PragmaticPulp

> It’s not much fun.

TRT forums are kind of fascinating because they're full of people who though (or, sadly, were convinced by TRT clinics) that TRT was going to be amazing, solve all of their problems, and make them feel like 20 year olds again.

Then the realities of getting your hormones from imperfect exogenous sources and dealing with all of the imperfect complications thereof set in. A lot of disappointed stories from people who feel marginally better but thought it was going to cure every struggle in their lives. Unfortunately, a lot of people with depression issues also end up in TRT clinics because hypogonadism is a more palatable diagnosis than mental health issues for many.

> You can just dose on HCG for a month and your natural levels will come back.

That is the broscience consensus, but it's not as bulletproof as people like to believe. It will probably work for a 25 year old after 1-2 months of dabbling, but the TRT forums are full of stories where these tricks don’t work or stop working after extended use.

The tricks are not guaranteed like some of the forums or sketchy TRT clinics will claim. Atrophy can be permanent after relatively moderate periods, even with all of the HCG and SERM tricks.

> You're right though to point out that the body loves homeostasis and will downregulate endogenous testosterone production if serum levels are high from supplementation.

Any supplementation will, by definition, raise serum levels higher than they were before the extra testosterone was added.

This is what causes the downregulation, so of course it will happen. Like I said, people like to be in denial about this because it doesn’t necessarily happen right away, but it happens.

> True, but not all of the permanent effects are negative.

That’s a weird way of looking at it. Those extra muscle nuclei won’t be of much use if you discontinue TRT and your endogenous system is too atrophied to keep up with basic bodily needs. You have to look at the big picture.

Your comment is a good example of the denial I was talking about: For whatever reason, some people don’t want to believe that the negative effects will happen to them, and they want to ignore the consequences or change the subject to only talk about the positives.

TRT is tricky because patients will feel an initial boost in their early treatment. They assume this feeling is their new normal, but then things level out and they go back to a more normal-ish feeling.

Severe testosterone deficiencies respond very well to treatment. Going from 55 year old to 25 year old levels isn’t as dramatic.

TRT forums are full of people with normal or low-normal who thought TRT was going to solve all of their problems and make them feel young again, only to be disappointed that they don’t really feel much of anything after a while. However, now they’re stuck on it for life because their endogenous production has dropped off.

Using exogenous testosterone will shut down your endogenous production, or at least permanently reduce it. A lot of people will try to tell you it can be avoided with the right combination of SERMs and HCG, but there are a lot of people who thought they were doing the exact “right” protocols who end up on TRT because their testicles were permanently atrophied. It’s one of those topics where everybody thinks they’re the exception who will avoid the consequences, but do it long enough and it will happen.

There are also a lot of secondary effects that people underestimate. For example, the extra testosterone (beyond normal levels) will result in excess estrogen, which can grow excess breast tissue in males. There are medications that can interrupt this process, but getting the dosage right is difficult and many people fluctuate around ideal values. Fluctuation and low estrogen values will cause significant mental health effects. Again, these are theoretical avoidable under perfect conditions yet almost everyone ends up with some of it eventually. I had a friend who tried using testosterone all the “right” ways with excessive lab tests, HCG, cycling, SERMs, AIs, and everything else. It still ended up destabilizing his mental health and making him prone to anger and bouts of sadness/crying. He denied it for a long time because he thought it couldn’t possibly be his by-the-book protocol, but eventually we got him to admit it was a problem. Denial runs deep.

Basically: Don’t go down this path unless you accept that it’s going to have significant downsides and consequences, many of which are long lasting or permanent. And definitely don’t dabble in taking testosterone or steroids as an early step in a weightlifting career or as a trial to see if it gives you a boost. The consequences can/will be permanent for the rest of your life.

> I’m getting more convinced that the best move to improve the likelihood of a successful IPO (which IMHO this whole API clusterfuck is all about) is to fire spez and install a sane CEO.

Spez’s PR moves aren’t great, but it’s unrealistic to expect a new CEO to go easier on API costs.

If anything, a new CEO would make more of a push toward monetization. Reddit has been very light handed about monetization, charging, and tolerating ad blocking. Bring in a new CEO, chosen by the board, and it would likely be a full on squeeze toward making money even if it costs them a vocal minority of users.

