Use Testosterone for Heart Health

You Can’t Ignore the Mountain of Evidence

Research shows that testosterone replacement therapy (TRT) can do great things for the heart. Too bad it’s been largely ignored… until now.


A couple of years ago, the FDA issued a warning statement about the possible cardiovascular disease (CVD) factors associated with testosterone replacement therapy (TRT).

Their warning was largely based on two studies, the first of which indicated that younger men – with pre-existing heart problems – were more likely to have non-fatal heart attacks if they used TRT. The second study concluded that TRT substantially increased the risk of heart attack in younger and older men.

Never mind that the two studies were heavily criticized by other scientists for not bothering to take into consideration before and after testosterone levels in the subjects, neglecting to measure or account for estrogen levels (which plays a prominent role in the health of the heart), and for using a questionable control group.

The reality is that these studies were huge outliers. The only reason you might have been aware of them in the first place is because studies that warn of dire health consequences are like catnip to news organizations.

After all, if you see a headline that says something scary, like “This Over-the-Counter Drug Can Make Testicles Explode,” you’re surely going to click on it. The same goes with all things scary to the heart.

As a result, the public has been given a false impression of the safety of TRT. Fortunately, a group of Portuguese scientists looked at the evidence – all the evidence – and found that testosterone therapy, or having normal to high levels of the hormone in the first place, does the heart all kinds of good.

Is There an Association Between T and CVD Risk Factors?

It’s undeniable that there’s an association between men with Type 2 diabetes, obesity, hardening of the arteries, and metabolic syndrome (a condition characterized by elevated fasting glucose, obesity, high blood pressure, and undesirable cholesterol profile) and low levels of testosterone.

It’s also undeniable that the incidence of heart attack increases in aging men, which is when testosterone levels decline. That in itself makes you question the notion that high testosterone or TRT plays the role of villain in CVD.

Of course, the association between the CVD risk factors might be a chicken and the egg thing. Maybe those risk factors led to low testosterone in the first place, rather than the other way around, and maybe the low testosterone levels seen in the elderly play a smaller role in heart disease than a number of other factors (cumulative wear and tear, years of eating a bad diet, etc.).

What we need to do is look at these CVD risk factors independently.

Testosterone, Type 2 Diabetes, and Metabolic Syndrome

Metabolic syndrome is a serious thing. Patients with the syndrome have twice the risk of developing CVD in the next 5 to 10 years than those who don’t, and a five-fold increased risk of developing Type 2 diabetes in the same time frame.

TRT, however, has been shown to be an effective treatment to improve metabolic control in several studies. Likewise, TRT has also been shown to restore “glucometabolic” control in patients with Type 2 diabetes and reduce the risk of mortality from this common disease.

The conclusion drawn by the Portuguese scientists, after looking at all the research, was that “low T levels are associated with an increased risk of metabolic syndrome and Type 2 diabetes… and the beneficial effects of testosterone replacement are not only associated with fasting glucose, glycated hemoglobin and cholesterol levels, but also with obesity…”

Testosterone and Obesity

Obesity is an undisputed risk factor for the development of CVD, but the relationship between testosterone and obesity is a bit tricky, as each of these two factors potentiates the adverse effects of the other.

It’s the nature of fatty tissue to convert T to estradiol through the actions of the aromatase enzyme that’s found in high(er) concentrations in fatty tissue. An increase in the amount or size of fatty tissue increases aromatase levels and aromatase expression, and in turn this elevated estrogen level tells the pituitary to stop signaling the testicles to manufacture more T.

In turn, the increase in obesity leads to decreased levels of T, but these decreased levels of T, in turn, lead to increased levels of fatness. Oy vey it’s a mess.

Studies show, though, that TRT can decrease both visceral fat and body fat while improving BMI and waist size while increasing lean mass, which in itself dramatically reduces the risk of CVD.

Testosterone and Hardening of the Arteries (Atherosclerosis)

It doesn’t take a medical degree to understand that the internal plumbing of your cardiovascular system should remain free of clogs, and that’s essentially what atherosclerosis is. Lipids and a type of white blood cells accumulate inside the vessels, causing the vessels to lose elasticity and, in some cases, form blockages.

Doctors can measure the progression of atherosclerosis by measuring something called intima-media thickness (IMT) and an impressive number of studies have shown that there’s an inverse relationship between T levels and carotid IMT. In other words, the lower a man’s level of free testosterone, the more likely it is that his IMT is high. Low T often equals more gunked-up arteries.

In short, high levels of T seem to protect arteries from developing atherosclerosis.

Testosterone and Too Much Fat in the Blood (Dyslipidemia)

While the issue of cholesterol is controversial, it’s still considered to be one of the main risk factors for developing CVD. Several studies have, however, found a correlation between low levels of T and high levels of low-density lipoprotein (LDL), total cholesterol, triglycerides, and low levels of high-density lipoprotein (HDL).

TRT, though, has been shown to decrease the “bad” cholesterol (LDL), total cholesterol, and triglycerides. Likewise, TRT has been seen to increase “good” cholesterol (HDL), but a couple of other studies showed a slight decrease, while another showed no change at all.

