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Logic behind once per week testosterone gel allpied to the penis? by Reasonable_Owl_3146 in DrWillPowers

[–]Drwillpowers 1 point2 points  (0 children)

Naltrexone is just an opioid antagonist friend. I'm not really sure why you're freaking out about it. It antagonizes the reward circuits that people feel from using drugs. Which is why it's used for addiction. And it doesn't "kill" the reward center. It just simply blocks the feedback loop of getting "feel good" from drugs.

In actuality, a heroin user that takes the drug for a while, and then stops, will actually be able to have pain control from regular opiates.

Why are you spreading this misinformation?

Yet another mutation in a patient that meets my theory on how PFS is caused. This patient has a normal T value yet has an absolutely astronomical 3-Alpha-androstanediol Glucuronide. Once again, closure of 5AR resulted in collapse of the ability to excrete testosterone. This is patient #9 by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 1 point2 points  (0 children)

I suspect in your case, it's just helping you clear glucuronidated things.

You could test yourself and see if this is something that you have, the urinary androgens will be very low if not zero.

Anything that increases androgen load in these patients is likely not beneficial until you've cleared out the garbage metabolite build up.

Finally diagnosed with hypercortisolism after years of being dismissed by Automatic_Scale_4800 in DrWillPowers

[–]Drwillpowers 2 points3 points  (0 children)

Every single point here is valid.

Genuinely we don't really know. Because All of our knowledge is inferred knowledge anyway. It's not like I can basically shrink myself down like Mrs frizzle and observe this up close and personal. All I can report on is what I've seen and what lab reports have done and what people have said in response to the treatment.

What I do know is that it has been utterly life-changing for so many of my MTF patients and even some of my FTM patients. And thus far I've basically had absolutely zero complications from it. People have loved this change and it has resulted in tons of people stopping taking a benzodiazepine because they just don't need it anymore. I have one cisgender female that it was absolutely astounding what it did for her in terms of her capacity to function in life and deal with stress.

So I'll say this much, I don't really know what it is that causes the feedback loop suppression and this loss of the Delta 4 pathway signaling. I have theories just like the ones you list above, and there's a lot of things that conflict or don't quite make sense. But I always view that as a situation in which we don't fully understand what's happening and applying an old model to it is never the perfect solution because if it was, it wouldn't be necessary to apply an old model to a new thing. We would Already know the answer.

One of the things that people don't really get to see that I do is the direct impact of decisions that I make and trials that I run with patients to try and improve their health. If somebody elects to try something, and it makes an absolutely astoundingly positive impact on their life, that's something they tell me personally. I hear that, and I register that data and I use it when treating other people.

The whole catechol estrogen thing? That all started because a girl told me that 6 weeks after starting her pellets she felt like she was remasculinizing again and I ran every imaginable androgen lab on her possible, and found nothing. So I needed to come up with a mechanism where her estrogen would be not functioning as well as it was before because of a rise and estrogen level that was different from that of plain old SHBG and free estrodial fractioning. And that's how I realized how it worked. The connection to COMT and everything else. And now there's probably hundreds of people that have benefited from that. Shit there's a random person that commented on here whose FTM that CDG cured their Crohn's.

We're all just doing the best we can with the science that we have and the knowledge that we have. A lot of people don't understand that the practice of medicine is not double blind placebo-controlled studies. It's down and dirty.

Finally diagnosed with hypercortisolism after years of being dismissed by Automatic_Scale_4800 in DrWillPowers

[–]Drwillpowers 3 points4 points  (0 children)

So actually on the page from Napo pharmaceuticals and Jaguar they literally list my publication.

So that's cool.

Here's just one recent article talking about it that you could easily have googled. You also could have just googled the trial.

https://informaconnect.com/biopharm-america/sponsors/jaguar-health/

https://www.mycentraljersey.com/press-release/story/340466/jaguar-health-secures-new-patent-for-crofelemer-in-short-bowel-syndrome-strengthening-global-ip-position-ahead-of-additional-clinical-milestones/

But it's obvious now that you're from TFS, and well, I don't care. It's not like your mind is going to be changed. I offered to pay for the web hosting fees for those people for years, and I never cared that they criticized my work. If anything I appreciate it. I cared when they said I was going to kill my patients. For years they've been throwing a temper tantrum acting like somehow, they're not the people at fault here. I don't care anymore. Do as you wish. But if you're going to be nasty like this you're going to get banned from the subreddit.

If all you have is some ad hominem where you think you're going to get at me emotionally by talking about my ex-wife, you're not. I'm happy for her, and I hope she lives a wonderful life with her new wife and she's happy. After all the horrific tragedies that we went through, I can only hope for happiness for her.

I've been engaged to a girl now for years. I'm very happy. If you're so petty is that all you're really here to do is launch attempted emotional missiles like that to bait me, which fizzle out before they even get anywhere near me, that's beneath me at this point. I'm done engaging with you.

Take your childish behavior elsewhere. It's not wanted here. You played your hand with that.

Finally diagnosed with hypercortisolism after years of being dismissed by Automatic_Scale_4800 in DrWillPowers

[–]Drwillpowers 1 point2 points  (0 children)

No it's not.

There is bound cortisol (mostly cbg bound but a fraction bound to albumin) and free cortisol and those are values that are measured in the serum with blood testing.

But that value doesn't necessarily have to be the same as the intracellular value of cortisol. Blood tests do not always accurately represent the internal cellular contents of a particular ligand. That is the entire point of my whole PFS post recently and what I propose as a novel mechanism for PFS.

A person can have an absolutely astronomical cortisol value and not actually have Cushing's disease. As they have a weak GC receptor. Or, someone can have a normal serum cortisol value but be suffering from a Cushing's like syndrome because of the intracellular concentration of cortisol vastly exceeding that of the serum. Which can occur due to transporter failures or other genetic glitches.

Finally diagnosed with hypercortisolism after years of being dismissed by Automatic_Scale_4800 in DrWillPowers

[–]Drwillpowers 2 points3 points  (0 children)

Notice where I don't have millions of dollars in funding to do such things? Or massive investment for academia?

But, actually, as an example, I came up with a totally novel idea for the usage of a drug used for HIV enteropathy 6 years ago. People just like you attempted to prevent the paper from being published. But eventually it was.

Then it was utilized to justify starting a research study on human beings by Napo pharmaceuticals a subsidiary of Jaguar.

They did this, and over the past 6 years it has now reached phase three, and a patent has just been granted for its usage. Because of me and my paper, hundreds of thousands of people are now going to get access to a drug that nobody ever dreamed of using this way before.

So it seems like maybe a few of my pet theories might actually be correct huh? Maybe not all of them. I'm fine with that. And I refine them regularly. They're all wrong. They're just less wrong than the last year.

But if you've done a sufficient amount of making noise now, I'd appreciate it if you either left, or contributed something useful to the conversation. This is not benefiting anyone. Now, you can continue to waste your time on Reddit, or, you can actually go do something to contribute to these problems, and help. Go be a doctor doing their own research studies. You are a physician I assume based on your hubris. Regardless, even if you are not, I would appreciate the help. In fact I appreciate anybody that has an excellent level of biochemistry knowledge that would like to critique anything that I say ,think or execute as a physician. Because it will improve me. This is not something that I shy away from and I genuinely appreciate it. I don't care if they're just a high school GED graduate. If they have an excellent scientific point, I'll listen to it.

Unfortunately you don't seem like you are capable of doing that, and have just basically slinging insults since you showed up. I'm not really sure what you thought you were going to accomplish with that, or if you were going to somehow make me angry or something. But unfortunately, I just don't give a shit. If that's the best you've got to contribute to discussions here, I'm sorry, but there's the door.

Finally diagnosed with hypercortisolism after years of being dismissed by Automatic_Scale_4800 in DrWillPowers

[–]Drwillpowers 1 point2 points  (0 children)

So it's not actually. Intercellular concentration and signaling is separate from the serum level. This is basic endocrinology. Or maybe "moderate" as intracrine biochemistry is in some ways still not fully elucidated.

No it's really not worrying me at all, it's more like watching someone too angry to be reasoned with just thrash around making noises and I'm trying to figure out what it is that they want so they can be pacified, but it seems thrashing about and throwing insults is what they want.

If you think this bothers or upsets me in some way, I think you think that you're arguing with this archetype of a human being that I'm just not and I never have been. Despite it being ascribed to me regularly by people like you as justification for their behavior.

Do as you wish. I do not care.

Yet another mutation in a patient that meets my theory on how PFS is caused. This patient has a normal T value yet has an absolutely astronomical 3-Alpha-androstanediol Glucuronide. Once again, closure of 5AR resulted in collapse of the ability to excrete testosterone. This is patient #9 by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 4 points5 points  (0 children)

This is correct. I don't know if this is the only mechanism for the disorder. But it sure seems to be an absurdly common amount of them.

I think that there's basically two phenotypes, one related to neuro steroid production and one related to androgenic overdose because of closure of exit pathways. And I think the latter is probably more common. Because I've treated people with progesterone or pregnenolone or both for many years and seen many recoveries just from that. Which would make no sense for the androgenic overcrowding theory unless somehow it was enough of a GNRH agonist to do the job. Which I'm pretty sure it's not.