> They are valuable only to Reddit for their potential to be monetized.

Why are you dismissing this? I don’t understand all of these comments talking about Reddit as if it was 100% free to operate and the only important users are the commenters

> It was met with unanimous wtf is wrong with you, go outside.

“Go outside” is an ironic comment, given that the subreddit blackout doesn’t appear to be all that popular among casual Reddit users. It’s popular among the chronically online people who use Reddit so much that they’re intimately involved in every detail of the site, but 98-99% of users don’t use 3rd party clients.

> I get the feeling spez is creating new accounts and posting as them again.

It’s getting weird that Redditors are turning into conspiracy theorists, believing that anyone who disagrees with the popular narrative must be a shill, a plant, or the CEO himself speaking to them.

No, the CEO of Reddit isn’t spending all day coming to your niche subreddit, creating new accounts, and sockpuppeting opinions to the handful of people there.

> The software engineer is one example of a high paying bullshit jobs.

Of course, because software has never been useful to anyone.

> Also important to note that this is an indicator that Reddit has lost all trust from (this part of) the community.

Assuming the worst, ignoring details that violate the narrative, and circulating ragebait without verification are all staples of mainstream Reddit content.

It’s not surprising that the Reddit outrage/grievance machine has turned on itself and is now assuming the worst and getting outraged at every turn.

This is basically spamming, but with a time delay so the moderators won’t see it.

Worse, the data is already archived by the data collection services. The people who suffer are going to be average users trying to find some answer to a question by searching Reddit, only to discover jumbled messes of words that don’t make sense.

Or HR/hiring managers spend a few minutes on LinkedIn looking for employees who have 1st or 2nd order connections to the candidate. If someone has been working in an industry for 5-10 years it's not hard to find someone who knows someone who worked with them.

People change companies every few years. If a company has 100 engineers and half of them get new jobs after 3 years, you could now have people with 2nd-order connections at 20-50 different companies.

Repeat for several cycles and it becomes very easy to find someone who knows someone who worked with a candidate. LinkedIn makes this extremely easy.

Of the tips in this article, I think this one is simultaneously the most well-known and the most underrated:

> Getting a job gets you a professional network, which you can try to turn into a friend network.

Getting a job isn't enough to start building a network. You have to do well at that job, be a good person to work with, and step out of your comfort zone to meet new people.

I've seen a growing number of people learn the hard way that your behavior in the final months of a job leaves a lasting impression. One of the most motivated engineer ladder-climbers I know was very good at interviewing and getting new jobs, but he developed a habit of burning bridges on the way out: After about a year at the company he'd gradually diminish his work output and spend 80% of his day searching for new jobs, interviewing, and negotiating bigger raises at his next job hob. This worked for a while, but after 4 or 5 rounds he had built a reputation for slacking off for a few months and then leaving companies. Word traveled, and he discovered that new jobs would only hire him with longer vesting schedules and sign-on bonuses that had to be paid back if he left before 2-3 years. Eventually nobody well-connected wanted to hire him because they had heard so many stories about him underperforming and bailing at the 1-year mark, despite interviewing well and performing great in the first few months. He finally moved out of state to start over in a new network.

What I'm saying is: The strongest networking you do might not feel like networking. It's years of accumulated reputation. Word travels and people check references. Reference checking felt like it was paused for a few years when everyone was hiring as fast as possible, but now I'm getting reference check calls/texts/DMs more than ever before.

I've had mixed results with networking-focused activities. I've met some good people at networking events, but you have to actively filter out the loud professional networkers and seek out the other people like yourself. The best contacts are not always the loudest, most outgoing, most extroverted people at these events. In fact, some of those people are sharks who are only interested in networking as far as they can use you for leverage, clout, or your connections. Tread lightly.

> Any substances widely consumed by people should be regulated and tested before they are sold to the public

Even after marijuana legalization, many states still have thriving underground marijuana markets.

Many people who consume a lot of a substance over time will inevitably seek out cheaper sources. The sources complying with regulation and testing requirements, however light, will be more expensive than someone growing some plants in the back of a spare building somewhere.

