6 ms·

Interesting. Saying, "there may not be a safe off-ramp," doesn’t feel quite right. The article describes people losing weight while on the drugs and then regain

by tyleo 11mo ago

Interesting. Saying, "there may not be a safe off-ramp," doesn’t feel quite right. The article describes people losing weight while on the drugs and then regaining weight after stopping them. That's not ideal, but it does imply an off-ramp, just with regressions. Compare that to something with no real off-ramp: testosterone replacement therapy. Once you're on TRT, you can permanently suppress your body's own testosterone production, and many men won't produce enough on their own afterward.

gtirloni 11mo ago
If you're on TRT, you are already not producing enough on your own.
- tortilla 11mo ago
  Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol* * not me but I see it with men in my age range
  - PartiallyTyped 11mo ago
    I am a big fan of Dr Rohin Francis, and this landed on my youtube's front-page recently https://www.youtube.com/watch?v=FPsKTfFQFqc https://www.youtube.com/watch?v=FPsKTfFQFqc
  - Aurornis 11mo ago
    I’m getting downvoted in another comment for saying this, but it’s a growing problem. In some surveys of TRT patients up to 1/4 of them didn’t even have their testosterone levels measured before being prescribed TRT. The men’s health clinics are finding excuses to diagnose everyone who calls. The lifetime value of a monthly TRT customer is very high.
  - chimeracoder 11mo ago
    > Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol Saying that the men's vitality clinic "pushed you" into a treatment protocol is like saying that a fertility clinic pushed you into getting pregnant. Sure, it's a common outcome, but you had an idea of what you wanted out of it before you walked in the door.
    - dragonwriter 11mo ago
      > Saying that the men's vitality clinic "pushed you" into a treatment protocol is like saying that a fertility clinic pushed you into getting pregnant. No, it isn't. “Men’s vitality” doesn’t mean “getting pumped with testosterone regardless of indications” the way “fertility” means “getting pregnant” in either literal denotation of words or the understanding of the general population. > Sure, it's a common outcome, but you had an idea of what you wanted out of it before you walked in the door. Yes, but in the case of fertility clinics, getting pregnant aas definitely the outcome beinf sought. Being pumped with testosterone isn’t the outcome being sought from a men’s vitality clinic, it is (even for the people who are actively thinking about it) a mechanism (and not an appropriate one for every patient) for atteempting to acheive the desired outcome. If you go to a fertility clinic and they don't attempt to identify the source of your fertility issues and just pump you with hormones not indicated for your specific issue, that would be wrong, too.
      - chimeracoder 11mo ago
        > No, it isn't. “Men’s vitality” doesn’t mean “getting pumped with testosterone regardless of indications” When I Google "men's vitality clinic", the top result I see is titled "Your experts for testosterone replacement therapy...". TRT is front and center. > Being pumped with testosterone isn’t the outcome being sought from a men’s vitality clinic, it is (even for the people who are actively thinking about it) a mechanism (and not an appropriate one for every patient) for atteempting to acheive the desired outcome. This is such a weird distinction to try and make. I frequently see ads for these services, and even when they're not so explicit as that one is about what they're selling, it's extremely clear what demographic they're going after and what the hook is. Testosterone being a Schedule III substance, "men's vitality" is the way that they can legally advertise an service that prescribes AAS. It's no more of a secret that men's vitality clinics prescribe testosterone than it is that fertility clinics are prescribing estradiol. Both of these are sex hormones that induce a specific effect on the body which the patient is looking for. Can I imagine someone walking into a men's vitality clinic and being surprised that they're getting offered testosterone? Sure, and there's also that German couple who went to a fertility clinic because they weren't having a baby, and were surprised to learn that they needed to start having sex. Clueless people exist. That doesn't mean that it's not readily obvious to anyone who's paying attention what these clinics exist to do, and how they do it.
- Aurornis 11mo ago
  Unfortunately that’s not true any more. TRT over prescribing is a major problem right now. Studies of TRT patients have even shown that 1/4 of TRT patients may not have had their testosterone levels measured before being prescribed TRT: (Source https://pmc.ncbi.nlm.nih.gov/articles/PMC6406807/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6406807/ ) Completely unacceptable given how cheap testosterone testing is, but its happening. TRT clinics have also become a big business. Their business model relies on prescribing TRT to anyone and then charging them monthly or quarterly to continue receiving those prescriptions, which as the parent comment noted become physically necessary after TRT causes the testes to atrophy. The trick the clinics are using now is “diagnosing by symptoms”. They have a long list of “symptoms of low T” and the patient is basically prompted to check off enough boxes to justify TRT. It’s the same model as the medical marijuana card businesses where you can go in and the doctor will “find” a reason to give you the prescription. It’s a real problem when combined with social media influencers who tell people that everything is a symptom of low testosterone and TRT will fix it.
  - gadders 11mo ago
    >>The trick the clinics are using now is “diagnosing by symptoms”. You can't really diagnose by levels, though, unless you knew what that person's previous levels were. Setting an average across a population is not really realistic - you can't say Shaq should work to the same levels as, say, Emo Phillips. TRT is normally used due to aging, though, so you are unlikely to have your testosterone levels spontaneously recover as you get older. You do tend to need to be on it for life, in the same way that women stay on HRT. However, if you did need to get off, bodybuilders have "post cycle therapies" to kick start production so it seems to be possible.
    - Aurornis 11mo ago
      If someone shows up with a testosterone level of 700 you can (and should) explain that low testosterone is not the explanation for whatever they’re suffering from. The TRT clinics are ignoring levels or even not testing at all. They’ll find an excuse to prescribe to someone even who has clinically high levels because they want the monthly recurring revenue from keeping that customer for life.
- theptip 11mo ago
  But TRT suppresses endogenous production further, so if you go off it you’re worse than when you started.
- asafira 11mo ago
  Isn't there TRT that doesn't impact your endogenous production? (HCG, SERMs)
mise_en_place 11mo ago
By what mechanism? That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The question is, why would someone with clinical hypogonadism cease TRT?
- Aurornis 11mo ago
  > That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The testes atrophy over time when LH and FSH are suppressed. Even if LH and FSH return (which isn’t guaranteed) the testes need to be able to respond to those hormonal signals, but atrophied testes do not respond the same. For someone with true intractable hypogonadism this hardly matters because they weren’t capable anyway. Many people prescribed TRT today don’t actually have intractable hypogonadism, though. Body builders have some tricks to try to reverse this, but it’s not perfectly effective and even body builders know to cycle their steroids to avoid having prolonged periods of suppressed HPG axis activity. I was involved with weightlifting in my younger years but never dabbled with steroids or TRT. Everyone I know who did try testosterone or steroids thought they were doing it the safe way (HCG, PCT, limited cycle length) but became unable to produce enough endogenous testosterone by their 40s even with SERMs. Men on TRT for years will have considerable testicular atrophy that is not totally reversible. > The question is, why would someone with clinical hypogonadism cease TRT? TRT is no longer limited to men with clinical hypogonadism. Men’s health clinics that advertise on social media, TV, and radio will prescribe to anyone who contacts them (and pays cash for the prescription and gear). In some surveys of patients on TRT, 1/4 of patients didn’t even have testosterone levels measured prior to initiation of TRT.
  - mise_en_place 11mo ago
    > TRT is no longer limited to men with clinical hypogonadism. Men’s health clinics that advertise on social media, TV, and radio will prescribe to anyone who contacts them (and pays cash for the prescription and gear). In some surveys of patients on TRT, 1/4 of patients didn’t even have testosterone levels measured prior to initiation of TRT. That's hugely problematic if true. They should be investigated and if found of wrongdoing, have their medical licenses revoked.
sReinwald 11mo ago
Strange framing, isn't it? Bariatric surgery shows 25-65% significant regain rates depending on definition and timeframe. And regular dieting is even worse. Nobody would frame that as a safety issue. That's... just how weight loss works, not a unique GLP-1 problem. Calling a return of symptoms (obesity) a "safety issue" is like saying insulin has "no safe off-ramp" because diabetics get hyperglycemic when they stop taking it. Fear gets clicks, I guess.
- csense 11mo ago
  At some point, somebody at the site changed the title. The old title was "GLP-1 Drugs Improve Heart Health, But Only If You Keep Taking Them." How do I know that? The URL slug tells the tale. > Fear gets clicks, I guess I strongly suspect this is the reason the title was changed.
  - Thegn 11mo ago
    I know they (Ars Technica) do A/B title tests sometimes from discussion with one of the people who works there.
  - cauliflower2718 11mo ago
    The original title is so much more informative. It might be so informative that many people didn't feel a need to read the article.
- bsder 11mo ago
  It's also very strange because more than 75% had some level of sustained weight loss after several years. That's way better than any other weight loss program. Nothing else even comes close.
- m463 11mo ago
  well, it could also be from a "do no harm" standpoint. (although looking into it, it seems many oaths never actually say "first do no harm")
taeric 11mo ago
Yeah, I would fully support "easy" there, but regaining weight isn't something most people think of as danger.
- fwip 11mo ago
  Many people who are losing weight are doing so because they're concerned about their health, right? Especially heart health.
  - taeric 11mo ago
    I mean, sure? But this is like saying there is no safe way to get old. Which, is kind of accurate. But not what people think of when you say safe.
financltravsty 11mo ago
As an experienced polysubstance researcher, that's not exactly accurate. TRT cessation does not inherently cause men to have suppressed hormone levels after. With precautions and extra steps like HCG to maintain leydig cell/testicular function, preventing atrophy, one may safeguard against that risk. Coming off TRT, yes you will have lower levels as your HPTA has been suppressed by exogenous hormones. One may speed up this recovery using "PCT" (post cycle therapy), which involves taking a SERM (selective estrogen receptor modulator, e.g. enclomiphene) to resensitize and restart your HPTA. However this is not always necessary, and if one takes a look at the HARLEM study, most users return to their baseline levels within a year of going cold turkey. In the cases of true permanently lowered levels of hormones, I believe the two most common reasons are: using other AAS besides testosterone (1) and lifestyle or health factors that correlate with the need to be on TRT (2). With 1, this can be seen in users of decadurabolin (deca), which notoriously has hormone receptor active metabolites that last around for atleast a year, continuously suppressing the system. Or trenbolone (tren/cattle bulking hormone) which is inherently neurally and endocrinically otherwise toxic. With 2, you hop on TRT because there is some reason your hormones are not at healthy levels. Whatever the reason is, it is still there, and once you've stopped bandaiding the issue its effects resurface. --- I have also used many GLP-1s (semaglutide, tirzepatide, and retatrutide). No there is no off-ramp, but the only effects I've noticed are a return to my baseline of appetite, and neurological state. N.B. GLP-1s are good for impulse and behavioral disorders like ADHD, which it did help. However, I have decided to not take it due to the negative effects on personality and reward seeking behavior. They are neuro-active in the brain, and their effects I've decided are not worth it.
- tyleo 11mo ago
  This reasoning is not flowing through for me. It feels like you are saying: 1. There is an off ramp for TRTs but some people have, “true permanently lowered levels of hormones.” 2. For GLP-1s, “there is no off-ramp, but the only effects I’ve noticed are a return to my baseline.” To clarify my original post, I consider the ability to return to baseline to mean there is an off-ramp and permanently impacted to mean there is no off-ramp.
  - 11mo ago
observationist 11mo ago