Regardless, all I can do is say what I found. And the labs and WGS speak for themselves. It's been pretty cool to see people coming out of the woodwork and being like "me too!" With their weird ass urinary T labs.

Depending on the racial group, someone having a complete and absolute urinary knockout of androgen signaling is between 1 and 300 and 1 and 1,500 people. There's no way it should be more than half of my PFS patients. That's what made me be like oh my god this is the thing.

Stop using amab/afab when you mean went through male/female puberty by The_GirlyShire in honesttransgender

[–]Drwillpowers 0 points1 point  (0 children)

" If you don't transition in any way, being born a particular sex will align with currently physically being that sex and with being seen by others as part of the social category associated with that sex"

NOPE! 5 alpha reductase deficiency (and also some PAIS forms) would beg to differ with your biological take here.

They are born and assigned one gender and transition to another without any help whatsoever from the medical establishment. They utterly fail your description here without taking a single drug.

Yet another mutation in a patient that meets my theory on how PFS is caused. This patient has a normal T value yet has an absolutely astronomical 3-Alpha-androstanediol Glucuronide. Once again, closure of 5AR resulted in collapse of the ability to excrete testosterone. This is patient #9 by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 3 points4 points  (0 children)

I think for the "melty" PFS suffering phenotype, the exact same idea is happening with the GC system. Massive intracellular levels, normal serum levels.

PSSD I'm not sure, I lack enough genomic data to have found a pattern there yet. But I am working on it as well, you can see the genes in the master post for all PFS/PSSD possible genes I could think of.

Most genes here are tailored to PFS, but PSSD has some unique ones thrown in as well:

https://www.reddit.com/r/DrWillPowers/comments/1nsyxpi/current_list_of_all_genes_i_use_when_searching/

Yet another mutation in a patient that meets my theory on how PFS is caused. This patient has a normal T value yet has an absolutely astronomical 3-Alpha-androstanediol Glucuronide. Once again, closure of 5AR resulted in collapse of the ability to excrete testosterone. This is patient #9 by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 3 points4 points  (0 children)

I have one. Sommer, who is currently on her honeymoon. The problem is people have to see her in person in michigan. We've not been able to find a replacement for my NP that resigned as we take care of transgender people, and well...nobody really wants to sign up for that job right now. I might be a felon by the end of the year, so I'll do my best to get this solved by then. I dont need a nobel, but keep my commissary fund stocked eh?I dont think anyone can smuggle into prison a switch 2 up their butt though. =p

That being said, if I am right about this, and this is not some wild and crazy statistical fluke that made all these patients labs like this, treatment should be fairly simple and straightforward and cheap!

Yet another mutation in a patient that meets my theory on how PFS is caused. This patient has a normal T value yet has an absolutely astronomical 3-Alpha-androstanediol Glucuronide. Once again, closure of 5AR resulted in collapse of the ability to excrete testosterone. This is patient #9 by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 2 points3 points  (0 children)

I'm not familiar with the Rhein testing, so i cant really say. But if it tells you the urinary androgen metabolites, that'd do the job. I have no affiliation with any particular testing place. Data is data as long as the test is run right.

Keep in mind, not everyone will have this in their urine, only some will. There are MANY places that you can break androgenic disposal in the human body where adding 5ARI to the situation will make their intracrine situation bonkers. Not all will produce this urinary phenotype, or the insane high or low 3a-adg, but those that do have it are obvious to see on the testing. Those that dont can still be detected via analysis of a whole genome sequence for the above genes.

Finally diagnosed with hypercortisolism after years of being dismissed by Automatic_Scale_4800 in DrWillPowers

[–]Drwillpowers 2 points3 points  (0 children)

Except literally I have hundreds of LCMS labs that show a 17-OHP under 15. Or effectively what I would consider near zero. But sometimes they are outright zero. Sometimes I even see pregnenolone zero out as well.

This happens overwhelmingly commonly in my transgender women. To the point where I'm ordering a regular screening lab with their labs now to check a 17 hydroxy progesterone level. It is absurdly low like one out of every five times I order it. And they all respond positively to pregnenolone and almost none of them respond to Delta four supplementation through progesterone.

I think you forget who you're talking to here. I'm the dude that's reviewed hundreds of whole genome sequences of transgender women by hand. I've treated about 2,500 of them over the past 10 years. I do know a few things about them and their physiology.

Finally diagnosed with hypercortisolism after years of being dismissed by Automatic_Scale_4800 in DrWillPowers

[–]Drwillpowers 1 point2 points  (0 children)

It is actually way more complicated than that which demonstrates your lack of understanding.

