re your #7, we've been giving progesterone for like 4 decades at the compounding pharmacy where I work, and we've been talking about its metabolism to allopregnanolone for about 20 years.
Notably, the route of administration MATTERS. A fraction of oral progesterone certainly seems to get metabolized to allopregnanolone and have -pam like effects, so a lot of HRT docs will write oral progesterone for bedtime administration as it seems to help with calming prior to sleep (it's -pam like, as you lay out, so it's not dissimilar from giving a z-drug for sleep pharmacologically).
topically administered and injected progesterone doesn't really seem to have comparable effects, likely due to bypassing the portal circulation and thereby the first-pass effect. At least that's how this works in my head. The standard of evidence in compounding land is a little lower than in big PhRMA manufacturing land.
Progesterone is also really cheap (at least in comparison to the insanity of brexanolone IV).
re your #7, we've been giving progesterone for like 4 decades at the compounding pharmacy where I work, and we've been talking about its metabolism to allopregnanolone for about 20 years.
Notably, the route of administration MATTERS. A fraction of oral progesterone certainly seems to get metabolized to allopregnanolone and have -pam like effects, so a lot of HRT docs will write oral progesterone for bedtime administration as it seems to help with calming prior to sleep (it's -pam like, as you lay out, so it's not dissimilar from giving a z-drug for sleep pharmacologically).
topically administered and injected progesterone doesn't really seem to have comparable effects, likely due to bypassing the portal circulation and thereby the first-pass effect. At least that's how this works in my head. The standard of evidence in compounding land is a little lower than in big PhRMA manufacturing land.
Progesterone is also really cheap (at least in comparison to the insanity of brexanolone IV).