Progesterone Megadoses Might Be A Cheap Zulresso Substitute

https://astralcodexten.substack.com/p/progesterone-megadoses-might-be-a

Earlier this week we talked about Zulresso, a new medication for post-partum depression. It works well, but it can only be administered at a few special hospitals, and costs $35,000 per treatment.

But Zulresso is a natural metabolite of the female hormone progesterone. What’s stopping people from taking progesterone, waiting for their bodies to metabolize it into Zulresso, and saving $35,000 and a hospital stay?

As far as I can tell, nothing.

Andreen et al give some people a dose of 20 mg progesterone, then measure allopregnanolone levels. They find that the progesterone gets converted into allopregnanolone, with a max plasma concentration of about 8 nmol/L. This is about a fifth of allopregnanolone levels during pregnancy, which a course of Zulresso is trying to match. So in theory (and assuming simple pharmacokinetics) a dose of 100 mg progesterone ought to give the same peak level of allopregnanolone as a Zulresso infusion.

The only people I can find who take this to its logical conclusion are Barak & Glue. They do the same calculation as above much more rigorously, and suggest that the following progesterone regimen would correspond to the typical Zulresso infusion: