Testosterone made me feel 30 again — until it nearly broke my heart (Stat)

[RapamycinCurious]

@LukeMV

182mg per week is not that high of a dose. 75mg would be too low and defeat the purpose of taking it to begin with. 100mg is the minimum dose anyone should be on but I still think that’s too low for most. It’s not a one size fits all approach but 150mg is usually a good sweet spot for a lot of people.

You have a sampling bias. As the article notes, the Endocrine Society generally recommends replacement doses of 75-100 mg weekly for injections. The TRAVERSE trial, which was the definitive trial establishing cardiovascular safety for medically appropriate TRT, used gels rather than injection, but repeat-tested and adjusted the dose to maintain T between 350 and 750 ng/dL, which the great majority of men will achieve at these doses. Peter Attia uses 50 mg twice weekly for most of his TRT patients, and has never gone above 200 mg/week; Kevin White, who guided Matt Kaeberlein onto injected TRT, similarly uses 50 mg twice weekly in nearly all cases.

@LukeMV

@RapAdmin

• Hematocrit >54% → therapy should be reduced, paused, or discontinued.
• Hematocrit >50–52% → many clinicians begin dose adjustments or closer monitoring.

This part is barbaric. The fact the guidelines still say in the year 2025 say you need to discontinue TRT once the hematocrit % reaches the magic number of 54% is a disastrous medical practice, especially since it’s more than likely because the doctor didn’t tell the patient that he needed to drink water before the blood draw.

Read the actual passage. The guidelines do not say that you need to discontinue TRT once the hematocrit reaches the magic number of 54%: they say you should begin close monitoring and make adjustments when it reaches 50-52%, and that therapy should be reduced, paused, OR discontinued if it continues to climb above 54%.

@Thorin

@A_User

@LukeMV

There is only one study showing a slight short term increased risk of MACE among TRT users with hematocrits above 52% (5.15% increase compared to 3.87% in normal hematocrit people).

I think he mentioned heart failure though and not MACE.

I asked Google “Is heart failure one of the elements of MACE in cardiology”. Here is part of the answer I got.

Yes, heart failure is often included as one of the elements of Major Adverse Cardiovascular Events (MACE) in cardiology. The exact components of MACE can vary between different clinical studies, but heart failure is a common and serious outcome frequently monitored.

Read original sources. Google makes free use of unreliable sources that get a lot of clicks, hallucinates, and tells you what it thinks you want to hear.

There are studies that use heart failure as part of MACE, but they’re rare: usually, MACE means MI, stroke, or cardiovascular death, and sometimes extends to revascularization and/or unstable angina.

In this case, we don’t have to guess: just follow the link that LukeMV provided to the study in question and then retrieve the free full text.

“MACE were defined as a composite of death from any cause, MI (I21–I23) and stroke (I63, G45). VTE included deep vein thrombosis (I82 and Z86.718) and pulmonary embolism (I26).”

Including all-cause mortality under MACE is a highly unorthodox maneuver, but (a) it’s not heart failure, and (b) that implies that the risk of overdoing it on TRT might be higher than the abstract implies. “However, MACE/VTE subset analysis revealed an increased risk of developing acute MI (OR 1.81, 95% CI 1.2–2.7) and VTE (OR 1.51, 95% CI 1.17–1.94) in the men with polycythemia. However, the risk of death (OR 1.14, 95% CI 0.78–1.65) or developing a stroke (OR 0.91, 95% CI 0.64–1.29) was similar.” That’s a bit reassuring on death, though it’s not clear they are powered to rule it out.

[LukeMV]

@RapamycinCurious

You have a sampling bias. As the article notes, the Endocrine Society generally recommends replacement doses of 75-100 mg weekly for injections. The TRAVERSE trial, which was the definitive trial establishing cardiovascular safety for medically appropriate TRT, used gels rather than injection, but repeat-tested and adjusted the dose to maintain T between 350 and 750 ng/dL, which the great majority of men will achieve at these doses. Peter Attia uses 50 mg twice weekly for most of his TRT patients, and has never gone above 200 mg/week; Kevin White, who guided Matt Kaeberlein onto injected TRT, similarly uses 50 mg twice weekly in nearly all cases.

The TRT guidelines are a joke and always have been. Testosterone dosage paranoia does much more harm than good. A 75mg once weekly trough with leave many men under the lab range, which was created for an unheathy population and leaves people with symptoms despite being “in range.”

The guidelines are so much of a joke that they still recommend people inject with the really long needle instead of an insulin needle. They also say it’s ok to inject every two weeks.

[austin242]

Any evidence for this (that the TRT guidelines are wrong)?

[LukeMV]

I think the better question is if there is any evidence that they’re right and where did they come up with the guidelines to begin with

[RapamycinCurious]

@LukeMV

The TRT guidelines are a joke and always have been. Testosterone dosage paranoia does much more harm than good. A 75mg once weekly trough with leave many men under the lab range, which was created for an unheathy population and leaves people with symptoms despite being “in range.”

This is inaccurate. The guidelines are based on randomized, placebo-controlled dose-escalation studies with achieved serum T and symptomatic effects, not pulling dose levels out of their tushes.

To pick an extreme example, in PMID: 22396515, “we suppressed endogenous testosterone by administering a long-acting gonadotropin-releasing hormone agonist, and created different levels of circulating testosterone concentrations by administration of graded doses of testosterone enanthate.” So before these guys were given T, their endogenous T had been knocked down to zero, rather than having 200-300 ng/dL already in the tank.

