For what it's worth: my spouse has been prescribed supplemental progesterone to treat infertility, and the side effects were pretty bad - her doctor had her cut back her dose. She would have had to be *very* depressed to make the enduring the side effects worth it.
The major effect was sleep-disturbance-via-anxiety: she would wake up in a panic, confused about her surroundings, sometimes screaming for help. Then she wouldn't be able to sleep the rest of the night.
(she did not have any side effect like this when pregnant)
No, just supposing that the progesterone is normal during pregnancy, and waking up and not being pregnant/next to the baby (because it doesn't exist) WOULD be anxiety inducing.
Other people have said progesterone seems to help them sleep, which makes sense if allopregnanolone is a sedative. One possibility is that it's the withdrawal rather than the progesterone itself causing the anxiety/sleep disturbance. I wonder how she would do on 1/12th of the dose taken every 2 hours (not that this is realistic).
For me, 200mg supplement taken at night makes me fall asleep quickly after taking it, and make me much more likely to wake up in the middle of the night with a lot of anxiety. I am not prone to anxiety and had never experienced that before.
Strange: my wife takes progesterone supplements and they help her with anxiety: she was way more anxious before she started progesterone. People are complicated!
I take progesterone supplements and find it’s an extremely delicate balance. My natural levels (almost 0, my body struggles to make it for some reason) make me incredibly anxious. 100mg oral supplement makes me feel great and completely erases my anxiety. 200mg or more makes me anxious and slightly depressed.
Bodies are delightfully strange and complicated things. :)
This makes me wonder if when I was prescribed it for insomnia, the dose was too high for me because it made me very depressed. It didn't help with insomnia at all though. Trazodone did. I took DHEA once and it made me incredibly anxious (and it turns into progesterone).
Yeah, it’s very possible the supplement raised your levels too high. Another interesting thing is that some people apparently react differently to oral/topical. My doctor warned me that some people get very depressed with oral progesterone, but are fine with topical, and vice versa. Which actually makes sense after reading Scott’s posts.
Interestingly, I take DHEA daily (my levels without supplementation are nearly undetectable), and it has also done wonders for my energy and mood.
Ultimately I think bodies are just wildly finicky and unique, and I’m looking forward to the continued personalization of medicine to help understand the various reactions people have to identical substances.
The amounts given are woefully inadequate and don't even begin to cut through the estrogen dominance symptoms many women now experience given the xenoestrogens floating about the place in plastics, etc. Katharina Dalton was able to treat postpartum psychosis successfully in the (I think) 1950s using massive doses that mimic the doses the body produces in pregnancy to protect and hold the baby. Fascinating how her work was just ignored by the medical orofession.
I am wondering if your wife actually took bio-identical progesterone, or if she was prescribed a synthetic progestin such as medroxy-progesterone acetate, which would have a VERY different effect.
I also got a good laugh at this, but I think in context it's actually reasonable (if a clunky sentence).
"If pregnancy doesn’t have a side effect, I don’t think this regimen should have that side effect either."
It's not saying "pregnancy does not have a side effect" but rather "the side effects of taking a lot of progesterone should be a subset of the side effects of pregnancy, which are severe but survivable".
I agree this is the correct interpretation of the statement. But I think Scott is overconfident here. It is entirely possible for a drug to have a side effect when taken in isolation, that does not appear when the drug is taken in combination with other drugs. Pregnancy seems complicated to me, and it is probably better thought of as "progesterone plus lots of other stuff" than "just a bunch of progesterone"
I was going to say the same thing! Pregnancy has almost every possible side effect you can imagine! But sure, if people are willing to brave them for pregnancy, they might also be willing for an effective depression treatment
Maybe you're misinterpreting my sentence - I meant "for any side effect, if pregnancy doesn't have it, progesterone won't either", not "pregnancy doesn't have any side effects".
No, you can hold in your mind at the same time that your sentence makes very practical sense while also seeing the humor in the alternate interpretation.
It's like a double entendre. I assumed you were making it intentionally.
It also had me thinking "does the baby count as a side effect?"
I have taken progesterone after several pregnancies to help with post partum depression. If I recall correctly, 100 mg/day does the trick for me. The effect is immediate and astonishing: you go from terrified the baby will die any second, to feeling totally normal. Most women who do this wean themselves off it by 4-6 weeks postpartum in some way. The biggest two side effects are that it can make you very pleasantly sleepy - I can't imagine waking up to take it every two hours - and that it might keep you from losing weight/cause weight gain. In my own case, I basically just stop taking it once life is returning to normal in other ways (again, after 4-6 weeks).
FWIW I can't even begin to imagine taking as much progesterone as what is described in the trial - I think you would be drunk. There are many drs who prescribe progesterone post partum already - they probably have a lot of anecdotal insight into what works. (Just look for an NFP OB in your area, and chances are that person prescribes progesterone postpartum.)
Thanks for this story; I'd wondered how this worked right now, but I'm not close enough to PPD treatment or endocrinology to have any experience.
Do you take this as one 100 mg pill per day? Does it last a certain amount of time, or last long enough to carry you to your next dose without any dip?
