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shanemcretro · 1 month

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Me, Myself and Progesterone

I touched on progesterone (P4) in my last transgender update post. I am not quite sure if progesterone is working in the way I want it to. My biggest annoyance with it is feeling like my brain is on fire just before trying to sleep.

Rewind to late February 2024, for almost three weeks my progesterone dose was doubled to 400 mg of oral, micronised, compounded progesterone – 200 mg twice a day. That’s up from the 200 mg once at night.

I had also ceased finasteride. And finasteride interferes with the progesterone (oral) pathway conversion to neurosteroids such as allopregnanolone. This is because finasteride blocks *most* of the activity (~70%) of the 5-alpha reductase (5AR) enzyme. In turn, reducing levels of allopregnanolone – or at least slowing their conversion to neurosteroids.

My sleep quality has been pretty broken for a while now. Look at those orange blocks. And here I was looking forward to some of the benefits from progesterone. Anxiolytic? Yes please! Sleep improving? Definitely!

Instead I get this whole brain fire thing and feel like I’ve taken an anxiogenic. That got me thinking, brain on fire? Throw in some formication and it’s what feels like a glutamate rebound or surge. Excitotoxicity perhaps?

I’ve experienced similar feelings while withdrawing from pregabalin (decreases glutamate levels) and trusty old diazepam (increases GABA levels). Definitely that same feeling though. It appears that taking what I would consider a small dose (2 mg) of diazepam negates the insomnia pretty well. Even though diazepam isn’t a terribly good choice for sleep. It takes me from being a wired insomniac to sleeping beauty in about an hour.

Another interesting side effect I am seeing a lot more of is dissociation. Ordinarily, I would only experience this while in high stress, high anxiety situations but recently I’m noting it a lot more just doing chores around the house – which is a little concerning.

Regardless, it seems that something is messing with my GABAergic system and metabolites of progesterone fit the bill. Armed with my two-thirds of a biomedical science degree I went digging for more information on the metabolites. Up above is an image from my last health blog post. Note the action of finasteride on progesterone – blocking allopregnanolone (THP) and isopregnanolone.

I wonder if moving to a more potent 5AR blocker, such as dutasteride, would reduce the side effects of a higher dose of progesterone? A question for my endocrinologist I suppose. I restarted my finasteride to at least partially block some of the following progesterone metabolites. Let’s look at the metabolites a little closer and how they act.

Allopregnanolone (Tetrahydroprogesterone or THP) Positive allosteric modulator 9 hours

Pregnanolone Positive allosteric modulator 1 – 3.5 hours

Isopregnanolone Negative allosteric modulator 14 hours Targets allopregnanolone only

Epipregnanolone Negative allosteric modulator Half-life unknown

Alright, so a bunch of neurosteroids are doing a bunch of things. A few are being blocked, but also produce negative side effects when they weren’t blocked. Hormones are messy. Where does that leave me? I guess I am left questioning whether I should be taking progesterone at all. At minimum a dose reduction is definitely called for. I will probably return back to 200 mg and see what symptoms, if any, follow.

My search revealed some interesting data with overlap in symptoms shared with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) in cisgender women.

PMDD is believed to be caused by fluctuations in gonadal sex hormones or variations in sensitivity to sex hormones.

If sensitivity to level shifts is reason for the negative side effects, then single or even twice daily doses are probably not enough to smooth out the levels of neurosteroids for me, allowing me enter a withdrawal state, perhaps? Brain on fire? This paper offers some great insight into the mechanisms behind it all with some interesting side notes on SSRIs.

Interestingly, SSRIs increase allopregnanolone levels in the brain, rapidly and at low doses, as demonstrated in rodents as well as in patients with depression.

Could this be one of the reasons why I can’t tolerate SSRI/SNRIs? At the very least, it’s some food for thought. Worth noting that the original study has been questioned a little further along in the paper. Let’s circle back to those progesterone levels again. From Wikipedia

Progesterone levels tend to be less than 2 ng/mL prior to ovulation and greater than 5 ng/mL after ovulation.

What were my most recent levels again? 9.1 nmol/L or should I say 2.6 ng/mL (freedom units). That’s at 200 mg once daily at night, measured in the trough. I really need to ask myself, do I want to have symptoms of PMS/PMDD? Is that even a question that needs to be asked?

Looking at the levels on Table 1 in this paper give an idea where my levels line up. If you factor in the short half-life of most of the metabolites, once daily dosing is probably a bad idea. Ideally, I should look into getting the dose split to 100 mg twice daily.