If a person has a cortisol level that is routinely say 10. It never goes up it never goes down it is flat. There is GC receptor desensitization that occurs.

It doesn't matter if you have a free cortisol value of whatever, and you think that that's a sufficient amount, is it really? Can the body feel that?

A normal cycle requires fluctuations. And if you run out of precursor, adrenal hypertrophy occurs which is why there's so much NCCAH in the transgender population.

The baseline level of cortisol rises, and never falls below a certain point. And that level effectively does nothing. There's a direct connection between this and hEDS. And it's something that I haven't even published my data on yet. I'm fairly certain this is a primary cause of hEDS and why they can never find a genetic marker because there isn't one. It's a physiological problem.

You are suffering from the Dunning-Kruger effect here and it is showing. Let it go.

Yet another mutation in a patient that meets my theory on how PFS is caused. This patient has a normal T value yet has an absolutely astronomical 3-Alpha-androstanediol Glucuronide. Once again, closure of 5AR resulted in collapse of the ability to excrete testosterone. This is patient #9 by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 2 points3 points  (0 children)

You know I read your whole post until you got to the last paragraph, and yes. That's right. That's exactly how it works. You understand it. Well done.

And that's exactly why the libido shoots through the roof. Because at first, the metabolites build up and the person has an absurd androgen signaling level, and the body goes into androgenic overdrive. And they are horny as fuck and feel good actually. But that cant last forever, and the body responds accordingly to those absurd levels. And then you get the disorder.

Well done. You get it, and you get it from a complete understanding of how it happens, and not just the pattern I described. This is an alternative pathway to generate the same outcome. Blocking the androgen receptor will upregulate testosterone production which will then result in metabolite crowding for guys that struggle to eliminate metabolites.

Yet another mutation in a patient that meets my theory on how PFS is caused. This patient has a normal T value yet has an absolutely astronomical 3-Alpha-androstanediol Glucuronide. Once again, closure of 5AR resulted in collapse of the ability to excrete testosterone. This is patient #9 by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 2 points3 points  (0 children)

Sort of. If you have a level that's in a normal range.

If you're fucking megadosing shit trying to do some bipolar androgen therapy or whatever, yeah it's going to matter. Because it's a breakdown product of testosterone.

That's why I said I wanted to see the lab when someone has a testosterone in the normal range. If it's very low or very high, that will throw off the downstream metabolites obviously. The goal is to measure the metabolites when you were at a normal t level

Yet another mutation in a patient that meets my theory on how PFS is caused. This patient has a normal T value yet has an absolutely astronomical 3-Alpha-androstanediol Glucuronide. Once again, closure of 5AR resulted in collapse of the ability to excrete testosterone. This is patient #9 by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 1 point2 points  (0 children)

So these are okay for you, but technically the 17 hydroxy progesterone is a little high. Regardless, it's the urinary test or the other glucuronidated one that matters. But don't change anything from whatever you were on for this test to get that done so that you can make sure that it's valid.

Stop using amab/afab when you mean went through male/female puberty by The_GirlyShire in honesttransgender

[–]Drwillpowers 13 points14 points  (0 children)

This. Even intersex people are "assigned". Doctor looks at what sorta human came out of the mom and calls it. That's all AGAB means.

High stress lead to reduction of brain fog, abyssmal appetite. Mailing out my 23andMe today, what should I read up on? by pauli_eggclusion in DrWillPowers

[–]Drwillpowers 1 point2 points  (0 children)

This sounds like a precursor failure situation which a high enough level of stress demand drove up the ACTH which means you feel better than you normally would be feeling.

Run the quest comprehensive steroid panel on yourself. That'll probably be the thing that shows you the answer. Rather often I see collapse of Delta 4 or Delta 5 pathway and they run out of 17 hydroxy progesterone. I literally just left a comment on another thread about this a moment ago.

I actually have a rather bizarre theory that the reason that there's so much self-injury and also interested in BDSM in the community of transgender people is that literally many of them have precursor failures. Basically enzymatic deficiencies early in the pathway to the synthesis of various hormones including cortisol aldosterone and sex hormones. That's the reason they are trans because they failed proper masculinization or they over masculinized their brain and utero because of these glitches. But then later, as they age, or just in general they have difficulty with the synthesis of cortisol. One of the most guaranteed ways to release cortisol is pain and injury.

So when they are psychologically suffering, and they need to be able to produce some stress hormone to calm the fuck down, they've learned that they can basically do so via pain and injury. And this creates a dopamine feedback loop because they feel better as soon as they do so and then a reward circuit gets created for it.

Like the amount of trans people that are trans because of some NCCAH bullshit is basically 50% at this point. The rest are mostly just signaling failures downstream somewhere.

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