I take a 100 mg pill per day, usually at bedtime because it makes you sleepy. I haven't noticed a real dip - I think from what I recall, it becomes relatively easy to forget to take it, to the dip must not be noticeable. I should also note that this is largely to *prevent* postpartum depression from ever setting in. You take it right away, certainly by day 3 postpartum. It helps with the anxiety that sets in as your hormone levels plummet - what are known as the normal baby blues - which frankly are an awful experience for most women - and it helps you sleep properly. The goal is to prevent those "normal" postpartum experiences from turning into something severe. I think the reason the technique is favored by a lot of drs who work with women who have large families (I am about to have my 8th baby) is that they recognize how truly awful the "baby blues" are, that they are so awful that they keep you from wanting to ever go through that again, and that they easily turn into much, much worse. So since the baby blues are normal, treat them before they ever show up, and basically erase the bulk of the problem.
The more I think about this, the more I think it would be great for psychiatrists and OBs to collaborate and work to prevent the conditions under which postpartum depression arises. Here is a link to my dr in Tallahassee, FL: https://www.tmh.org/provider/hugh-oliver-md-family-medicine. His name is Whit Oliver, and he is now heading the OB residency program at the hospital there, having recently retired from practice. He is extremely well-respected in Tallahassee and I cannot imagine how many babies he has delivered over the years. I don't know whether you would find it interesting to talk to a dr who has done this for years. You can tell him Angela Schwenkler sent you; I think he would remember me, but if not, mentioning that my husband is full professor in philosophy at FSU (and I also teach philosophy) would help orient his memory. Anyway, rather than just saying "find an NFP doc", I thought I would give you a specific reference. There's a lot of good to be done here.
Hmm… I didn’t have it bad enough to get diagnosed, but I definitely had a lot of ridiculous anxious thoughts about the baby, which I chalked up to hormones + sleep deprivation. I wonder if there should be a lower threshold for treatment… it doesn’t seem like getting a little extra progesterone right after pregnancy would be that weird of a thing for your body, I had no idea that was a treatment
Could female patients just take the progesterone vaginally, as it is commonly done when it's used during fertility treatments, to help with the dosing issue?
I took 200-400mg progesterone for fertility reasons without noticeable side effects (other friends found lower doses intolerable). Catholic fertility doctors are more interested in progesterone than the mainstream, and I know friends who were prescribed oral progesterone for PPD/PPA at lower doses that Scott considers here who felt it made a huge, immediate difference. Here's the major institute behind this: https://popepaulvi.com/
"If pregnancy doesn’t have a side effect, I don’t think this regimen should have that side effect either." Pregnancy absolutely has side effects, particularly with respect to clotting/thrombosis. There's a reason that medicine tends towards empiricism; humans are complicated. A lot of bad outcomes have occurred after a very smart person said, "I don't see why that would make a difference."
FWIW, I read that sentence ["If pregnancy..."] as a joke. Edit: Also, it ends with "shouldn't have *that* side effect", so any side effect of pregnancy would be unsurprising (except perhaps growing a human in your uterus).
Yes, you start by coming up with an argument for why something should be safe, then you test it and see (the things where the argument says it shouldn't be safe never get tested).
I agree that pregnancy has many side effects, I am just saying you can use it as a prior for progesterone treatment.
In case you want to make the sentence less confusing, "If pregnancy doesn't have a given side effect, I don't think this regimen should have that side effect either" might work.
I absolutely managed to misread the 'that side effect either' as 'side effects either' because sometimes my eyes skip along too quickly, wouldn't be surprised if this is happening to other people. 'given' / 'specific' etc prime the reader to read the rest of the sentence with proper context. :) (Even after fixing my reading I thought it was meant a little tongue-in-cheek.)
(Not meaning to complain about the sentence, by the way! I enjoyed the entire article quite a lot. I just happened upon this thought while reading this comment thread.)
I occasionally take a large 200 mg of progesterone dose orally at night for insomnia. It raises GABA as well as allopreg which is extremely sedative. Knocks me right out. Feel great the next morning.
The person who originally tweeted that was referring to someone on Twitter saying that Ukraine/the West should pay Russian soldiers to defect, which they did a few days later.
I'd be curious what the risk of blood clots would be. That's a risk with birth control.
Yes, I understand that these are normal levels during pregnancy, but your chemical make up changes immediately after, and I'm not sure if there is something during pregnancy that makes high level progesterone more ok.
Depends on the type of progesterone, as I understand it. The progestins used in birth control generally aren't identical to what the body produces. If you take bioidentical progesterone, the clotting risks are a lot lower, I believe. It's more expensive, however, and I'm not sure which type Scott used in his cost estimate. Minus the dispensing fee, 30 100mg capsules costs me the equivalent of around US$30 here in Canada at my local pharmacy.
Scott is DEFINITELY talking about bioidentical progesterone, not progestins (synthetic progesterone-like substances). Progesterone is converted by the liver to allopregnanolone. Progestins are not.
I was following this topic with interest as I currently have a contraceptive implant slowly releasing what I *thought* was progesterone into my bloodstream. But I checked and it’s actually a progestin called etonogestrel. Which I guess explains why I haven’t noticed any side effects.
Are the useful properties concerned here to do with it opposing oestrogen? Also I'm maybe way off base here but I vaguely remember pregnenolone having something to do with a similar pathway, is that another possible option?
I think in the UK progesterone is being introduced as a treatment to ease pregnancy, but only specifically to aid with the birth itself (?)
Personal anecdote: I went off combined birth control (estrogen + progesterone) several years ago after having been on it since the age of 12. Immediately went into a VERY steep bout of depression and anxiety, things I had never struggled with.