Of course I have to be mindful of negative risk such as the androgen backdoor pathway. This has the potential to generate unwanted androgens like DHT – which will affect the hair on my head. That’s why the finasteride is here to stay until most means of testosterone generation is removed from my system…

It’s not all bad though. Finasteride competes with progesterone for the 5AR enzyme – which results in even less 5AR being available for testosterone -> DHT conversion. Another point worth considering is that progesterone has a positive effect on bone-building cells (osteoblasts). This can help with avoiding or reducing effects of osteoporosis.

Touching on side effects I’ve noticed, Progesterone should increase libido. Which is something I do not want due to past trauma. However, I wonder if the finasteride side effects are at play here. Again, I don’t consider them negative side effects either.

Other oddities I’ve also noticed my facial hair has become darker at the higher progesterone dosing at 400 mg. My upper lip now has dark black hairs, that’s new and unwanted. It might be useful for IPL treatment. But now there’s shadow on my upper lip I never had before. It isn’t just the thinning of skin either. The hairs are black instead of blonde.

One big uncertainty is that I’m not sure what my levels of estradiol will be at the next blood test. Are the 200 mg of pellets doing their job properly? Or did they fail? Does the dose need to be increased?

For now, I’ve been supplementing the implant with the remainder of my 2 mg estradiol pills while the pellets stabilise. One pill gives me ~85 pmol/L in estradiol levels. I’ve only just ran out of those so now I’m adding in some of the estradiol gel (Sandrena branded). These gave ~200 pmol/L estradiol per dose according to my most recent blood tests. In theory with one a day, I should be guaranteed to be in the late follicular phase – regardless of the implant levels.

Anyway, that was one heck of an info dump. I think that sums everything up that has been on my mind lately.

TL;DR 400 mg oral progesterone makes my brain go on fire. Progesterone metabolite levels shifting around are very activating for me. I will now target cisgender progesterone levels in the late follicular phase. Hormones are complicated. One size fits most seems to be at play when it comes to progesterone. Nothing like some trial and error! 🙃

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zillychu · 2 months

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I've seen a couple people saying they're jumping ship for [other big socmed] after the AI announcement here, but like. Guys. Friends. You do realize all the other sites have been silently working with big AI companies for a while now. Bluesky has not implemented any acknowledgement or protection, and the CEO worked with crypto for years. They're just not broadcasting it or giving you an option to help remove your work from automatic scraping. Cohost has implemented similar levels of prevention compared to Tumblr.

I greatly prefer the transparency and the tiny bit of protection, no matter how flimsy. Tumblr is pretty awful, but it's still better than everything else so far. Which sucks but until we burn down the plutocracy, this isn't gonna be escapable.

(Also, no Tumblr did not quietly sneak this in. They literally announced it before implementing.)

And my thoughts on the CEO being... himself.

#Tumblr #zilly squeaks #i wish Pillowfort wasn't so riddled with bugs #actually i wish Tumblr + Twitter got ethical CEOs with working brains #this isn't a 'you shouldn't leave' argument btw #just my personal feelings on it. including the worry that someone may jump from the frying pan into a fire bc Tumblr isn't perfect

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ghostdrinkssoup · 11 months

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nbc hannibal is a romcom purely because the central conflict results from hannibal not understanding his feelings for will and being a total loser about it because he’s never had a friend or been in love before which makes him act so silly and do the most insane things that will interprets being framed for murder as hannibal having something against him (as anyone would), and this series of misunderstandings is not resolved until hannibal’s ex girlfriend and former psychiatrist tells will that hannibal is so in love with him it makes him look stupid. after that will does not hesitate to break hannibal out of jail and douse himself in blood which is this show’s equivalent to the protagonist running to the airport to stop their love interest from leaving the country and marrying someone else before they’ve had the chance to confess that they’ve loved them ever since they’ve known them

#s1 from hannibal’s pov is the funniest shit ever he’s like I think I want a friend… I’ve never felt like this before…#I guess the only way to deal with this is to set his brain on fire #and then is shocked when will tells him the light of friendship won’t reach them for a million years #and spends the rest of the show trying to communicate how he feels without EVER SAYING ANYTHING DIRECTLY #the only way to do the miscommunication trope right #hannibal is literally just some guy and he’s so emotionally constipated he can’t even ask a guy out #zero swag and zero rizz but he still somehow gets will in the end #the show is a romcom !!#nbc hannibal #hannibal #will graham #hannigram #ghost speaks