The problem is exacerbated for more expensive and addictive drugs. The few people I’ve known who became addicted to opioids were spending significant amounts of money to maintain their habit and traveling to increasing dangerous situations to get better prices.

It’s optimistic to declare that everyone should have access to well tested drugs, but the reality is that it’s not a magic bullet. I also have some serious doubts about the narrative that increasing availability of drugs won’t contribute to more widespread addiction problems.

Reddit has built a reputation for being "not social media", but in my opinion it has come to embody most of what people say they hate about social media. If I visit Reddit without logging in, the content on the home page is disastrously bad: Videos of fights with comments from people cheering on the violence. Screenshots of exaggerated Tweets taken out of context. 10 different stories about the latest tragedy somewhere in the world and editorialization about how it's a sign the world is coming to an end. Ragebait videos taken from TikTok and other social medias for the express purpose of getting Redditors riled up and angry.

I know the story goes that you can avoid it by carefully selecting the right subreddits, but in my experience the trash content bleeds into everything. Even the technical subreddits I followed have become inundated with low-effort posts and people who just want to pick fights.

> I don't think they're losing anything of value when I stop browsing. I've been using old. for years, and always been pretty strict about blocking ads.

Thanks for being honest about it. I suspect Reddit is well aware that the average user (who views ads) is not likely to be among the angrier power users who are pulling the strings. If anything, I'm starting to get a sense that the non-commenters and casual users are getting sick of the mods using their power to shut the conversation down. The average user doesn't use Apollo and doesn't care about this drama. I think it's easy to forget this when the vocal minority of power users are upvoting angry topics and mods are shutting down subreddits.

> You could run a company that sustains itself and its employees, maybe makes a modest profit.

Reddit is not profitable, though.

They're burning through investment cash just to keep the lights on. That can't last forever, so they have to do something.

> So it was always about money.

I'm more surprised that anyone thought it wasn't about money.

Reddit is a business. An unprofitable business. They have to do something to turn a profit eventually.

> I like HackerNews because the conversations are mostly intelligent and polite

Comment sections like this one highlight the risks of mistaking comments that look intelligent and polite for authority. The number of confident, polite posts in this comment section that are giving out factually incorrect information is incredible. Someone down below was speculating about this drug’s cardiotoxicity in ways that could be dismissed within 15 seconds of reading the Wikipedia page, but they presented their speculation as if it had an air of scientific authority.

The number of commenters trying to suggest that psychedelics, which do not interact with the 5-HT4 receptor studied in this article, are a substitute for this drug or otherwise should be used for this indication is astounding.

> I wish we stopped treating serotonin as a button that automatically improves mood.

We don’t. Studies like this are specifically searching for mechanisms by which serotonin and mood are related.

I think you’re projecting the pop-culture idea of serotonin on to the research.

No, Prucalopride was specifically studied for cardiac complications.

Why is there so much rampant misinformation in this comment section when the facts are a simple Google search away?

> I came to the comment section to mention other seratonergic drugs that do something similar to what the study mentions. Psilocin is a serotonin 2A agonist, LSD is a 1A agonist (according to a quick google search), and this new drug works on "4" receptors. All of which seem to have similar beneficial therapeutic effects when used properly.

Serotonin receptors are not interchangeable at all.

5-HT2A and 5-HT4 receptors have completely different effects and functions. You can’t suggest that drugs that work on one are similar to the other.

They are nothing alike.

For anyone coming to this comment section in hopes of understanding this further: This comment section is full of misinformation and discourse about drugs that are completely unrelated to what’s discussed in the article.

Serotonin isn’t a singular system in the brain. Psychedelics generally don’t interact with the receptor mentioned in this article (5-HT4) so all of the anecdotes talking about LSD or mushrooms do not apply to this story at all. Serotonin agonists are not interchangeable and have very different effects depending on their targets.

The drug in this study (Prucalopride) has been noted to influence depression symptoms positively for some time. However, it has also been noted to be associated with suicidal ideation in some vulnerable populations. This is an emergent area of research and absolutely should not be taken as a suggestion for self-treatment.

If that’s not enough to convince you to not self-experiment, you should know that Prucalopride is primarily used as a constipation treatment. If you take it, you’re going to have some dramatic bowel effects.