Doctor finally ran blood tests and figured out my progesterone levels were like 1/20th what they should be. He prescribed oral progesterone, and two things happened:
1. I got hit HARD with that -pam feeling. I learned to never, ever take it during the day, because it makes me as loopy as when I took opioids after surgery. Night time only!
2. Anxiety and depression vanished. I went from "I should maybe check myself into a hospital" to "life's great!" within the span of 36 hours.
There are limits, though. I learned that the 100mg dose is fantastic, but the 200mg dose causes all sorts of side effects. Insomnia, acne, and ironically also anxiety.
I very firmly believe that a lot of the anxiety/depression issues in the West are caused by hormone imbalances. Ever since my experience, I have encouraged friends with mental health issues to get their hormone levels checked and treat any imbalances. To date, two have been almost completely cured of life-long anxiety issues, and one has seen drastic improvements in his depression.
I'm hoping this will get more attention in coming years. It seems kind of crazy that friends spent years on psych drugs with very nasty side effects when a simple blood test revealed, "Oh, your [hormone] levels are 10x [higher/lower] than they should be. We should probably fix that."
Getting abnormally low progesterone after cruising on high exogenous progesterone from birth control pills reminds me of bodybuilders who take a lot of steroids and then lose the ability to naturally produce testosterone. Taking drugs is scary in general because the body has a lot of homeostasis mechanisms to long-term counteract whatever you are trying to adjust, even if the drug works exactly as intended in the short term.
I’m in agreement. My experience definitely made me rethink those “mostly harmless” birth control pills we toss like candy to young girls. Granted, I am an edge case, and overall birth control has been a phenomenal development for women. But I do hope doctors will start to move away from hormonal birth control as their first choice and more toward physical options, like the copper IUD.
Condoms are great. As a man I don't mind using them. They seem like the safest option by far in terms of side effects. Copper IUDs work by causing chronic inflammation in the uterus, which seems potentially bad, and they have several observed side effects.
Because of physics I think the reported 98% efficacy of condoms under perfect use is probably an underestimate due to not adequately operationalizing perfect use. If people actually use them perfectly and keep perfect track of which surfaces are potentially contaminated by sperm and don't do idiotic things like fingering her after using their fingers to remove the condom, the failure rate is probably almost zero unless it breaks. As a germaphobe shape-rotator I am really good at keeping track of which surfaces are potentially contaminated and that 2% probably did something I wouldn't do.
Plan B has significant side effects (it is basically a giant megadose of synthetic progesterone analog) and the pregnancy risk from one instance of unprotected sex between maximally fertile young people is only 1 in 20, and 20x the side effects of plan B sounds worse than the inconvenience of a very early abortion. Plan B is also about twice as expensive as 1/20 of an abortion. So on utilitarian grounds I endorse not using plan B and just risking it, unless you have reason to update 1/20 upwards (perfect timing within the menstrual cycle?)
People might find taking a Plan B pill less psychologically challenging and/or harmful than very early abortion.
Also: Your argument kind of implies that these (presumably accidental...) instances of unprotected sex keep accuring, so that the woman in question would actually have to take the Plan B pill 19 more times.
Having one instance happen where this decision needs to actually be made very likely decreases the probability it will happen again by quite a bit. So the actual comparison would probably be more like ≤5× the cost and side effects of Plan B vs 1/20 the cost and side effects of an abortion.
That seems a very high effectiveness rate for condoms. Preventing pregnancy during clinical trials we normally would put coil and vasectomy/tubal ligation at the top >1% risk of pregnancy/year, then pill, depot and patches, diaphragm at 10% risk and everything else including male and female condoms at ~20% risk.
These guys have been using Progesterone to treat PPD for years, one time mega IM injection, anytime up to 12mo postpartum. My midwife is so impressed with the results she’s seen from their patients she now keeps a multi dose vial of progesterone on hand in her office to treat her patients whose insurance wouldn’t cover the “this is off label” use.
I looked up the plasma concentration of progesterone during pregnancy, saw an upper bound of 90ng/ml, and multiplied it by 5 liters. I get 0.5mg of progesterone total in the bloodstream during pregnancy. It briefly concerned me that we are proposing to exogenously provide 200 times that. I was confused why we need 200 times that to get the same allopregnanolone level as pregnancy.
Oral bioavailability of 2.4% explains part of it.
Maybe the partitioning of progesterone between plasma and other tissues explains the rest.
If partitioning is uniform among watery tissues comprising 75% of the body, and the average woman weighs 77kg with a density of 1g/ml, she has 77*0.75=58 liters of watery tissue. 0.024 * 5/58 = 0.002 = 1/500, implying only 1/500 of the progesterone dose ends up in plasma. Orally giving people 200x the max progesterone content of their plasma during pregnancy seems totally reasonable now.
Now I am curious why we didn't evolve to gradually taper progesterone after pregnancy so we don't get PPD.
"Progesterone interferes with prolactin binding to the receptors on the alveolar cells within the breast, thereby directly suppressing milk production. The hormonal trigger for the initiation of lactation after birth is primarily the rapid decline in the level of placental progesterone."
For context: during the third trimester of pregnancy the placenta produces about 250 mg progesterone per day, which is released pretty much directly into the blood.
Oral dosing will require at least this amount (probably much more) to achieve equivalent blood serum concentrations.
katharina Dalton administered even higher doses - 20mg is not particularly high - to women suffering postpartum psychosis, to great effect. That was decades and decades ago and it appears her work lies buried too.
