Testosterone and Cardiovascular Disease

Pharma / TRT Testosterone Replacement
1

Someone posted this in another group and I wanted to share it here.

A review by Goodale et al. (2017) on testosterone and cardiovascular disease.

Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men.

Two recent observational studies reported increased CV risks
in men who received testosterone prescriptions.17,18 Although they gained a significant amount of media attention, neither study pro- vided credible evidence of increased CV risk. In one study, Vigen et al. made an official correction for misreporting their primary results, which actually showed a lower percentage of adverse CV events in the T-treated group compared to untreated men.19 In the other study, Finkle et al. had no control group, so it is unknown whether CV events differed between treated and untreated men with TD.19 The U.S. Food and Drug Administration (FDA) re- viewed the CV safety of T products shortly after publication of these articles. In its assessment of CV risks and T therapy, the FDA identified a total of only 4 studies suggesting an increased risk,
yet none provided solid evidence to support this. By comparison, more than 100 studies have reported reduced CV risk with high-
er endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent TRT versus untreated men.19 Two recent studies in men who received TRT found reduced CV events in those whose follow-up T level normalized compared to men whose T concen- tration remained low.20,21 Another large observational study noted that T therapy was associated with reduced risk of myocardial in- farction in men in the highest risk category.22 A recently published meta-analysis of 75 placebo-controlled studies, the largest to date, found no evidence of increased CV risk with T therapy and clear evidence of improved metabolic profiles.23 An international expert consensus regarding testosterone deficiency and treatment, pub- lished in the July 2016 Mayo Clinic Proceedings, concluded: ā€œThere is no credible evidence at this time that T therapy increases CV risk and substantial evidence that it does not. Indeed, there is

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Here is one snippet that is very important

the FDA identified a total of only 4 studies suggesting an increased risk,
yet none provided solid evidence to support this. By comparison, more than 100 studies have reported reduced CV risk with high-
er endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent TRT versus untreated men

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Great read regarding This topic

http://www.onlinejacc.org/content/accj/67/5/545.full.pdf

Hereā€™s snapshot

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image750Ɨ1153 258 KB

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image1334Ɨ750 144 KB

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Dude thats nothing just inject more. No ais.

:slight_smile:

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Exactly when we look at the info we realize majority of studies that say T causes CV events we realize how much nonsense is being fed to the world.

This is frustrating as F.

And then they keep comparing T with men over 65. People who have a history of CV illness and etc

This is obvious manipulation by someone who doesnā€™t want T to become popular.

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Huh?

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The report I posted is quite positive for TRT and cardio health.

Itā€™s a report that analyzed many studies

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Yes I know and love it. I still hate how people choose negatives but not the positives like these

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@enackers @charlie12

First and foremost, I am pro TRT as the benefits of TRT by far outweighs the risks in most patients.

However, as somebody who is actively doing research and drug development for now almost 20 years and published >35 articles in journals like Cell and Nature let me make one comment which is generally applicable in science:

The absence of evidence doesnt mean that there is evidence for the absence.

Up to now there isnt a single powered and well controlled prospective study available which demonstrated the absence of increased cardiovascular risks following long term (10 years) use of TRT.

This is why two of the latest articles recommend to perform a prospective randomized trial.

Kloner et al, 2017 (the one you shared)
A proposed study to definitively answer the question of whether TRT has adverse effects on CV safety is needed. It should be a large, prospective, randomized, placebo-controlled, double-blinded, long-term study (at least 1 year and preferably longer).

Gagliano-Juca & Basaria, Nature Cardiology Review 2019
Meta-analyses of randomized, controlled trials of testosterone replacement therapy report conflicting findings, probably because the included trials lacked power or the duration was too short to assess cardiovascular events.
The TRAVERSE trial, the first trial of testosterone therapy that is adequately powered to assess cardiovascular events, began in 2018, and its findings might take a decade to become available.
Until the results of the TRAVERSE trial are available, clinicians should individualize testosterone treatment after having an informed discussion with their patients about the risks and benefits of testosterone replacement therapy

Until data from such a study are available one can only conclude that TRT appears to be safe and effective but definitely not that TRT has been demonstrated to be free of cardiovascular side effects.

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Being on TRT I read a lot. I get regular cardio check ups. We get labs that check all sorts of stuff. This can play a big role in our health compared to the general population.

And I bet you most of us are the same being on TRT.
We are on top of our health.

For example I have mild cardiomyopathy that is being treated. Had I not been on TRT perhaps I would not have gotten that echo.

I just did genetic testing. So will soon find out more.

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Obviously you are correct and I totally agree, but logic prevails and itā€™s clear that we have nothing to fear with therapeutical HRT. With the info we have. Men need T. Men with low t have illnesses galore. Give a man healthy levels of T and they should reverse the low t symptoms. What levels you choose is another discussion. This is a simple observational truth and I cannot see how it would be wrong.