Please understand that these articles are interesting, but HN comments about anything related to psychedelics, serotonin, or dopamine are often quite far from the mark (despite being very confident in their delivery).

> Psychedelics and other serotenergic drugs are becoming the defacto treatment method for a whole host of ailments.

They are definitely not. Anecdotes aside, psychedelics are extremely overhyped right now and the downsides are heavily downplayed online. The studies about psychedelics and depression use heavy amounts of therapy and careful professional guidance, which the at-home experimenters don’t get.

Psychedelics can also produce intense negative reactions, such as persistent false beliefs or even a worsening of anxiety and depression that lasts for some time. Many people online rush to dismiss these negative anecdotes if their personal experience was different, but they’re much more common than enthusiastic internet commenters would suggest.

The health podcast industry is making this problem even worse. Many people consume content like Huberman’s podcast and assume he’s an expert because he speaks so confidently and at such lengths. Yet Huberman’s podcasts are well known to contain a lot of errors on very basic concepts and extreme exaggerations. He appears to well-versed in topics related to his domain of study, albeit with exaggerations of his findings to appease a podcast audience.

Once he steps outside of his domain and starts talking about dopamine this and dopamine that, his podcast will make neuroscientists roll their eyes. Yet he speaks so confidently that his audience is convinced they, too, are now experts on all things neuroscience.

> I think all of the "science" of using drugs to treat mental issues is at the level of advancement comparable to medieval blacksmiths doing dentistry.

Discounting an entire field of science like this, based on a second-hand observations, is exactly the kind of hubris the parent comment was talking about: There’s something about psychiatry and neuroscience that makes a lot of people who are good at engineering/software think that they are qualified to also be experts on the field of psychiatry.

You’re right that psychiatry and medication is a lot of trial and error, but that’s the most efficient and accurate way to determine which medications work with a patient. In a hypothetical perfect world we’d have more tools to predict ahead of time and this is an active field of study. However, nothing comes close to the speed and efficiency of just trying medications based on what has worked for many other patients with similar conditions.

Note they practitioners aren’t just guessing and hoping for the best. They are using a large body of research, clinical experience, and shared knowledge of their peers.

> Perhaps the relevant thing is "household where at least one person makes >100K/yr" since the benefits are probably tied to the type of job.

I think you're reading too much into the OP's off-hand guesstimate. At every company I've worked for, the engineers earning $200K are on the same health insurance as the high school graduate in the warehouse earning $40K/year. The higher compensation makes it easier to clear the deductible/out of pocket maximum hurdles, obviously, but there wasn't a secret insurance plan that got unlocked at higher compensation.

> 2. Take a break every 45 minutes.

Breaks are good when you're having half-day or all-day meetings. For example, when someone has travelled to the office and you're meeting all day.

For regular meetings with your normal office mates, if they're so long that you need to insert breaks then they should probably have been separate meetings.

Having everyone leave the meeting and then slowly meander back in always takes longer than it should. That 5 minute break can turn into 10, 15, or even 20 minutes as you try to track down the last person who wandered off and then got pulled into something else.

Just make the meetings concise enough to handle without a break. If you have more material, schedule a separate meeting for it.

Also, don’t neglect the role of moderation.

I tried browsing, but the top post is a photo of Hitler with the title “A man who did nothing wrong” and several upvotes.

The reality is hard, but the expectation half of this balance is getting exaggerated:

> We could be working 15-hour weeks, enjoying our free time, and living like people of the future.

Keynes’ 15-hour workweek essay wasn’t meant to be a rigorous study of how the future was going to look, nor was it representative of a widespread belief. Yet to this day it’s a favorite of journalists looking to anchor economic expectations so far away from reality that no living conditions could sound good by comparison.

More practically, I still see a lot of exaggerated expectations in the juniors coming through my employer. Maybe I’m getting old, but it’s becoming frustrating to watch people get six-figure jobs right out college doing remote coding work from the comfort of their homes with ample mentoring, only to complain because Reddit and Blind led them to believe they’d be earning $300K at FAANG jobs while working 20 hours per week. I know that’s not the focus of this article, but I do think it’s representative of how the gap between expectation and reality is being stretched wider and wider as people fall deeper into the internet/social media reality distortion field.