Overall, though, TRT seems to help create a more favorable lipid profile, contributing to a potential decrease in CVD.

Testosterone and Blood Pressure

The factors that influence blood pressure are pretty complex. It’s essentially the relationship between the physical output of the heart and the resistance it meets through the vascular system.

Heart rate, strength of contraction, vascular tone, and levels of nitric oxide and endothelin (a peptide that causes blood vessels to constrict) are just a few of the things that influence this important barometer of cardiovascular health. Several studies, though, have shown T has beneficial effects on both diastolic and systolic blood pressure, as well as resting heart rate.

The Portuguese researchers even hypothesized that high blood pressure disorders seen in some pregnancies might some day be treated with androgens (testosterone or its close relatives).

Testosterone and Heart Disease

As I’ve pointed out, low T appears to be harmful to the heart due to its close relationship to various cardiac risk factors, but low T can also affect heart health directly. T levels seemingly affect the heart’s electrophysiology, vascular reactivity (tension, resistance, and blood flow through the venous system), and cardiac output (how efficiently it pumps out blood) itself.

Specifically, there appears to be an inverse relationship between T levels and coronary artery disease, or CAD. Low T levels are also associated with reduced heart function, including reduced left ventricular dysfunction.

As far as the electrophysiology of the heart, low T levels are a risk factor for arterial fibrillation, or AFib, although some studies have shown the opposite – that high or higher T levels are predictive of AFib. Of course, AFib also correlates with physiologically low levels of estradiol, too. As is often the case, more research is needed.

Should Testosterone be Used to Increase Heart Health?

Unfortunately, the FDA has only approved the use of testosterone to treat men with low testosterone levels who manifest symptoms of hypogonadism like decreased spontaneous erections, decreased libido, lack of energy, fatigue, shrinking testicles, and reduced levels of T as indicated by a blood test.

That’s too bad, because if the FDA and the medical profession had a more liberal attitude towards TRT, we might very well reduce the incidence of heart problems in this country by a bunch. Here’s a quick synopsis of some of the effects of testosterone that I touched on earlier:

  • TRT has been shown to reduce the mortality rate of men with Type 2 diabetes.
  • TRT has been shown to reduce fasting glucose levels, cholesterol levels, and obesity in men with hypogonadism.
  • TRT reduces fat mass in obese patients.
  • TRT has been shown to slow down the rate of atherosclerosis.
  • TRT has been shown to favorably affect blood pressure.
  • TRT has been shown to increase peak oxygen consumption during exercise.
  • TRT has been shown to increase cardiac output and reduce vascular resistance (making it easier for blood to flow through vessels).
  • TRT has been shown to play a protective role against stroke or myocardial infarction (heart attack).

Despite these impressive findings, it isn’t smart to regard testosterone or TRT as some sort of panacea regarding heart health. Heart disease is muy complex, and it’s difficult to find cardiologists who agree on anything, let alone the use of testosterone in making the heart healthier.

To muddy the cottonseed oil further, prescribing the precise amount of testosterone with which to bring about the healthiest heart possible is likely as much art as it is science. As such, we’re unsure whether to adjust T levels to “normal” or “high normal.”

Furthermore, everyone metabolizes the drug slightly differently, and how much testosterone remains free and how much is bound up by steroid hormone binding globulin (SHBG) or albumin, in addition to how much is aromatized into estrogen (which is itself a whole other topic regarding hearth health) is highly individual.

Unfortunately, the FDA’s restrictive stance is likely to prevent us from learning any definitive answers any time soon. All that being said, logic, along with my experience as both a long-time user and long-time researcher of testosterone, would suggest that men who use TRT aim for a free testosterone level between 20 ng/dl to 30 ng/dl, regardless of age.

Equally important (to hearth health, in addition to other health factors) is that they keep their estrogen levels between 21.80 pg/ml and 30.11 pg/ml. And, it certainly wouldn’t hurt to do all the usual heart-healthy things like exercise, get adequate rest, eat right, manage stress, and try to live somewhere where the air is fairly clean to breathe.

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References

Reference

  1. Lorigo M et al. Vascular Pathways of Testosterone: Clinical Implications. J Cardiovasc Transl Res. 2020 Feb;13(1):55-72. PubMed.
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No mention/update of/with TRAVERSE results?

Lmao. Good one! You stated it so stone cold. :joy:

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# Cardiovascular Safety of Testosterone-Replacement Therapy

CONCLUSIONS

In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034. opens in new tab.)

A study published in the Journal of the American Medical Association (JAMA) measured blood estradiol (a dominant estrogen) in 501 men with chronic heart failure. Compared to men in the balanced estrogen quintile, men in the lowest estradiol quintile were 317% more likely to die during a 3-year follow-up, while men in the highest estradiol quintile were 133% more likely to die.(24)

The men in the balanced quintile—with the fewest deaths—had serum estradiol levels between 21.80 and 30.11 pg/mL. This is virtually the ideal range that we have long recommended males strive for.

The men in the highest quintile who suffered 133% increased death rates had serum estradiol levels of 37.40 pg/mL or above. The lowest estradiol group that suffered a 317% increased death rate had serum estradiol levels under 12.90 pg/mL.

