gain and testosterone - especially belly fat
Long-term testosterone therapy in men with testosterone deficiency produces significant and sustained weight loss, marked reduction in waist circumference and BMI and improvement in body composition. Further, testosterone therapy ameliorates components of the metabolic syndrome.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154787/
Goodness. A few notes.
First, "long-term". We don't want the body to push back against T in the form of tolerance. This happens with super high levels (bodybuilders)..hence breast, etc.
All facets improved:
- Weight
- BMI
- Waist circumference
Also, markers for diabetes (metabolic syndrome) improved as well!
Keep in mind that obesity or fat tissue itself suppresses testosterone function!
Fat tissue is not just a store of energy. It actively converts testosterone into estrogen:
Within fat tissue, enzymes such as aromatase and aldo-keto reductase 1C are responsible for metabolizing testosterone into estrogen and 5-dihydrotestosterone into inactive metabolites
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770848/
That's why men will gain breasts if they become obese.
So…it's a vicious cycle. Weight gain will suppress T (converting it to estrogen) which then causes more weight gain.
One of the biggest signals for cardiovascular risk in men is belly fat and fat around the organs. Visceral fat.
Testosterone administration to middle-aged men is associated with decreased visceral fat and glucose concentrations and increased insulin sensitivity. Testosterone infusion increases coronary blood flow.
https://academic.oup.com/cid/article/37/Supplement_2/S142/335512
That brings us to insulin and diabetes.
Insulin resistance
We'll jump right into the primary driver of diabetes and metabolic dysfunction.
For men…
There were significant interactions between testosterone and sex for all tested metabolic traits. Increasing testosterone was associated with less body fat, elevated insulin sensitivity, and reduced glycemia, independent of adiposity in men
https://www.frontiersin.org/articles/10.3389/fendo.2019.00090/full
The entire metabolic system! Fat. Insulin. Sugar. Goodness!
We say "men" because it had the opposite effect on women!
When doctors block testosterone function due to prostate cancer, what is the result?
A huge increase in diabetes!
ADT with GnRH analogs was associated with a 44% increased risk of incident diabetes (34% increased risk for orchidectomy) compared to controls
https://joe.bioscientifica.com/view/journals/joe/240/3/JOE-18-0573.xml
Let's turn to old tread.
Cholesterol
We've covered this a bit up top. Remember…LDL is the sole source of all our steroidal hormones and judging from above, T's pretty essential!
So…
Endogenous testosterone is associated with an antiatherogenic lipid profile with higher HDL-c and lower total cholesterol and triglycerides.
https://www.sciencedirect.com/science/article/pii/S0022227520345144
"Antiatherogenic" means anti-arteriosclerosis. Less build-up in arteries. Hmmm..
All facets improved.
What about the real enemy…sugar.
Sugar management
A German study looked at T in addition to medications for Type 2 diabetes versus control:
One-third (34.3%) of men treated with testosterone saw remission of their diabetes; almost half (46.6%) achieved normal glucose regulation with antidiabetic treatment and a vast majority (83.1%) reached their target level of HbA1c.
https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.14122
This was a long, 11 year study!
1/3rd saw remission. There's that HbA1c (marker for sugar excess damage - see our review on the problem with glucose).
Funny that HbA1c is also the gold standard for cardiovascular risk (see the glucose review!!!).
We'll get into why T keeps glucose under wraps below with the powerful AMPK pathway (key to longevity).
Remember way above how low T was tied to "tiredness" and T replacement resulted in more energy?
Energy levels
Metabolism is all about energy. Using it. Storing it. Transportation.
The enemy of everyone over age 40ish.
Fatigue.
T's a big player there.
In a multivariable analysis adjusted for age and hypertension, TRT >1 year was associated with a 14.8-point decrease in Fatigue Severity Score (p<0.001).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823386/
Okay…the total score for that test is 63 (9 questions; 1-7 score each).
A nearly 15 point drop is huge!
That was a 1 year study but keep in mind that it can take 18 months or more for T's effects to fully integrate (as per cardio studies).
What's driving this?
First, testosterone governs glucose (energy) uptake into muscles and bones. That's partially why it's not floating around in your bloodstream doing damage (insulin, etc).
But it goes deeper. Remember that T is the replenishment pathway.
Mitochondria…the literal energy plants of every cell in your body. Ancient bacteria we kidnapped…or "negotiated with" to power all multicellular life.
More on mitochondria function here.
T directly supports their function!
First…the broad strokes:
Our results showed that testosterone increased cell survival and reduced nuclear fragmentation and chromatin condensation. These effects were accompanied by preservation of mitochondrial function and an augmented expression of neuroglobin.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921852/
Goodness. We're talking about energy production AND the management of our epigenome (see editing your health code to learn why this is so important).
Love this study.
