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)
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).
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."
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.
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.
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."
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.
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.
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.
"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.
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.
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)
"If pregnancy doesn’t have a side effect..." that was a great laugh.
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).
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."
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?
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.
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 (?)
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."
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.
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.
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.
"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.
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.
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