The dramatic increase in mortality in men with unbalanced estrogen (i.e., estradiol levels either too high or too low) is nothing short of astounding. It uncovers a gaping hole in conventional cardiology practice that is easily correctable.

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Excess aromatase robs men of their testosterone while exposing them to higher than desirable estradiol.(37) Aromatase can be suppressed with absorbable forms of chrysin (a plant flavonoid) and/or lignans such as those extracted from the Norway spruce tree (HMRlignan™).(38-42)

If these nutrients fail to reduce estradiol adequately, then we suggest that men ask their doctor to prescribe an aromatase-inhibiting drug like Arimidex® in the very low dose of 0.5 mg twice a week.

When aromatase is properly suppressed, estradiol levels are reduced to safe ranges, while free testosterone often increases, since less testosterone is being aromatized into estradiol.

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It depend on your interpretation of the data, men who are obese tend to have higher estrogen and suppressed testosterone.

I don’t think this applies to men on T replacement therapy.

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Interesting point. I need to dig out more of the research but this may be the sweet spot for dialing in anastrozole dosage. Up until now I have been a “only as needed for gyno” guy on AIs but perhaps it requires another look

That doesn’t seem very low IME. It’s would crash my E2 on TRT doses (probably, haven’t tried it, but 0.125 2x a week had me in single digits with 150 mg of test E a week).

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Very individual. Start MED. Some of these starting doses are sinister.

Start low / get some labs. Error bars on anastrozole dose response pretty wide compared to our fun Test dose response plot. Of course we know how to crush E2 but that ain’t the point.

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Agreed. And doctors are all over the board on dosages. One TRT doc I consulted says 0.5mg Arimidex ONCE per week is the right protocol.

Start VERY low. Test. Adjust as needed. This seems to be the right approach.

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And the advantage of being in the E2 “sweet spot” must also be weighed against the potential sides from Arimidex and relative dosage.

I know I definitely do not want to take Adex all the time.

I am a true TRT guy most of the time with Test 600-700 and E2 in the 40’s (slightly high for that test level but I’m OK with it and no sides). I guess this is considered my “cruise”.

But when I “blast” (2x per year, relatively low doses approx 3x TRT for 8-10 weeks) my E2 does get into the 60’s and 70’s so I am debating adding Adex on “blast” only. Again, I dont want to end up having to take it permanently and I dont think Adex has this effect (not a suicide inhibitor).

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Sounds like you and I are pretty similar in our approaches. I have my levels a bit higher on my TRT / cruise. I pull labs in the middle (not trough), but shoot for around 1000-1100 ng/dL TT.

I blast a bit less frequently than 2X a year (It’s been over a year, but thinking of doing one starting October), but they are typically a bit longer (more like 16 weeks). I’ll do between 2.5X and 3X my cruise (160 mg/wk).

The last blast was more than I am planning for this one. I did 875 mg/wk of Test E, and the last 5 or 6 weeks I did 40 mg/day of Tbol. I really like Tbol (for me it improves gym performance fairly noticeably), but I am thinking I’ll probably just stick with Test now. Just don’t want to stress the liver and kidneys, or destroy my lipid profile. I was also using Adex on that blast. I would pin EOD, and take 0.25 mg of Adex on the pin days. My E2 was 81 pg/mL (range =<29). I didn’t get any perceivable sides from that. I was also using finasteride at 0.5 mg/day, so E2 may have been higher than without that (most likely was). DHT was actually in range (high side) on that much Test.

Something to keep in mind is that E2 (and DHT) don’t have a linear response to TT or FT. It looks more like this (credit to @readalot for the graph):

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Very good data. The problem here is the chart is titled “Young Men” and unfortunately I am not :grinning: Estrogen has a tendency to creep up in older men as we know. I do bloods regularly (3-4x per year) so I can easily go by the actuals. It’s just a matter of deciding if I should be proactive against the E2 outside of any symptoms (to take advantage of the apparent aforementioned “sweet spot”) or just let it be. I am also wondering (since I have never used Adex but have it on hand) how much more usable T I would get out of my blasts if I chop down the E2.

BTW - I do occasionally add Oxandrolone in if I can get pharma (4 weeks max)

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@readalot has the chart for old men as well. I had it, but looked through my stuff and can’t find it. Perhaps he is willing to post it?

I don’t take Adex during TRT / Cruise personally. It does impact a few things like liver values, and IGF-1. On blast, I use it, but in a way that I am far from crashing E2. Just a bit of lowering since E2 will be quite high with high Test doses.

IIRC, ~10% of FT converts into E2 and DHT (might be ~10% each?). I think a similar portion of FT goes to each though.

It is well documented that 5AR blockers and AIs will boost Test numbers in naturals. IDK how much of that is from increasing the amount of testosterone actually produced though (an AI will impact the HPTA and the pituitary will produce more LH to increase Testosterone production) vs. limiting how much is converted to E2?

@mnben87 a little too kind. Thank Bhasin not me.

You can zoom in on the graphs with the link provided.

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