"Those poor people have no agency and their behaviors are outside their control!" Well, I guess we have no choice but to affirm and reinforce their lack of agency and ensure we put them on drugs for the rest of their lives! It's ironic that one of the effects of this drug seems to be reducing the impact of impulsive behaviors, reducing cravings from other drugs and alcohol and cigarette addictions. The hat trick for someone might be to get on one of these GLP-1 regimens, wean themselves out of whatever crisis/crises they are in, end their GLP-1 regimen with a heroic mushroom trip, and physically move to a new environment, where they don't have any of the default triggers or patterns to fall back on, and everything is fresh and can be built up from scratch. I think the medicalization of human agency is one of the great evils of our time. The implication and impact of doctors, bureaucrats, and bean counters making sweeping policy, regulation, and legal decisions on behalf of the peasants and peons who just don't know better. The casual dismissal of fundamental basic principles is outrageous, especially in service to the politics and idiotic tribalism.
- acuozzo 11mo ago
  > "Those poor people have no agency and their behaviors are outside their control!" Our complex modern society has a daily buy-in. Some people were born and/or raised for it and the cost for them is nothing. Others need to soothe the pain of shoehorning themselves into it by chain-smoking while working a jackhammer or shoveling cereal into their face while programming. Yes, these behaviors are technically within their control, but are you really going to suggest that we can solve the underlying problem(s)?
- BizarroLand 11mo ago
  I think your opinion is valid from your point of view but missing an important part of the bigger picture. Obese people typically do not try to become obese. Most obese people have tried to lose weight and find that they lack the tools and skills needed to succeed, and many of the ones that do succeed only do so temporarily. Why is that? It's a question with no simple answer, and no single answer. Evolutionary biological drive to acquire calories. Psychological dependency on food. Inability to differentiate satisfaction from "being stuffed", likely due to environmental factors like negative education as a child or poverty mindset in parents. The perceived difficulty of altering diets for longevity. Self-hate. I'm sure there are scores more reasons for this, and no single concept or mindset is large enough to fully accurately embody the breadth of reasons why people remain obese in a world that actively disincentivizes obesity in every measure of life satisfaction. People outside of that fail to empathize with the plight of obese people. They blame them for living a life that is generally unintentionally thrust upon them. They do not see obesity as a disease but as a choice and then mock or dismiss them for being obese, even though by all metrics it is a disease. People tell obese people to diet like they tell alcoholics to quit drinking or drug addicts to quit using drugs and honestly believe their words have contributed value to humanity, but unlike drug addicts or alcohol, there is no cold turkey for obesity other than death. People must eat. That includes obese people. If you can figure out a way for a crackhead to smoke crack 3 times a day until they feel satisfied with how much crack they have smoked without remaining a crackhead, then you might be able to figure out how to get an obese person to eat 3 meals a day until they feel satisfied without remaining obese.
neogodless 11mo ago
> not only regained significant amounts of the weight they had lost on the drug, but they also saw their cardiovascular and metabolic improvements slip away. Their blood pressure went back up, as did their cholesterol, hemoglobin A1c (used to assess glucose control levels), and fasting insulin. This does sound like "reversion to the mean", but saying it's "regaining weight" may be missing the bigger picture. More like "losing all previously gained health benefits." It's less clear how "unsafe" those regressions in health markers are.
apple4ever 11mo ago
Plus if you look at the numbers (found in the comments of that story): 17.5% maintained 75+% of their weight loss. 25% maintained 50-75% of their weight loss. 23% maintained 25-50% of their weight loss. 24% maintained 0-25% of their weight loss. I mean that's pretty good!
- apple4ever 11mo ago
  (Formatted better) * 17.5% maintained 75+% of their weight loss * 25% maintained 50-75% of their weight loss * 23% maintained 25-50% of their weight loss * 24% maintained 0-25% of their weight loss.
mgarfias 11mo ago
Well, I didn’t produce enough T on my own anyway, so what the hell.

