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.
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.
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.
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.
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?
That's hugely problematic if true. They should be investigated and if found of wrongdoing, have their medical licenses revoked.
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 prescribing rules allowed telehealth providers to give schedule II prescriptions to new patients remotely, so services were created to advertise on TikTok and give prescriptions for a monthly fee. The FDA cracked down on these, though.
There’s even a famous story of a whistleblower who worked at one of these clinics and got reprimanded for not prescribing Adderall enough. There was a leaked memo where they pushed providers to prescribe Adderall over other options because their data showed the highest customer retention rate that way.
I don’t think it’s analogous at all to medical marijuana.
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.
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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.
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 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.
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.
* not me but I see it with men in my age range
The struggle doesn't stop when you stop losing. My personal experience was that it takes about 2 years for the new 'normal' to kick in. (I lost 60lbs when I was in my early 20s and kept it off until today. The 'after' period was as taxing as the 'losing' period, but in a different way)
At that point only can you 'relax' a bit around your body's cravings for calories.
This has already been studied extensively:
https://pmc.ncbi.nlm.nih.gov/articles/PMC5764193/
It's not the worst thing in the world to be on a medication for a couple years rather than a few months, but long-term study of this class of drugs is certainly warranted and necessary.
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 understand why we have an obesity epidemic and eventually finance changes to combat it? Ideally the drug makers would do this without requiring government intervention, but I doubt they will.
So weight loss was actually maintained for most people -- the hard part is finding a healthy daily lifestyle which can maintain the drastic effects of GLP1s.
This information isn't new -- weight regain has been studied before and I've written about it before:
https://glp1.guide/content/do-people-regain-all-the-weight-l...
The missing piece to this article is just how bad the alternative is -- never having the cardiovascular and metabolic benefits is clearly not the best strategy (and if simply changing patterns was so easy, people would have done it already).
GLP1s don't work for everyone but they're pretty close to miraculous in effect given the balance of positive and negative side effects. Making GLP1s cheaper & more tolerable then figuring out how to actually deal with the complex web of how to keep the weight off sustainably for most people seems like the right way forward here, not avoiding potentially life-saving medication because you may not be able to get off of it as fast as you want (if you can afford it).
BTW, there is already generic Liraglutide, and legal workarounds for getting compounded Semaglutide that already mean no one pays the $1000 that was in the zeitgeist a while ago. Even Lilly Direct and similar outfits from Novo sell for $500/month, with the $150/month pricing coming soon[0].
[0]: https://glp1guide.substack.com/p/negotiations-are-underway-f...
So there appears to be an off-ramp, we just don't know what it is.
calories_in < calories_out seems to be a pretty good formula.
These symptoms will be familiar for anyone who has lost weight dieting and then returned to eating junk food.
You don't say ;-) I lost 50 lbs and have kept it off for the past year while maintaining great BP. But I'm under no illusions GLP-1 medications don't have dangers and cause problems for many. It should be handled on an individual basis like any serious medication.
That said, is someone losing a lot of weight then gaining half of it back worse than them just staying where they were? I don't know the answer to that one.
The trick, of course, is to repeat the process as you asymptotically approach your goal.
Zeno's paradox of mass.
My wife is back devouring cookies after being on mounjaro for 4 months. Thankfully she lost most weight all by herself so wasn’t totally reliant on the medication. But it’s crazy how noticeable the difference of one’s eating habits when on and off it.
Then, I stopped working out, and gained 15lbs. Exercise: no safe off-ramp for some.
>stop taking weight loss drug
>regain weight
>there is no safe off-ramp for GLP-1
I guess taking weight loss drugs don't really teach healthy eating habits.
I think that it is quite unsurprising that without the drug a large amount of people revert to their previous behavior and with that will revert to their previous weight.
I think the intuition many people have--which I am not at all defending as correct, but it certainly isn't so obviously wrong that we should scoff at someone for thinking it works this way--is more like "if my weight was stable before I did this intervention, I just need to lose the weight and then my weight will once again be stable after it"; in this mental model, one would assume you only need lots of willpower to lose weight: after, you only will need as much willpower as you already know you have to not gain it back, as it isn't as if you are gaining weight currently.
That's literally the implication of these findings.
But one can always hope for a miracle drug that you can take for a bit, then stop, and have its effects last. Now we know that Ozempic is not that drug.
There's of course a risk that when they stop the drugs that hunger will drive them to re-establish those habits, but now that they have new habits that fight that hunger they are in a much better position to resist it than they were when they'd initially established their eating patterns.