They blocked testosterone in mice and saw the following in the brain:
castration of male rats reduced the activity of mitochondrial complex I and downregulated the expression of ND1 and ND4 of 7 mitochondrial DNA- (mtDNA-) encoded subunits of complex I in the substantia nigra.
https://www.hindawi.com/journals/omcl/2017/1202459/
Literally…shutting down key parts of energy production in the brain.
They then supplemented D and the energy production came back online.
One note…when mitochondria aren't functioning correctly, you have a range of issues such as oxidative stress and inflammation. Not to mention…low energy system-wide!
Low mitochondria function is tied to aging and many aging-related diseases.
What a great segue.
Testosterone and longevity
We did a big review on steroidal hormones and longevity.
Let's zero in on testosterone.
Just logically, all the attributes we mentioned above (which are reversed by T supplementation) are tied to aging:
- Visceral belly fat gains
- Metabolism shifts
- Muscle atrophy
- Loss of libido
Let's zero in on key longevity pathways and see if T is involved.
We'll focus on the following first:
- AMPK - target of metformin and berberine
- SIRT - target of resveratrol and pterostilbene
First, AMPK.
An interesting study looked at T supplementation's effect on AMPK for men with low T.
The results:
Following testosterone replacement, the expression of AMPKα did not alter in the fasting state but increased markedly by 41% and 46% in adipose tissue and muscle, respectively
https://www.researchgate.net/publication/338082470
Here's the deal.
Men with low T show reduced AMPK activity in muscles and fat. After T, sugar is "brought" into this tissue (rather than being free-floating) and increasing AMPK.
This is thought to be the main driver behind improved glucose and insulin effects from T which we looked at above.
AMPK is a nutrient sensor so this makes sense. Learn all about AMPK and longevity.
Then there's SIRT.
A study looked at how T replacement protects against cognitive decline (ding ding ding…aging!)
Hello SIRT:
We observed that an NAD(+)-dependent deacetylase, SIRT1, played an important role in the protective effect of testosterone against oxidative stress-induced endothelial senescence. Testosterone increased eNOS activity and subsequently induced SIRT1 expression.
https://pubmed.ncbi.nlm.nih.gov/22238626/
Learn all about SIRT at our pterostilbene review or CBD and SIRT.
There's lots of conflicting information on T and longevity. First, we need to sequester just data on replacing T for LOW or hypofunction.
Going above the normal range is just as bad as being below.
Range bound.
Too low is bad:
Hypogonadal men have lower life expectancy than men with full androgenization and cardiovascular disease, obesity or diabetes is often associated with hypotestosteronemia. Low testosterone level is risk factor for these diseases
https://pubmed.ncbi.nlm.nih.gov/27734705/
We look forward to larger clinical trials but this synopsis sums it up:
The association of increasingly greater longevity at progressively higher testosterone levels suggests that the lack of testosterone causes or contributes to premature death. Furthermore, 9 studies have shown that testosterone therapy significantly increases longevity (or, if you prefer “lowers mortality”). In other words, older men who take testosterone may live longer.
https://www.worldhealth.net/news/can-men-live-longer-taking-testosterone-therapy/
The key takeaway is what happens when we supplement for men with low levels:
It was found that testosterone replacement therapy of men suffering from late-onset hypogonadism increased survival rate by 9-10% in 5 years, similar to that of eugonadal, non-LOH men with normal endogenous testosterone secretion.
https://pubmed.ncbi.nlm.nih.gov/25892327/
Let's break that down. Basically, supplementing T increased survival rates and brought them up to men with…normal T levels!
So the goal is…normal T levels. Go get tested. Good luck with that based on the worldwide drop over the past 40 years.
Check out the Steroidal Hormone and longevity review for lots of research!
Let's turn to the boogeyman.
The DHT question
The original big fear around T supplementation revolved around two issues:
- Prostate cancer
- Heart attack/Stroke
The studies that drove this fear (2013/2014) were deeply flawed…at best! Check out Dr. Attia's review of them.
Most of the prostate issue centers on DHT levels.
DHT is a much stronger version of testosterone. It spikes during puberty to "masculinize" the body and brain.
- Body hair
- Increase musculature
- Pronounced jaw
- Genitalia changes
Boys to men…although DHT would not make you a fan of the band.
Both testosterone and DHT operate on the androgen receptor but DHT is much stronger!
Dihydrotestosterone (DHT) is made from testosterone by an enzyme. DHT is five times more potent than testosterone. DHT is primarily used by the body in the prostate, skin, and hair follicles.
https://www.healthline.com/health/dht
As such, DHT drives growth but actually causes male pattern baldness (or may result from damage there…interesting new research).
Prostate cancer is a bigger issue as we get older.
Here's the strange piece. Prostate cancer risk increases as we get older when T is going down!! Almost entirely tied to old age when T is at its lowest.
Hmmmm.
We wouldn't be surprised if DHT is just a work-around by the body to make up for the loss of…Testosterone!
Average onset of prostate cancer is 66.