What we are saying here is that the nonsense trt causes CV issues is wrong and the studies are poorly made. People run around giving blood and keeping their dose very low out of this fear. doctors neglect their patients health because they think trt causes death. This is based ok studies which are faulty and full of holes . More than anything the observational evidence we have is strong enough to reinforce the use of trt in patients who need it for longevity and quality of life.

Also we have to wonder why would somebody make a study and purposely skeew the outcome to show trt is harmful? Thereā€™s something else going on here. Someone is in somebodies pocket.

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Why do you think somebody would on purpose try to skeew the data? Yes, studies have been done on patient groups which might (!) not reflect the situation of a 40 year old with unknown causes of low T. Subjects older than 65, subjects with limited mobility, subjects with liver disease or chronic disease (eg HIV positive). But do these patients group not also have the right to be studied? What if especially in ā€˜oldā€™ patients with limited mobility the outcome would have been, that T cuts their risk of heart disease into half? What if the outcome in studying HIV positive men shows improved immune function?
Yes, many of these what you call ā€˜faulty and full of holesā€™ studies are then included in so called meta studies, which combine many studies to increase statistical power. And thats why subanalyses are performed in metastudies, or thats why the inclusion criteria is defined. Its to be able to differentiate the cardiovascular risk between patient groups (old vs young, healthy vs chronic disease, injectables vs gel etc).
This is a very important aspect in the ongoing discussion. When studies show ambiguous results the reasons are mostly either a lack of statistical power (if you assume a 5% higher risk of lets say stroke on TRT you need a lot of patients to reach statistical significance) or differenf patient groups have a different risk profile. And thats what seems to be ongoing.

ā€˜Oldā€™ patients seem to respond differently than ā€˜youngā€™ ones, but arent we all getting old. And if at older age ths risk is different to non treated do the benefits that you get before 65 (random number) outweight the risks once you reach your 60s? We dont know.

An interesting study looked at the risks associated between the different application forms, patches, creams/gel an injections. They found a signigicant higher risk for creams/gels in comparison to injectable T. Theory is that DHT is the main modulator of risk. Thats the type of data that we need.

TRT studies are either run by pharma companies or mostly by academic institutions. Academic institutions do not have any interest in skeewing any outcome, why woukd they. Pharma is interested in positive study outcomes. A single clinical phase III trial can easily cost >50 millions so there is no interest in wasting the money by trying to get a negative outcome. And pharma is strictly regulated by health agencies. Inspections are performed before every approval (eg last one Xyosted) and these inspections are tough. You need to be able to explain every data point of every patient, everything needs to be traceable down to the temperature of the cold room where the samples have been stored before analysis.

Testosterone prescriptions have tripled in the last years and the prevalence in the US is around 2 to 3% now. Thats a high number having an impact on a population as such. Imagine eg US FDA clears all warnings on T products for potential CV risks on the basis of the now available data and in 10 years from now this ongoing prospective T trial demonstrates a 10% higher risk for CV events. Everybody would go crazy in 2029 and blame the agency for not taking care of the US patients and for being on the side of pharma, when the data in 2019 showed ambiguous results. Remember the absence of evidence doesnt mean there is evidence for the absence.

You say T is necessary for men. Correct. Beta carotene as a precursor of Vitamin A is essential for humans. Beta carotene is also an antioxidant thats why it was studied in the CARET and ATBC study for its preventive potential in smokers. Initial studies with short duration and surrogate markers of lung cancer development were promising. So a total of around 50000 smokers were given 20 or 30 mg beta carotene per day for 5 to 8 years. The results were surprising and shocking, patients receiving beta carotene had a significant higher risk for developing lung cancer than the non treated smokers.

The probability that TRT could be the same story is low, but nevertheless it shows that the absence of evidence is not the same as the evidence for the absence.

If I was a patient not interested in all of this I nonetheless would appreciate the notion of a small potential risks than learning in 10 years that data would have showed a potential small risk but nobody told me. As an adult I am able to handle this and make a decision.

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How long have you been doing trt or are you even on trt? How many doctors have you spoke To ? Under scrutiny because they give T to a man whose 30 with in range numbers. We all know men that are younger have higher hormones yet today they are told itā€™s not a problem because their 350ng is in range.

Lab companies are lowering our numbers to keep us at lower ranges based on a sick population and studies that ouright clarify these new ranges are based on a sick pop of unhealthy Obese diabetic men.

Iā€™m lost how you can think this is all in the name of being professional and health.

Ifs an obvious threat and people skewing the data.

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Itā€™s more profitable to treat disease rather than prevent it. TRT can take a bite out of expensive medicine like viagra or cialis, TRT can treat the problem and no drugs needed. TRT will also prevent disease as well taking more profit away from big pharma.

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Now we are in the land of conspiracy theories.