by tyleo 11mo ago

gtirloni 11mo ago

If you're on TRT, you are already not producing enough on your own.

tortilla 11mo ago
Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol* * not me but I see it with men in my age range
- PartiallyTyped 11mo ago
  I am a big fan of Dr Rohin Francis, and this landed on my youtube's front-page recently https://www.youtube.com/watch?v=FPsKTfFQFqc https://www.youtube.com/watch?v=FPsKTfFQFqc
- Aurornis 11mo ago
  I’m getting downvoted in another comment for saying this, but it’s a growing problem. In some surveys of TRT patients up to 1/4 of them didn’t even have their testosterone levels measured before being prescribed TRT. The men’s health clinics are finding excuses to diagnose everyone who calls. The lifetime value of a monthly TRT customer is very high.
- chimeracoder 11mo ago
  > Unless you went on when you weren't really low because the men's vitality clinic pushed you into a treatment protocol Saying that the men's vitality clinic "pushed you" into a treatment protocol is like saying that a fertility clinic pushed you into getting pregnant. Sure, it's a common outcome, but you had an idea of what you wanted out of it before you walked in the door.
  - dragonwriter 11mo ago
    > Saying that the men's vitality clinic "pushed you" into a treatment protocol is like saying that a fertility clinic pushed you into getting pregnant. No, it isn't. “Men’s vitality” doesn’t mean “getting pumped with testosterone regardless of indications” the way “fertility” means “getting pregnant” in either literal denotation of words or the understanding of the general population. > Sure, it's a common outcome, but you had an idea of what you wanted out of it before you walked in the door. Yes, but in the case of fertility clinics, getting pregnant aas definitely the outcome beinf sought. Being pumped with testosterone isn’t the outcome being sought from a men’s vitality clinic, it is (even for the people who are actively thinking about it) a mechanism (and not an appropriate one for every patient) for atteempting to acheive the desired outcome. If you go to a fertility clinic and they don't attempt to identify the source of your fertility issues and just pump you with hormones not indicated for your specific issue, that would be wrong, too.
    - chimeracoder 11mo ago
      > No, it isn't. “Men’s vitality” doesn’t mean “getting pumped with testosterone regardless of indications” When I Google "men's vitality clinic", the top result I see is titled "Your experts for testosterone replacement therapy...". TRT is front and center. > Being pumped with testosterone isn’t the outcome being sought from a men’s vitality clinic, it is (even for the people who are actively thinking about it) a mechanism (and not an appropriate one for every patient) for atteempting to acheive the desired outcome. This is such a weird distinction to try and make. I frequently see ads for these services, and even when they're not so explicit as that one is about what they're selling, it's extremely clear what demographic they're going after and what the hook is. Testosterone being a Schedule III substance, "men's vitality" is the way that they can legally advertise an service that prescribes AAS. It's no more of a secret that men's vitality clinics prescribe testosterone than it is that fertility clinics are prescribing estradiol. Both of these are sex hormones that induce a specific effect on the body which the patient is looking for. Can I imagine someone walking into a men's vitality clinic and being surprised that they're getting offered testosterone? Sure, and there's also that German couple who went to a fertility clinic because they weren't having a baby, and were surprised to learn that they needed to start having sex. Clueless people exist. That doesn't mean that it's not readily obvious to anyone who's paying attention what these clinics exist to do, and how they do it.
Aurornis 11mo ago
Unfortunately that’s not true any more. TRT over prescribing is a major problem right now. Studies of TRT patients have even shown that 1/4 of TRT patients may not have had their testosterone levels measured before being prescribed TRT: (Source https://pmc.ncbi.nlm.nih.gov/articles/PMC6406807/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6406807/ ) Completely unacceptable given how cheap testosterone testing is, but its happening. TRT clinics have also become a big business. Their business model relies on prescribing TRT to anyone and then charging them monthly or quarterly to continue receiving those prescriptions, which as the parent comment noted become physically necessary after TRT causes the testes to atrophy. The trick the clinics are using now is “diagnosing by symptoms”. They have a long list of “symptoms of low T” and the patient is basically prompted to check off enough boxes to justify TRT. It’s the same model as the medical marijuana card businesses where you can go in and the doctor will “find” a reason to give you the prescription. It’s a real problem when combined with social media influencers who tell people that everything is a symptom of low testosterone and TRT will fix it.
- gadders 11mo ago
  >>The trick the clinics are using now is “diagnosing by symptoms”. You can't really diagnose by levels, though, unless you knew what that person's previous levels were. Setting an average across a population is not really realistic - you can't say Shaq should work to the same levels as, say, Emo Phillips. TRT is normally used due to aging, though, so you are unlikely to have your testosterone levels spontaneously recover as you get older. You do tend to need to be on it for life, in the same way that women stay on HRT. However, if you did need to get off, bodybuilders have "post cycle therapies" to kick start production so it seems to be possible.
  - Aurornis 11mo ago
    If someone shows up with a testosterone level of 700 you can (and should) explain that low testosterone is not the explanation for whatever they’re suffering from. The TRT clinics are ignoring levels or even not testing at all. They’ll find an excuse to prescribe to someone even who has clinically high levels because they want the monthly recurring revenue from keeping that customer for life.
theptip 11mo ago
But TRT suppresses endogenous production further, so if you go off it you’re worse than when you started.
asafira 11mo ago
Isn't there TRT that doesn't impact your endogenous production? (HCG, SERMs)

mise_en_place 11mo ago

By what mechanism? That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The question is, why would someone with clinical hypogonadism cease TRT?