Oh, sorry, didn't see that, duh. No, it wasn't, it was lower, I think. I can't find the document I initially read on the net now, frustratingly. Wow, that's a lot. And fantastic to see.
I take 200mg of oral progesterone as transfemme hormone therapy, I've been on it for a while and I and a good number of other transfemmes I know have experimented with taking high doses of it recreationally.
The claim that progesterone doesn't have any side effects at the doses you're talking about is very contrary to a lot of testimonials as well as pharmacological effects that should be kind of obvious. The metabolite you're trying to maximize here is a a GABA-A receptor agonist, which is going to give it somewhat intoxicating, sedative effects heading towards nauseating and disorienting as dosage trends upwards. It can also significantly spike your libido. These aren't totally bad effects and they might even be a part of what you want for treating PPD, but saying "there's no side effects" is just not true.
There's also multiple kinds of progresterone on the market and non-bioidentical progesterone is much worse than bioidentical, when I was on it for a month it made me suicidally depressed, taking a high dose of that might be legitimately dangerous to someone's mental health.
I definitely didn't say "no side effects". I did say "shouldn't be more side effects than pregnancy", although you're right that this doesn't seem right - pregnancy isn't sedating. Maybe that's because the progesterone ramps up over a long period of time?
"But given that these are postpartum women, they’re probably getting up every two hours in the middle of the night anyway; I’m not sure having to take the progesterone makes it any worse."
Speaking as a relatively new mum, this absolutely makes things worse. When you're baby is randomly waking every two hours to feed, that is unlikely to coincide with the medication timings, and what tiny amount of sleep you're getting from "sleeping while the baby sleeps" completely goes out the window.
Yeah, also mom of an infant and those chances you get to do a full REM cycle are golden. Also, unpredictable. I’m not sure how long you’d need to keep taking the progesterone, but getting up every two hours for months is very different from a few days. I didn’t actually need to get up every 2-3 hours except the first few days. And at that point you probably aren’t going to get diagnosed with PPD serious enough to warrant drugs.
I agree, this throwaway comment was tooth-grinding. Getting up every two hours to nurse a baby put me over the edge. I could barely do it. Of course waking up just to take a pill is easier than feeding an infant, but caregiver sleep deprivation is brutal.
Since everyone seems confused about this: oral dosing is fine; normally the problem with oral progesterone is low bioavailability from first-pass metabolism, but we're not interested in the progesterone -- we're interested in the metabolites.
>You would have to be very careful to get the timing right, since the difference between causing post-partum depression and curing it comes from tapering *off* high levels of progesterone rather than crashing all at once.
It seems like Scott has promoted what was just a hypothesis in the previous post to a fact in this one off-screen.
"200–800 mg daily, doses above 200 mg to be given in 2 divided doses, for premenstrual syndrome start on day 12–14 and continue until onset of menstruation (but not recommended); rectally if barrier methods of contraception are used, in patients who have recently given birth or in those who suffer from vaginal infection or recurrent cystitis."
The NHS seems to have had it as part of their guidelines for years.
Have any american physicians considered just looking at the list of approved uses for drugs in other countries?
Its great to see another provider making this conclusion. Nice work as always. So many great things we can do in psychiatry when its physiology is understood...plus, reading what you have to say is helping me get of a rut as ive been beaten down with dogma the last few years and forgot how to think.
I read that comment and got irritated, then I read this comment and was pleased. Nice.
For what it's worth: my spouse has been prescribed supplemental progesterone to treat infertility, and the side effects were pretty bad - her doctor had her cut back her dose. She would have had to be *very* depressed to make the enduring the side effects worth it.
The major effect was sleep-disturbance-via-anxiety: she would wake up in a panic, confused about her surroundings, sometimes screaming for help. Then she wouldn't be able to sleep the rest of the night.
(she did not have any side effect like this when pregnant)
In a kind of "where is my baby?!" kind of way?
Can't tell if this is a dark joke or not, but answering seriously: it was more of a "why is my husband trying to attack me way" (I wasn't).
No, just supposing that the progesterone is normal during pregnancy, and waking up and not being pregnant/next to the baby (because it doesn't exist) WOULD be anxiety inducing.
Well at least this nicely solves the needing to wake up every two hours to take another dose thing. :P
Other people have said progesterone seems to help them sleep, which makes sense if allopregnanolone is a sedative. One possibility is that it's the withdrawal rather than the progesterone itself causing the anxiety/sleep disturbance. I wonder how she would do on 1/12th of the dose taken every 2 hours (not that this is realistic).
For example - William S Burroughs reported that after taking heroin, after falling asleep, he would often awaken later with a start.
Apologies if this is already a well-known phenomenon.
For me, 200mg supplement taken at night makes me fall asleep quickly after taking it, and make me much more likely to wake up in the middle of the night with a lot of anxiety. I am not prone to anxiety and had never experienced that before.
Strange: my wife takes progesterone supplements and they help her with anxiety: she was way more anxious before she started progesterone. People are complicated!
I take progesterone supplements and find it’s an extremely delicate balance. My natural levels (almost 0, my body struggles to make it for some reason) make me incredibly anxious. 100mg oral supplement makes me feel great and completely erases my anxiety. 200mg or more makes me anxious and slightly depressed.