Yes I am on TRT. Several years on different flavours of TRT with interruptions (Clomi, hCG+FSH, now T enant).

We are confusing safety and efficacy. What you mentioned is not related to safety but to efficacy of TRT.

Can you provide evidence for your statement ā€˜new ranges are based on a sick pop of unhealthy Obese diabetic men.ā€™?

Reference ranges are based on healthy non-obese subjects. Thats stated in every scientific publication on reference ranges as well as on the lab reports (reference range based healthy nin obese men between 19 and 39 years).

Can you please provide evidence that the reference ranges were lowered over time (consider testing methodology). What do you mean by ā€˜Lab companies are lowering our numbers to keep us at lower rangesā€™? Can you provide any evidence for this statement?

Whether testosterone is declining on a population level is a controversaly discussed topic. Travison et al 2007 described a decline in testosterone on a population level, whereas Nyante et al, 2012 concluded that there is no evidence for a decline in US men. Andersson et al, 200i have describes a decrease in SHBG and total T but no change in freeT levels between 1982 and 2000.

Studies have shown that still about 35% of men with a freeT of 5 ng/dl do not have any symptoms of androgen deficiency. Its not black or white, there is no generally applicable clear threshold below all men will develop symptoms of androgen deficiency.

@systemlord
With your history that you discuss on this forum its beyond my understanding that you think TRT has only benefits. Its has excarabated your underlying disease and finally brought you to the ER with a serious condition. Recently you stated here that you dont need TRT because you now identified the underlying cause to be diabetes.

Prevention starts with life style decisions like exercise and diet, its on you to modify these factors so that you dont need the assistance provided by the pharma business. On a population level we see an epidemic of obesity, diabetes and liver disease that all have an impact of wellbeing and testosterone. Once you need it (and I am also an example of this) you need to balance the benefit to risk ratio.

Both of you are blowing generalized statements into the air without any qualification or evidence beyond your personal opinion. And I think thats problematic for the people joining this forum in the search of general science based support or - if declared as such - for personal opinions and experience.

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I think most understand these are all opinions and personal experiences. Even if I see an MD after someoneā€™s name.

If a user reads something on here and accepts as medical adviceā€¦ the problem is that user.

Btw my opinion is. Lol. I agree with your post And opinions except for the part I mention above.

Apparently there are many men on TRT that donā€™t have any issues. Perhaps the ones that do and canā€™t seem to dial in have undiagnosed disease or are not true hypogonadal.

Of course this is my opinion but I donā€™t think itā€™s necessary for me to state that in every post for some idiots out there.

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You have lost it man. Who do you work for the insurance company or what?

I have numerous studies showing why this new 900 lab range is 900 and not 1200.

Add your email. I will forward a dozen studies showing so.

  1. Author created a study to show men have lower T levels today than in the past. He found a massive huge drop. He stated this was due to the environment health and etc

  2. The new lab ranges were lowered and this study was used as the basis for that lowering.

The same studies were used. They are actual studies man.

No itā€™s not a conspiracy therory itā€™s truth and for you to come in and act like everything is fine and dandy and men are being given a fair shake is beyond me. Are you a man or a woman? If you are a man you should be outraged.

Tell me one more thing. T levels maxed out 1200 a couple years ago. A decade ago they were 1500. Today 900?

Tell me again how there is something of a conspiracy going on.

Do you really think they go test a thousand healthy men to see where their T levels are at?

No they do not.

@charlie12

What I say is truth. I am amazed how yā€™all can sit there and think this is not wrong and everything is ok.

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This is a waste of time. Instead of trying to understand what Iā€™m saying you are coming up with other topics.

So you are telling me that today 900 is based on a healthy population of men?

That if you were having a level of 1100 7 years ago, today you will lower It to 900 because your doc doesnā€™t want you going above range.

Letā€™s use logic here and stop all this complicated picking apart and try to understand what Iā€™m saying without veering off into other areas.

I donā€™t care if 5ng has not shown AD in men. We are not talking about that: we are talking about TRT.

The question should Also be ā€œwhy are men with so called normal ranges showing symptoms And need treatmentā€. Not the opposite. Good for them.

Why are men being told their doses are too high when that same lab range showed they were under the max level last year or the year before.

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Just provide the evidence instead of repeating the same statements.

There is nothing wrong in having different opinions, as long as statements are backed up and a discussion is held in a respectful way.

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This is correct, I started TRT and did fine for a while, but because I was improperly diagnosed problems were encountered. If to take an otherwise healthy man with no medical problems TRT will show benefit, but if the guy has a clotting disorder or undiagnosed heart problem, there will be consequences.

Just yesterday I read an article about a government employee who had live a sedentary lifestyle and sat all day at work and was hugely obese at 41 years old, he went on TRT and had a heart attack and blamed TRT and this clinic for his heart attack and not his shitty lifestyle.