Aurornis 11mo ago
> That's not how it works. LH and FSH are suppressed when you're on TRT, but they stabilize after cessation. The testes atrophy over time when LH and FSH are suppressed. Even if LH and FSH return (which isn’t guaranteed) the testes need to be able to respond to those hormonal signals, but atrophied testes do not respond the same. For someone with true intractable hypogonadism this hardly matters because they weren’t capable anyway. Many people prescribed TRT today don’t actually have intractable hypogonadism, though. Body builders have some tricks to try to reverse this, but it’s not perfectly effective and even body builders know to cycle their steroids to avoid having prolonged periods of suppressed HPG axis activity. I was involved with weightlifting in my younger years but never dabbled with steroids or TRT. Everyone I know who did try testosterone or steroids thought they were doing it the safe way (HCG, PCT, limited cycle length) but became unable to produce enough endogenous testosterone by their 40s even with SERMs. Men on TRT for years will have considerable testicular atrophy that is not totally reversible. > The question is, why would someone with clinical hypogonadism cease TRT? TRT is no longer limited to men with clinical hypogonadism. Men’s health clinics that advertise on social media, TV, and radio will prescribe to anyone who contacts them (and pays cash for the prescription and gear). In some surveys of patients on TRT, 1/4 of patients didn’t even have testosterone levels measured prior to initiation of TRT.
- mise_en_place 11mo ago
  > TRT is no longer limited to men with clinical hypogonadism. Men’s health clinics that advertise on social media, TV, and radio will prescribe to anyone who contacts them (and pays cash for the prescription and gear). In some surveys of patients on TRT, 1/4 of patients didn’t even have testosterone levels measured prior to initiation of TRT. That's hugely problematic if true. They should be investigated and if found of wrongdoing, have their medical licenses revoked.

sReinwald 11mo ago

Strange framing, isn't it? Bariatric surgery shows 25-65% significant regain rates depending on definition and timeframe. And regular dieting is even worse. Nobody would frame that as a safety issue. That's... just how weight loss works, not a unique GLP-1 problem. Calling a return of symptoms (obesity) a "safety issue" is like saying insulin has "no safe off-ramp" because diabetics get hyperglycemic when they stop taking it. Fear gets clicks, I guess.

csense 11mo ago
At some point, somebody at the site changed the title. The old title was "GLP-1 Drugs Improve Heart Health, But Only If You Keep Taking Them." How do I know that? The URL slug tells the tale. > Fear gets clicks, I guess I strongly suspect this is the reason the title was changed.
- Thegn 11mo ago
  I know they (Ars Technica) do A/B title tests sometimes from discussion with one of the people who works there.
- cauliflower2718 11mo ago
  The original title is so much more informative. It might be so informative that many people didn't feel a need to read the article.
bsder 11mo ago
It's also very strange because more than 75% had some level of sustained weight loss after several years. That's way better than any other weight loss program. Nothing else even comes close.
m463 11mo ago
well, it could also be from a "do no harm" standpoint. (although looking into it, it seems many oaths never actually say "first do no harm")

taeric 11mo ago

Yeah, I would fully support "easy" there, but regaining weight isn't something most people think of as danger.

fwip 11mo ago
Many people who are losing weight are doing so because they're concerned about their health, right? Especially heart health.
- taeric 11mo ago
  I mean, sure? But this is like saying there is no safe way to get old. Which, is kind of accurate. But not what people think of when you say safe.

financltravsty 11mo ago

As an experienced polysubstance researcher, that's not exactly accurate. TRT cessation does not inherently cause men to have suppressed hormone levels after. With precautions and extra steps like HCG to maintain leydig cell/testicular function, preventing atrophy, one may safeguard against that risk. Coming off TRT, yes you will have lower levels as your HPTA has been suppressed by exogenous hormones. One may speed up this recovery using "PCT" (post cycle therapy), which involves taking a SERM (selective estrogen receptor modulator, e.g. enclomiphene) to resensitize and restart your HPTA. However this is not always necessary, and if one takes a look at the HARLEM study, most users return to their baseline levels within a year of going cold turkey. In the cases of true permanently lowered levels of hormones, I believe the two most common reasons are: using other AAS besides testosterone (1) and lifestyle or health factors that correlate with the need to be on TRT (2). With 1, this can be seen in users of decadurabolin (deca), which notoriously has hormone receptor active metabolites that last around for atleast a year, continuously suppressing the system. Or trenbolone (tren/cattle bulking hormone) which is inherently neurally and endocrinically otherwise toxic. With 2, you hop on TRT because there is some reason your hormones are not at healthy levels. Whatever the reason is, it is still there, and once you've stopped bandaiding the issue its effects resurface. --- I have also used many GLP-1s (semaglutide, tirzepatide, and retatrutide). No there is no off-ramp, but the only effects I've noticed are a return to my baseline of appetite, and neurological state. N.B. GLP-1s are good for impulse and behavioral disorders like ADHD, which it did help. However, I have decided to not take it due to the negative effects on personality and reward seeking behavior. They are neuro-active in the brain, and their effects I've decided are not worth it.