Then “[H]ealthy men aged 18 to 50 years …received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups).” Focusing on the lower two T doses as being in the ballpark of the guidelines: in the groups given T plus placebo, “the mean [on-treatment] testosterone level was 385 ng/dL (95% CI, 261-508 ng/dL) for 50 mg/wk, 822 ng/dL (95% CI, 658-986 ng/dL) for 125 mg/wk”; for those on T + dutasteride, “the mean testosterone level was 519 ng/dL (95% CI, 378-660 ng/dL) for 50 mg/wk, 895 ng/dL (95% CI, 616-1173 ng/dL) for 125 mg/wk”.

So more than half of men can get within the normal range even at 50 mg/week, and very nearly all of them do at 125 mg/week, even after reducing endogenous T production to ZERO.

[Davin8r]

@RapamycinCurious

more than half of men can get within the normal range even at 50 mg/week

The other main argument I frequently see is that “normal” isn’t necessarily “optimal”. If “normal/average” is based on a population of generally overweight/obese American men, is this what we really want to aim for? If managing potential side effects (blood pressure, hematocrit, excess estrogen, high DHT, etc), can a man get more of a benefit from higher T, at least on the higher side of the “normal” range? I think this is what many of us would like to believe, but it takes more work than just shooting for a total T of 800 and calling it good (less potential side effects, less potential benefit?).

[LukeMV]

As I mentioned, the lower end of the range is fraudulent and no evidence of harm exists at a testosterone level of 1000 for men on TRT

@Davin8r

The other main argument I frequently see is that “normal” isn’t necessarily “optimal”. If “normal/average” is based on a population of generally overweight/obese American men, is this what we really want to aim for? If managing potential side effects (blood pressure, hematocrit, excess estrogen, high DHT, etc), can a man get more of a benefit from higher T, at least on the higher side of the “normal” range? I think this is what many of us would like to believe, but it takes more work than just shooting for a total T of 800 and calling it good (less potential side effects, less potential benefit?).

Exactly, except I wouldn’t manage excess estrogen.

[RapamycinCurious]

@Davin8r

The other main argument I frequently see is that “normal” isn’t necessarily “optimal”. If “normal/average” is based on a population of generally overweight/obese American men, is this what we really want to aim for?

The standard reference ranges and guideline targets are consistent with healthy nonobese men aged 19 to 39 from the US and Europe.

[Davin8r]

Non-obese is a good start, but average male testosterone levels have been declining in a linear fashion since at least 1970, independent of BMI:

Temporal trends in serum testosterone and luteinizing hormone levels indicate...

[RapamycinCurious]

@Davin8r

Non-obese is a good start, but average male testosterone levels have been declining in a linear fashion since at least 1970, independent of BMI:

Fair — but in addition to being nonobese, these men were healthy (free of enumerated diseases and metabolic dysfuntions). Also, these data come from baseline data on men in cohort studies from a while back: FRS was from 1998-2005, EMAS was from 2003–2005, etc.

[RapAdmin]

@Davin8r

but average male testosterone levels have been declining in a linear fashion since at least 1970

There seems to be some conflicting evidence on this topic… I’m not sure which data is better:

Source: https://x.com/aditharun_/status/1980357420657393832

[AustraliaLongevity]

They’ve lowered the low and high end of the reference range multiple times. Men with testosterone that would previously have been flagged as low are now “low normal”. If they have symptoms they need to fix it or treat it.

[LukeMV]

Exactly. Treating the symptoms should take priority over the numbers. If someone has a lower level within the range but claims to feel good, then ok fine don’t treat if they don’t want to. But if it’s low end of normal with symptoms, then they should have the option to treat.

[RapamycinCurious]

@RapAdmin

@Davin8r

but average male testosterone levels have been declining in a linear fashion since at least 1970

There seems to be some conflicting evidence on this topic…

This isn’t really contradictory: Dr. Arun is noting the effects of an assay change over the last decade, not going all the way back to the 70s.

Additional possible factors relevant to the last two decades: rising use of steroids and non-indicated TRT in younger men, leading to persistent hypogonadism, and rising rates of opioid (ab)use, which suppresses T by nearly 50%.

[Davin8r]

@RapamycinCurious

rising use of steroids and non-indicated TRT in younger men

Non-indicated TRT would tend to increase average testosterone, not decrease it (unless for some reason they stopped the TRT prior to the blood test, which wouldn’t make sense). I’m more suspicious of environmental factors such as plastic-based chemicals, etc.

[LukeMV]

This is very interesting. Someone asked Grok if that was true in the thread and Grok said it was a good theory. To be honest, I am not surprised. I think low testosterone is largely a product of obesity anyway and to a lesser degree, environmental factors.

Side note, I love how you can ask Grok in a thread on X if the original tweet’s claims are true. It holds people accountable for what they say.

[RapamycinCurious]

For the purposes of establishing reference ranges, “they” don’t measure T levels in people on TRT: that would defeat the purpose. But if you’re a young man who’s been on steroids and non-indicated TRT, yo’ure at risk of , persistent hypogonadism, bringing the population average down.

[Davin8r]

@RapamycinCurious

But if you’re a young man who’s been on steroids and non-indicated TRT, yo’ure at risk of , persistent hypogonadism, bringing the population average down.

So you’re speculating that a population of men who used to be on TRT or other steroids, then stopped and have persistent untreated hypogonadism, is large enough of a group to bring down the average measured T in the general population?

[AustraliaLongevity]

That is statistically insignificant and not the issue.

[RapamycinCurious]

I agree that this is a much smaller contributor than the overwhelming effect of the obesity epidemic (yes, I recognize we’ve both referenced studies in nonobese males) and the smaller but non-trivial effect of opioid use and abuse.