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There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

arstechnica.com

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Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#41

Post by perelin »

aishsh wrote: post #35
perelin wrote: post #22

As a GLP-1 user im really surprised that this is newsworthy. The mechanism of how these drugs lead to weight loss is appetite reduction. On GLP-1s -> less appetite, off GLPS-1s -> more appetite. Given the general health benefits that are being observed with GLP1-s the only reason to get off them is costs imo. They are absurdly expensive. Hope this will change in the next 10 years with patents running out and generics…

> Given the general health benefits that are being observed with GLP1-s the only reason to get off them is costs imo There’s also the perverse incentives wrt broader society. Enabling the average person to control their physical health is orders of magnitude better for society and orders of magnitude less profitable than the current trends. Maybe a setup where glp drugs are nationalized and only used to further under…

100% agree. But that also feels like the elephant in the room somehow. Most western pension systems are stretched to (or beyond) their limits already. I expect that having GLP1-s widely available will extend the life of a LOT of people even further. And then ... what? Im really surprised that nobody talks about that.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#42

Post by financltravsty »

tyleo wrote: post #4

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 testoste…

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.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#43

Post by Aurornis »

SpicyLemonZest wrote: post #38
mise_en_place wrote: post #34

Earlier quoted context omitted.

> 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…

I dunno. It seems straightforwardly analogous to the fake medical marijuana clinics you see in places where recreational use isn't legal, or the countless online pharmacies with doctors on retainer to prescribe Ozempic and Viagra. It's not how I would design the medical system if I were in charge, but these aren't addictive substances like opioids.

Testosterone induces physical dependency which can be irreversible when taken for prolonged periods.

I don’t think it’s analogous at all to medical marijuana.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#44

Post by gadders »

Aurornis wrote: post #21
gtirloni wrote: post #12

Earlier quoted context omitted.

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

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/ ) Completely unacceptable given how cheap testosterone testing is, but its happening. TRT clinics have also become a big busi…

>>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.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#45

Post by jstummbillig »

Aurornis wrote: post #40
mise_en_place wrote: post #34

Earlier quoted context omitted.

> 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…

It’s true. You can even go on Reddit and find anecdotes and guides about which clinics to call and what to say to get prescribed with minimal hassle. Some of the clinics were even prescribing anabolic steroids intended for terminal cancer patients. If you want to read about something even crazier, look up the services that were started during COVID to be prescription mills for Adderall or Xanax. The relaxed COVID pre…

Did you use a LLM to write these comments?

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#46

Post by financltravsty »

Aurornis wrote: post #31
mise_en_place wrote: post #28

Earlier quoted context omitted.

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?

> 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…

Curious on your thought to my reply: https://news.ycombinator.com/item?id=46059074

Can you share your longitudinal anecdata? I am considering going back on AAS for the QoL benefits, but would like to create a better mental model of long-term ramifications for testicular health.

It's my understanding that 40, it simply is expected that your hormones levels will be much lower (and that is not necessarily a bad thing). However my mind is failing to grasp what long-term damage TRT can do to the HPTA when not using an obscene amount of gear and on HCG.

Trying to figure out the mechanism. Perhaps receptor desensitization and epigenetic compensatory changes?

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#47

Post by observationist »

tyleo wrote: post #4

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 testoste…

"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.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#48

Post by Aurornis »

jstummbillig wrote: post #45
Aurornis wrote: post #40

Earlier quoted context omitted.

It’s true. You can even go on Reddit and find anecdotes and guides about which clinics to call and what to say to get prescribed with minimal hassle. Some of the clinics were even prescribing anabolic steroids intended for terminal cancer patients. If you want to read about something even crazier, look up the services that were started during COVID to be prescription mills for Adderall or Xanax. The relaxed COVID pre…

Did you use a LLM to write these comments?

I do not. I’m typing on my phone from a waiting room. I’d probably have fewer incorrect words and awkward sentences if I did.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#49

Post by jtrn »

Same is true for: insulin, Levothyroxine, Antiretroviral Therapy (HIV), Enzyme Replacement Therapy ( Pompe Disease or Gaucher Disease, antipsychotic medications for severe schizophrenia. And many others. And here’s the interesting twist, the closer the Number Needed to treat is to 1, the more helpful the medication should be viewed. All these medications have an extremely low NNT, including GLP1s.

Re: There may not be a safe off-ramp for some taking GLP-1 drugs, study suggests

#50

Post by chimeracoder »

tortilla wrote: post #13
gtirloni wrote: post #12

Earlier quoted context omitted.

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

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

> 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.

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