Bodies are delightfully strange and complicated things. :)
This makes me wonder if when I was prescribed it for insomnia, the dose was too high for me because it made me very depressed. It didn't help with insomnia at all though. Trazodone did. I took DHEA once and it made me incredibly anxious (and it turns into progesterone).
Yeah, it’s very possible the supplement raised your levels too high. Another interesting thing is that some people apparently react differently to oral/topical. My doctor warned me that some people get very depressed with oral progesterone, but are fine with topical, and vice versa. Which actually makes sense after reading Scott’s posts.
Interestingly, I take DHEA daily (my levels without supplementation are nearly undetectable), and it has also done wonders for my energy and mood.
Ultimately I think bodies are just wildly finicky and unique, and I’m looking forward to the continued personalization of medicine to help understand the various reactions people have to identical substances.
The amounts given are woefully inadequate and don't even begin to cut through the estrogen dominance symptoms many women now experience given the xenoestrogens floating about the place in plastics, etc. Katharina Dalton was able to treat postpartum psychosis successfully in the (I think) 1950s using massive doses that mimic the doses the body produces in pregnancy to protect and hold the baby. Fascinating how her work was just ignored by the medical orofession.
I am wondering if your wife actually took bio-identical progesterone, or if she was prescribed a synthetic progestin such as medroxy-progesterone acetate, which would have a VERY different effect.
"If pregnancy doesn’t have a side effect..." that was a great laugh.
Right!?!?!?
Everything from nose bleeds, constipation to possible gestational diabetes! Easy!
I also got a good laugh at this, but I think in context it's actually reasonable (if a clunky sentence).
"If pregnancy doesn’t have a side effect, I don’t think this regimen should have that side effect either."
It's not saying "pregnancy does not have a side effect" but rather "the side effects of taking a lot of progesterone should be a subset of the side effects of pregnancy, which are severe but survivable".
I agree this is the correct interpretation of the statement. But I think Scott is overconfident here. It is entirely possible for a drug to have a side effect when taken in isolation, that does not appear when the drug is taken in combination with other drugs. Pregnancy seems complicated to me, and it is probably better thought of as "progesterone plus lots of other stuff" than "just a bunch of progesterone"
Agree. And I kinda hate to say it: but a woman would never have written that sentence.
Oh well 😂
Why not? Are women more aware of the differences between dosing a pure chemical and combinations of them?
I was going to say the same thing! Pregnancy has almost every possible side effect you can imagine! But sure, if people are willing to brave them for pregnancy, they might also be willing for an effective depression treatment
Maybe you're misinterpreting my sentence - I meant "for any side effect, if pregnancy doesn't have it, progesterone won't either", not "pregnancy doesn't have any side effects".
No, you can hold in your mind at the same time that your sentence makes very practical sense while also seeing the humor in the alternate interpretation.
It's like a double entendre. I assumed you were making it intentionally.
It also had me thinking "does the baby count as a side effect?"
Pretty sure pregnancy is a side effect of the baby!
Eh, what counts as an effect and what as a side effect is up to what you want.
Eg the main effect of viagra started as a side effect.
Similarly, Aspirin is now given to people mainly for what used to be side-effects when it was a mild painkiller.
I have taken progesterone after several pregnancies to help with post partum depression. If I recall correctly, 100 mg/day does the trick for me. The effect is immediate and astonishing: you go from terrified the baby will die any second, to feeling totally normal. Most women who do this wean themselves off it by 4-6 weeks postpartum in some way. The biggest two side effects are that it can make you very pleasantly sleepy - I can't imagine waking up to take it every two hours - and that it might keep you from losing weight/cause weight gain. In my own case, I basically just stop taking it once life is returning to normal in other ways (again, after 4-6 weeks).
FWIW I can't even begin to imagine taking as much progesterone as what is described in the trial - I think you would be drunk. There are many drs who prescribe progesterone post partum already - they probably have a lot of anecdotal insight into what works. (Just look for an NFP OB in your area, and chances are that person prescribes progesterone postpartum.)
Thanks for this story; I'd wondered how this worked right now, but I'm not close enough to PPD treatment or endocrinology to have any experience.
Do you take this as one 100 mg pill per day? Does it last a certain amount of time, or last long enough to carry you to your next dose without any dip?
I take a 100 mg pill per day, usually at bedtime because it makes you sleepy. I haven't noticed a real dip - I think from what I recall, it becomes relatively easy to forget to take it, to the dip must not be noticeable. I should also note that this is largely to *prevent* postpartum depression from ever setting in. You take it right away, certainly by day 3 postpartum. It helps with the anxiety that sets in as your hormone levels plummet - what are known as the normal baby blues - which frankly are an awful experience for most women - and it helps you sleep properly. The goal is to prevent those "normal" postpartum experiences from turning into something severe. I think the reason the technique is favored by a lot of drs who work with women who have large families (I am about to have my 8th baby) is that they recognize how truly awful the "baby blues" are, that they are so awful that they keep you from wanting to ever go through that again, and that they easily turn into much, much worse. So since the baby blues are normal, treat them before they ever show up, and basically erase the bulk of the problem.
The more I think about this, the more I think it would be great for psychiatrists and OBs to collaborate and work to prevent the conditions under which postpartum depression arises. Here is a link to my dr in Tallahassee, FL: https://www.tmh.org/provider/hugh-oliver-md-family-medicine. His name is Whit Oliver, and he is now heading the OB residency program at the hospital there, having recently retired from practice. He is extremely well-respected in Tallahassee and I cannot imagine how many babies he has delivered over the years. I don't know whether you would find it interesting to talk to a dr who has done this for years. You can tell him Angela Schwenkler sent you; I think he would remember me, but if not, mentioning that my husband is full professor in philosophy at FSU (and I also teach philosophy) would help orient his memory. Anyway, rather than just saying "find an NFP doc", I thought I would give you a specific reference. There's a lot of good to be done here.
+1 for just being a philosopher.
Hmm… I didn’t have it bad enough to get diagnosed, but I definitely had a lot of ridiculous anxious thoughts about the baby, which I chalked up to hormones + sleep deprivation. I wonder if there should be a lower threshold for treatment… it doesn’t seem like getting a little extra progesterone right after pregnancy would be that weird of a thing for your body, I had no idea that was a treatment
Could female patients just take the progesterone vaginally, as it is commonly done when it's used during fertility treatments, to help with the dosing issue?
Taking it rectally is another option that offers better absorption rates. Neither would be exactly fun to do a lot.
The former isn't that bad.
I took 200-400mg progesterone for fertility reasons without noticeable side effects (other friends found lower doses intolerable). Catholic fertility doctors are more interested in progesterone than the mainstream, and I know friends who were prescribed oral progesterone for PPD/PPA at lower doses that Scott considers here who felt it made a huge, immediate difference. Here's the major institute behind this: https://popepaulvi.com/
"If pregnancy doesn’t have a side effect, I don’t think this regimen should have that side effect either." Pregnancy absolutely has side effects, particularly with respect to clotting/thrombosis. There's a reason that medicine tends towards empiricism; humans are complicated. A lot of bad outcomes have occurred after a very smart person said, "I don't see why that would make a difference."
FWIW, I read that sentence ["If pregnancy..."] as a joke. Edit: Also, it ends with "shouldn't have *that* side effect", so any side effect of pregnancy would be unsurprising (except perhaps growing a human in your uterus).
Yes, you start by coming up with an argument for why something should be safe, then you test it and see (the things where the argument says it shouldn't be safe never get tested).
I agree that pregnancy has many side effects, I am just saying you can use it as a prior for progesterone treatment.
In case you want to make the sentence less confusing, "If pregnancy doesn't have a given side effect, I don't think this regimen should have that side effect either" might work.
I absolutely managed to misread the 'that side effect either' as 'side effects either' because sometimes my eyes skip along too quickly, wouldn't be surprised if this is happening to other people. 'given' / 'specific' etc prime the reader to read the rest of the sentence with proper context. :) (Even after fixing my reading I thought it was meant a little tongue-in-cheek.)
(Not meaning to complain about the sentence, by the way! I enjoyed the entire article quite a lot. I just happened upon this thought while reading this comment thread.)
I occasionally take a large 200 mg of progesterone dose orally at night for insomnia. It raises GABA as well as allopreg which is extremely sedative. Knocks me right out. Feel great the next morning.
What are the recurring examples of institutions accepting the brilliant rationalist stuff in that tweet at the end?
Came here to look for this too.
The person who originally tweeted that was referring to someone on Twitter saying that Ukraine/the West should pay Russian soldiers to defect, which they did a few days later.
Just to be clear I wasn't being sarcastic, huge longtime SSC fan here. Just wasn't aware of many examples of this plotline
https://thezvi.wordpress.com/2021/10/28/an-unexpected-victory-container-stacking-at-the-port-of-los-angeles/
I'd be curious what the risk of blood clots would be. That's a risk with birth control.
Yes, I understand that these are normal levels during pregnancy, but your chemical make up changes immediately after, and I'm not sure if there is something during pregnancy that makes high level progesterone more ok.
Depends on the type of progesterone, as I understand it. The progestins used in birth control generally aren't identical to what the body produces. If you take bioidentical progesterone, the clotting risks are a lot lower, I believe. It's more expensive, however, and I'm not sure which type Scott used in his cost estimate. Minus the dispensing fee, 30 100mg capsules costs me the equivalent of around US$30 here in Canada at my local pharmacy.
Scott is DEFINITELY talking about bioidentical progesterone, not progestins (synthetic progesterone-like substances). Progesterone is converted by the liver to allopregnanolone. Progestins are not.
I was following this topic with interest as I currently have a contraceptive implant slowly releasing what I *thought* was progesterone into my bloodstream. But I checked and it’s actually a progestin called etonogestrel. Which I guess explains why I haven’t noticed any side effects.
Are the useful properties concerned here to do with it opposing oestrogen? Also I'm maybe way off base here but I vaguely remember pregnenolone having something to do with a similar pathway, is that another possible option?
I think in the UK progesterone is being introduced as a treatment to ease pregnancy, but only specifically to aid with the birth itself (?)
pregnenolone is one metabolic step prior to progesterone. https://en.wikipedia.org/wiki/Pregnenolone#/media/File:Steroidogenesis.svg
This strangely reminded me of Juicero.
Personal anecdote: I went off combined birth control (estrogen + progesterone) several years ago after having been on it since the age of 12. Immediately went into a VERY steep bout of depression and anxiety, things I had never struggled with.
Doctor finally ran blood tests and figured out my progesterone levels were like 1/20th what they should be. He prescribed oral progesterone, and two things happened:
1. I got hit HARD with that -pam feeling. I learned to never, ever take it during the day, because it makes me as loopy as when I took opioids after surgery. Night time only!