tyleo 11mo ago
This reasoning is not flowing through for me. It feels like you are saying: 1. There is an off ramp for TRTs but some people have, “true permanently lowered levels of hormones.” 2. For GLP-1s, “there is no off-ramp, but the only effects I’ve noticed are a return to my baseline.” To clarify my original post, I consider the ability to return to baseline to mean there is an off-ramp and permanently impacted to mean there is no off-ramp.
- 11mo ago

observationist 11mo ago

"Those poor people have no agency and their behaviors are outside their control!" Well, I guess we have no choice but to affirm and reinforce their lack of agency and ensure we put them on drugs for the rest of their lives! It's ironic that one of the effects of this drug seems to be reducing the impact of impulsive behaviors, reducing cravings from other drugs and alcohol and cigarette addictions. The hat trick for someone might be to get on one of these GLP-1 regimens, wean themselves out of whatever crisis/crises they are in, end their GLP-1 regimen with a heroic mushroom trip, and physically move to a new environment, where they don't have any of the default triggers or patterns to fall back on, and everything is fresh and can be built up from scratch. I think the medicalization of human agency is one of the great evils of our time. The implication and impact of doctors, bureaucrats, and bean counters making sweeping policy, regulation, and legal decisions on behalf of the peasants and peons who just don't know better. The casual dismissal of fundamental basic principles is outrageous, especially in service to the politics and idiotic tribalism.

acuozzo 11mo ago
> "Those poor people have no agency and their behaviors are outside their control!" Our complex modern society has a daily buy-in. Some people were born and/or raised for it and the cost for them is nothing. Others need to soothe the pain of shoehorning themselves into it by chain-smoking while working a jackhammer or shoveling cereal into their face while programming. Yes, these behaviors are technically within their control, but are you really going to suggest that we can solve the underlying problem(s)?
BizarroLand 11mo ago
I think your opinion is valid from your point of view but missing an important part of the bigger picture. Obese people typically do not try to become obese. Most obese people have tried to lose weight and find that they lack the tools and skills needed to succeed, and many of the ones that do succeed only do so temporarily. Why is that? It's a question with no simple answer, and no single answer. Evolutionary biological drive to acquire calories. Psychological dependency on food. Inability to differentiate satisfaction from "being stuffed", likely due to environmental factors like negative education as a child or poverty mindset in parents. The perceived difficulty of altering diets for longevity. Self-hate. I'm sure there are scores more reasons for this, and no single concept or mindset is large enough to fully accurately embody the breadth of reasons why people remain obese in a world that actively disincentivizes obesity in every measure of life satisfaction. People outside of that fail to empathize with the plight of obese people. They blame them for living a life that is generally unintentionally thrust upon them. They do not see obesity as a disease but as a choice and then mock or dismiss them for being obese, even though by all metrics it is a disease. People tell obese people to diet like they tell alcoholics to quit drinking or drug addicts to quit using drugs and honestly believe their words have contributed value to humanity, but unlike drug addicts or alcohol, there is no cold turkey for obesity other than death. People must eat. That includes obese people. If you can figure out a way for a crackhead to smoke crack 3 times a day until they feel satisfied with how much crack they have smoked without remaining a crackhead, then you might be able to figure out how to get an obese person to eat 3 meals a day until they feel satisfied without remaining obese.

neogodless 11mo ago

> not only regained significant amounts of the weight they had lost on the drug, but they also saw their cardiovascular and metabolic improvements slip away. Their blood pressure went back up, as did their cholesterol, hemoglobin A1c (used to assess glucose control levels), and fasting insulin. This does sound like "reversion to the mean", but saying it's "regaining weight" may be missing the bigger picture. More like "losing all previously gained health benefits." It's less clear how "unsafe" those regressions in health markers are.

apple4ever 11mo ago

Plus if you look at the numbers (found in the comments of that story): 17.5% maintained 75+% of their weight loss. 25% maintained 50-75% of their weight loss. 23% maintained 25-50% of their weight loss. 24% maintained 0-25% of their weight loss. I mean that's pretty good!

apple4ever 11mo ago
(Formatted better) * 17.5% maintained 75+% of their weight loss * 25% maintained 50-75% of their weight loss * 23% maintained 25-50% of their weight loss * 24% maintained 0-25% of their weight loss.

mgarfias 11mo ago

Well, I didn’t produce enough T on my own anyway, so what the hell.