Look at the drop T levels:
https://eje.bioscientifica.com/view/journals/eje/173/6/809.xml
Huge drop right around 60-65. Hmmm.
What's interesting is that DHT doesn't drop much there. Remember…it's like 5 x T in terms of effect.
So the body is making up for loss T with increased DHT as a percentage of total androgen!
Very similar to what it does with cholesterol levels (the source of all steroidal hormones).
The anti-balding and prostate meds all block the conversion of T to DHT.
Ah ha!!
When circulating testosterone concentrations are low, intraprostatic DHT formation may become important in maintaining prostate growth, thus buffering the effects of decreasing testosterone levels, which has been suggested by Marks et al.36
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035750/#R34
T's important. The body will switch to DHT to make up for the loss (as in getting older).
So…the million dollar question…does T supplementation increase prostate risk as was blasted on headlines from the 2013 study?
A shift is afoot:
The longstanding dogma of the deleterious effects of TRT has recently been challenged, and it now appears that TRT may have an important therapeutic role in the treatment of hypogonadism in those men with either low-risk, active, or previously treated PCa.
https://www.liebertpub.com/doi/full/10.1089/andro.2020.0013
PCa is prostate cancer androgen gene, a risk factor.
Or..
Despite observed increases in prostate specific antigen (PSA), TRT does not seem to increase PCa recurrence rates when used cautiously, even in men with high-risk disease.9
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375443/
Or…
Not only can testosterone be safely utilized to alleviate AOH symptoms in prostate cancer survivors, it has been also touted as a treatment option for aggressive prostatic cancer.
https://www.nature.com/articles/s41443-020-00387-3
Wait a minute…using T to TREAT aggressive prostate cancer?
There's still a black box warning on T replacement around this issue. Most doctors are not keeping up with the newest data.
Pumpkin seed oil is a natural way to block the conversion of T to DHT by the way.
Let's turn to the safety and practical questions learned the hard way.
The testosterone safety profile and practical questions
So the big issues in those flawed 2013/2014 papers were around prostate cancer and cardiovascular risk (primarily heart attacks).
We've already looked at the prostate. What about cardiovascular beyond all the positives we see around metabolic, blood pressure, glucose, cholesterol, HBa1c, etc?
We have to look at new research which if finally getting to the bottom of this. Again, it comes down to level.
If levels are low, replacement is beneficial!
For the men under 55, the risk of heart attack and stroke was reduced by 25 percent; for men over 60, the risk was reduced by 15 percent.
https://www.eurekalert.org/news-releases/796591
And go figure:
The health of the men on testosterone therapy also improved by other measures. They lost weight, had more lean muscle mass, their cholesterol level and liver function improved, their diabetes was better controlled and their blood pressure dropped.
Maybe, they'll remove that ridiculous black box soon:
Over the past few years, the FDA has concluded that there is no evidence for significant CV risk for any given group of people treated with TRT.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164696/
Keep in mind that the benefits of testosterone replacement for cardiovascular function takes time…18 months in some studies.
3-5 year studies show profound effects so studies that look at 8 weeks or less did nothing to help the cause of understanding risk.
So…all this is around replacing T when low.
What's low?
Technically, it's under 300 ng/DL for total testosterone. Age drives the range quite a bit but like estrogen, do you really want 70 year range versus say 40?
"Normal" generally falls between 300-1000 although some men naturally go much higher.
Get tested. A good range is 500-800 as a baseline for replacement. Watch symptoms. Mood. Energy. Strength. Use those for signals for your body's particular "normal" range.
There are many facets driving testosterone function such as MAO which breaks down testosterone levels.
Vitamin D is also a key player in steroidal function and so many people are deficient. Aim for 50-70 ng/ml. It's a steroid itself!
Then, there's the type of T:
- Shots
- Under skin
- Topical
- Oral
- Sublingual
Our experience??
Topical is not great at getting into the blood. Lost 2 years doing that.
Shots require constant visits and the levels ping/pong between super high and super low (relatively speaking). That doesn't match the natural daily release of testosterone (early mornings).
Under skin implants dissolve more slowly but you have less control over levels.
Oral doesn't work well with T since it's hard on the liver.
We finally settled on sublingual daily T at 100mg. We get bioidentical T through a compounding formulary at about $75/month.
The levels have come up quickly (30 days) from about 200 to 500+.
The bioidentical is really important since synthetics never work as well and have their own risk profile (learned this the hard way from estradiol/progesterone reviews).
For now, this is the best approach we've seen.
Take T in the morning since it is stimulatory even though it improves sleep long term (the estrogen to serotonin to melatonin pathway in the brain).
That's a wrap! T came on the scene about 500M years ago. It's only in the last 20-30 that we have options to keep this repair/replenish pathway functioning as we get older!
Big review on Cold Exposure coming which may naturally boost T (and LH) significantly!
Related Research:
Steroidal hormones and longevity