2. Anxiety and depression vanished. I went from "I should maybe check myself into a hospital" to "life's great!" within the span of 36 hours.
There are limits, though. I learned that the 100mg dose is fantastic, but the 200mg dose causes all sorts of side effects. Insomnia, acne, and ironically also anxiety.
I very firmly believe that a lot of the anxiety/depression issues in the West are caused by hormone imbalances. Ever since my experience, I have encouraged friends with mental health issues to get their hormone levels checked and treat any imbalances. To date, two have been almost completely cured of life-long anxiety issues, and one has seen drastic improvements in his depression.
I'm hoping this will get more attention in coming years. It seems kind of crazy that friends spent years on psych drugs with very nasty side effects when a simple blood test revealed, "Oh, your [hormone] levels are 10x [higher/lower] than they should be. We should probably fix that."
Getting abnormally low progesterone after cruising on high exogenous progesterone from birth control pills reminds me of bodybuilders who take a lot of steroids and then lose the ability to naturally produce testosterone. Taking drugs is scary in general because the body has a lot of homeostasis mechanisms to long-term counteract whatever you are trying to adjust, even if the drug works exactly as intended in the short term.
I’m in agreement. My experience definitely made me rethink those “mostly harmless” birth control pills we toss like candy to young girls. Granted, I am an edge case, and overall birth control has been a phenomenal development for women. But I do hope doctors will start to move away from hormonal birth control as their first choice and more toward physical options, like the copper IUD.
Condoms are great. As a man I don't mind using them. They seem like the safest option by far in terms of side effects. Copper IUDs work by causing chronic inflammation in the uterus, which seems potentially bad, and they have several observed side effects.
Because of physics I think the reported 98% efficacy of condoms under perfect use is probably an underestimate due to not adequately operationalizing perfect use. If people actually use them perfectly and keep perfect track of which surfaces are potentially contaminated by sperm and don't do idiotic things like fingering her after using their fingers to remove the condom, the failure rate is probably almost zero unless it breaks. As a germaphobe shape-rotator I am really good at keeping track of which surfaces are potentially contaminated and that 2% probably did something I wouldn't do.
My experiences match yours and I also wonder about the 2% failure rate. Failures that do happen tend to be pretty obvious, so solvable via plan B.
Plan B has significant side effects (it is basically a giant megadose of synthetic progesterone analog) and the pregnancy risk from one instance of unprotected sex between maximally fertile young people is only 1 in 20, and 20x the side effects of plan B sounds worse than the inconvenience of a very early abortion. Plan B is also about twice as expensive as 1/20 of an abortion. So on utilitarian grounds I endorse not using plan B and just risking it, unless you have reason to update 1/20 upwards (perfect timing within the menstrual cycle?)
Unfortunately I live in a backwards shithole where abortion on demand is illegal.
Also, sample size of 1 but no side effects were observed.
People might find taking a Plan B pill less psychologically challenging and/or harmful than very early abortion.
Also: Your argument kind of implies that these (presumably accidental...) instances of unprotected sex keep accuring, so that the woman in question would actually have to take the Plan B pill 19 more times.
Having one instance happen where this decision needs to actually be made very likely decreases the probability it will happen again by quite a bit. So the actual comparison would probably be more like ≤5× the cost and side effects of Plan B vs 1/20 the cost and side effects of an abortion.
That seems a very high effectiveness rate for condoms. Preventing pregnancy during clinical trials we normally would put coil and vasectomy/tubal ligation at the top >1% risk of pregnancy/year, then pill, depot and patches, diaphragm at 10% risk and everything else including male and female condoms at ~20% risk.
Where does the 1% from _vasectomy_ come from?
<1% sorry, sign wrong way round. The CDC figure is 0.15% I assume from surgical failure and "recanalisation".
https://naprotechnology.com/depression/
These guys have been using Progesterone to treat PPD for years, one time mega IM injection, anytime up to 12mo postpartum. My midwife is so impressed with the results she’s seen from their patients she now keeps a multi dose vial of progesterone on hand in her office to treat her patients whose insurance wouldn’t cover the “this is off label” use.
I looked up the plasma concentration of progesterone during pregnancy, saw an upper bound of 90ng/ml, and multiplied it by 5 liters. I get 0.5mg of progesterone total in the bloodstream during pregnancy. It briefly concerned me that we are proposing to exogenously provide 200 times that. I was confused why we need 200 times that to get the same allopregnanolone level as pregnancy.
Oral bioavailability of 2.4% explains part of it.
Maybe the partitioning of progesterone between plasma and other tissues explains the rest.
If partitioning is uniform among watery tissues comprising 75% of the body, and the average woman weighs 77kg with a density of 1g/ml, she has 77*0.75=58 liters of watery tissue. 0.024 * 5/58 = 0.002 = 1/500, implying only 1/500 of the progesterone dose ends up in plasma. Orally giving people 200x the max progesterone content of their plasma during pregnancy seems totally reasonable now.
Now I am curious why we didn't evolve to gradually taper progesterone after pregnancy so we don't get PPD.
Second mystery solved:
"Progesterone interferes with prolactin binding to the receptors on the alveolar cells within the breast, thereby directly suppressing milk production. The hormonal trigger for the initiation of lactation after birth is primarily the rapid decline in the level of placental progesterone."
https://www.medscape.com/viewarticle/565623_2#:~:text=Progesterone%20interferes%20with%20prolactin%20binding,thereby%20directly%20suppressing%20milk%20production.&text=The%20hormonal%20trigger%20for%20the,the%20level%20of%20placental%20progesterone.