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beeturtlle · 10 months

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CAN YALL SEE MY VISION

#Avatar #ATLA #avatar the legend of aang #azula #ty lee #mai #MAIZULEE #ITS THAT THEIR SHIP NAME???#OZAI'S ANGELS #POLY FIRE NATION GIRLS #they have been rotting in my brain #please

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bogcreacher · 4 months

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princesskkfish · 3 months

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BROS ON FIRE

@thegunnsara I think your Mikey is very cool and was super fun to draw

#rottmnt #rise of the turtles #rise of the teenage mutant ninja turtles #Rottmnt Mikey #His fire hair was very fun to do #My art #but not my character #I think tumblr killed the quality;-; oops #My brain is fried so the words arnt wording

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fanfic-gremlin-ft-trauma · 7 months

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To all my fellow, “Zukka in the southern water tribe” enthusiasts

#zukka #zuko x sokka #atla #zukka fanart #I just love the idea that once Sokka and Zuko stop being pining idiots in the fire nation #they start taking regular trips to the southern water tribe together #and eventually it’s a monthly thing #and that’s where Sokka (or zuko) proposes #that concept has been in my brain forever I needed to get it out

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malpracticinghomosexual · 4 months

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dr malpractice and his boy best friend

#blorbos save me #ive been rewatching house bc of the worms in my brain #it’s been two weeks and im already a few eps into season 4 what kind of mental illness is that #i love when people have soso much wrong with them and these two are sooooo insane #so have a little doodle from me to u #they’re bickering abt pop culture and the ethics of setting a patient on fire to raise their body temp #house md #medical malpractice #malpractice md #gregory house #greg house #dr house #james wilson #dr wilson #hilson #hilson fanart #house md fanart #doodle #evvy does art

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wavesoutbeingtossed · 12 days

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My brain is on fire same I can’t sleep and am thinking of this:

The way she writes about marriage/family/commitment through these different situations across the album is soooooooooo interesting.

You have a very intense first experience of it in “The Manuscript,” where it is first dangled in front of her/the narrator’s young, impressionable self as shorthand for real love in a situation that ended up being smoke and mirrors. She’s being told everything she wants to hear by someone who basically thinks it’s just foreplay. In the end, when it’s clear that the other person has no intention of actually making a life with her, it makes her feel used, but she forces herself to recalibrate and become the girl she thinks he and all the other hes want her to be. Easy breezy cool. But there’s a sense of loss in realizing those hopes were merely banter to the other.

You have the “grown up” version of it alluded to in “So Long, London” and “How Did It End?”, the years of putting in work to save a relationship and the “deflation of our dreaming leaving [her] bereft and reeling” leading to them “calling it all off.” The implication is clearly that they built a home together with plans for next steps at a point in time, but the commitment is shattered. (Obviously to me it sounds like marriage.) She’s bitter at spending her “prime” years with someone who ultimately didn’t want to be there, even if he couldn’t or wouldn’t admit it himself.

She felt like she did everything she was supposed to, but they were learning the right steps to different dances at as it were. Those dreams were at one point shared, but in the end they weren’t right for each other and she admits that, though bitterly (“I founded the club she’s heard great things about” eg the years she put in for him to help him grow up will end up benefiting his new lover, “but I’m not the one,” “you’ll find someone,” etc.). Mixed in with all this of her resentment of him wasting her youth (sacrificing herself at the altar), and his resentment of her for reasons less defined, and insinuations of betrayal in the shadows. The fantasy of the whole package disappears into the ether, yet she still has no answers as to how they got there.

Then in comes the wolf in sheep’s clothing in many of the rest of the songs, the one who promises her all those things she’s dreamed of since she was a kid instantly. After years of moulding herself to other men’s desires, someone comes in and tells her exactly what she wants to hear at the most vulnerable time of her life, as though the universe is answering her prayers, like some sort of cosmic payback for all she’s suffered, and it’s the most intoxicating drug of all. She’s gone from her wish for a family life feeling like she’s in a way being used for her body, to it being used as a chain to a relationship gone sour, to having someone put a metaphorical ring on her finger and tell her he wants to have babies with her, fuck those other guys.

In her grief and stupor, it’s too good to be true, which is exactly why she falls for it. But of course, it’s all an illusion, because this wolf is an amalgamation of the worst of all the men who came before him. He tells her everything she wants to hear not to make her dreams come true, but to make his. He takes the worst parts of these scenarios to make his move: he’ll stand by her, he’ll commit, he’ll do it out in the open under the spotlight’s glare (all things desperately lacking in her last relationship), but after he beds her he stabs her in the back in private and leaves her. He got what he wanted at the expense of her losing everything she wanted, this time as her world caved in seemingly for good. She feels like she gave up everything she thought she might have had for a chance that this is where the universe has been point her all along, only to be left broken for good (you represent the loss of my life as I knew it).

Then there are two sort of codas to this. In “But Daddy I Love Him” we get a sassier reimagining of “Love Story,” where the girl with the scarlet letter is mouthy and crass and tells everyone to go fuck themselves for cursing her in the first place, choosing her love above all else. And no, those haters can’t come to her wedding. Her daddy may have come around, but they sure can’t. Finally it seems someone is choosing her and will someday give her these things, and she’ll be able to show all the naysayers. (Also interestingly one of the more fictionally-veiled songs which ends happily vs the diaristic ones that don’t.)

Then of course there’s “So High School,” our first glimpse into what the future holds. Probably the only unabashedly happy (nay… electric?) song on the album, it’s all about reclaiming the buzz of youth (which is a whole other post) with a new lover. “Are you gonna marry, kiss or kill me? It’s just a game but really, I’m betting on all three for us two.” It’s, er, a direct nod to a certain now-infamous interview, but again, she’s staking her claim on her future, if not certain then at least hopeful again. This time the prospect doesn’t come with a “but.” It’s not, we’ll be pushing strollers but actually you’re too young. It’s not, we had these dreams for our future but actually I can’t move forward. It’s not, I’m going to promise you a ring and a baby but only until my needs are met and then I’m out. It’s, I know what I wanted and I’m not leaving, and thanks to that now she stays too.

The album dealt with the theme not at all in the way I expected, but is absolutely fascinating.

#writing letters addressed to the fire #me thinking too hard about Taylor lyrics #the tortured poets department #i have many thoughts #No brain power

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aidosaur · 7 months

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[tears of the kingdom] Rumors of Princess Zelda riding a mountainous beast with brutal tusks...

#totk #tears of the kingdom #loz #zelda #beast ganon #fanart #this quest description lit a fire in my brain and I finally just got back to it

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tiny-vermin · 15 days

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@runfreebirdrun THREATENED me at GUNPOINT to do this drawing of GAY PEOPLE (🤢🤢🤢🤮🤮🤮) KISSING (??!?!!?!??!?)

his post of the same pose is here, and the image we both drew was sent to iwcat by @kurocyou

#verms stuff #verms cr #beauyasha #caleb widogast #fire emoji #every time im like okay listen #we're gonna do some simple colours for this #my brain hears “lets go ham with rendering”#and this isnt the worst of it at least #ive gotten better at handling that urge #anyways #critical role #critical role fanart #damn i just realised i didnt give any of them accessories #whatever i do not gaf

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anewp0tat0 · 1 year

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looks like I can draw again!!

Sebastian called him "orphan" for the rest of the week.

#YEHAAAAAH MATEE GUESS IM GOING TO ANIMATION SCHOOL #IT WAS ALL WORTH IT. and now it's all over #actually this may mean I'Il be busier later... but for now- I'm back into the swing of things! kuro art; thoughts; tears; and what have you #it feels like a while since I've posted a big project so I hope I can make it up by finally getting back to the one's ive had in my WIPs!#thank god I got this thingy done. my brain is firing again so i gotta keep up #I know how to draw cars😅🙃#sorry if the eccess of screen prints is annoying I was experimenting #modern!au #kuroshitsuji #black butler #kuroshitsuji fanart #fanart #sebastian michaelis #ciel phantomhive #digital art #o!ciel #this would make a good ad but no not sponcered😌#sebastian starts vibrating

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turtleblogatlast · 5 months

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I will never be over Leo’s 4D chess play in “Many Unhappy Returns”. Like, just in general it is a spectacle to see this character who we’ve seen goofing around time and time again, who’s only sometimes decided to take things seriously, only to show him making a maneuver like that.

And here’s what gets me the most about his plan against Big Mama: he comes up with it on the spot. The second he sees that Big Mama has the solution they need, he’s already in game mode.

It is so satisfying watching the episode back when you realize his plan, because he literally sets the stage entirely for a decisive victory. He sees that the champion is a kraken, and comes up with both the solution to defeating it and a reasonable excuse to get that solution into the battle with them on the fly:

“Like your champ aaand those six guys. In fact, we don’t want this over too quickly. You should armor up those rookies. The whole shebang. Especially with these pointy helmets.”

And this is why giving him teleportation powers is perfect, too. He analyzes the battlefield and makes use of all the assets, moving pieces around to guarantee a win. It is honestly so impressive to witness and one of my favorite parts of his character.