So this fits neatly under the "changed tradeoffs" category in Gwern's drug heuristics: https://www.gwern.net/Drug-heuristics#:~:text=escape%20his%20%E2%80%98EOC%E2%80%99%3A-,Changed%20Tradeoffs,-.%20Evolution%20%E2%80%98designed%E2%80%99%20the
People have access to formula now, which can substitute for breast milk in the rare event that someone gets PPD and needs supplemental progesterone.
Do women that formula feed from the beginning less likely to get PPD?
The opposite. A quick google search found several studies that all agree breastfeeding reduces PPD risk.
Breastfeeding releases lots of oxytocin which has antidepressant effects. So maybe that kinda substitutes for the drop in progesterone.
>and multiplied it by 5 liters
It doesn't really work like that. Most progesterone will be absorbed in fats, not circulating in the blood.
For context: during the third trimester of pregnancy the placenta produces about 250 mg progesterone per day, which is released pretty much directly into the blood.
Oral dosing will require at least this amount (probably much more) to achieve equivalent blood serum concentrations.
katharina Dalton administered even higher doses - 20mg is not particularly high - to women suffering postpartum psychosis, to great effect. That was decades and decades ago and it appears her work lies buried too.
The procedure I linked involves 7000 mg over four days, not 20 mg. Was Dalton's dose even higher than that?
Oh, sorry, didn't see that, duh. No, it wasn't, it was lower, I think. I can't find the document I initially read on the net now, frustratingly. Wow, that's a lot. And fantastic to see.
I take 200mg of oral progesterone as transfemme hormone therapy, I've been on it for a while and I and a good number of other transfemmes I know have experimented with taking high doses of it recreationally.
The claim that progesterone doesn't have any side effects at the doses you're talking about is very contrary to a lot of testimonials as well as pharmacological effects that should be kind of obvious. The metabolite you're trying to maximize here is a a GABA-A receptor agonist, which is going to give it somewhat intoxicating, sedative effects heading towards nauseating and disorienting as dosage trends upwards. It can also significantly spike your libido. These aren't totally bad effects and they might even be a part of what you want for treating PPD, but saying "there's no side effects" is just not true.
There's also multiple kinds of progresterone on the market and non-bioidentical progesterone is much worse than bioidentical, when I was on it for a month it made me suicidally depressed, taking a high dose of that might be legitimately dangerous to someone's mental health.
I definitely didn't say "no side effects". I did say "shouldn't be more side effects than pregnancy", although you're right that this doesn't seem right - pregnancy isn't sedating. Maybe that's because the progesterone ramps up over a long period of time?
Do you know what the best (or at least most typical) approach for taking it recreationally with the goal of spiking libido is?
"But given that these are postpartum women, they’re probably getting up every two hours in the middle of the night anyway; I’m not sure having to take the progesterone makes it any worse."
Speaking as a relatively new mum, this absolutely makes things worse. When you're baby is randomly waking every two hours to feed, that is unlikely to coincide with the medication timings, and what tiny amount of sleep you're getting from "sleeping while the baby sleeps" completely goes out the window.
Yeah, also mom of an infant and those chances you get to do a full REM cycle are golden. Also, unpredictable. I’m not sure how long you’d need to keep taking the progesterone, but getting up every two hours for months is very different from a few days. I didn’t actually need to get up every 2-3 hours except the first few days. And at that point you probably aren’t going to get diagnosed with PPD serious enough to warrant drugs.
I agree, this throwaway comment was tooth-grinding. Getting up every two hours to nurse a baby put me over the edge. I could barely do it. Of course waking up just to take a pill is easier than feeding an infant, but caregiver sleep deprivation is brutal.
Since everyone seems confused about this: oral dosing is fine; normally the problem with oral progesterone is low bioavailability from first-pass metabolism, but we're not interested in the progesterone -- we're interested in the metabolites.
specifically the first pass metabolites!
>You would have to be very careful to get the timing right, since the difference between causing post-partum depression and curing it comes from tapering *off* high levels of progesterone rather than crashing all at once.
It seems like Scott has promoted what was just a hypothesis in the previous post to a fact in this one off-screen.
Time release progesterone pill? Then the pharma companies can patent it and make money...
A while back you mentioned a hypothetical about russian chemists who use entirely different chemicals and nobody seems to talk to each other...
https://bnf.nice.org.uk/clinical-medicinal-product-information/cyclogest-pessaries.html#indicationsAndDoses
Indications and dose
Premenstrual syndrome,
Post-natal depression
By vagina, or by rectum
For Adult
"200–800 mg daily, doses above 200 mg to be given in 2 divided doses, for premenstrual syndrome start on day 12–14 and continue until onset of menstruation (but not recommended); rectally if barrier methods of contraception are used, in patients who have recently given birth or in those who suffer from vaginal infection or recurrent cystitis."
The NHS seems to have had it as part of their guidelines for years.
Have any american physicians considered just looking at the list of approved uses for drugs in other countries?
Its great to see another provider making this conclusion. Nice work as always. So many great things we can do in psychiatry when its physiology is understood...plus, reading what you have to say is helping me get of a rut as ive been beaten down with dogma the last few years and forgot how to think.
FWIW, FDA approved Zurzuvae (oral Zulresso) today. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression