Reply to thread

Progesterone is characterized as "a known competitor for 5 alpha-reductase"[R]. This is the only mechanism I've come across for its reduction of 5ar activity.

I consider oral delivery to be rather unpredictable: "The metabolism of progesterone is complex, and it may form as many as 35 different unconjugated metabolites when it is ingested orally."[R] "Sedation and cognitive and memory impairment with progesterone are attributable to its inhibitory neurosteroid metabolites. These metabolites occur to a greater extent with oral progesterone, and may be minimized by switching to a parenteral route."[R]

I find injected and topical progesterone to be calming, whereas oral pregnenolone and topical DHEA both provoke significant anxiety. "Progesterone, through its neurosteroid active metabolites such as 5α-dihydroprogesterone and allopregnanolone, acts indirectly as a positive allosteric modulator of the GABA-A receptor."[R] DHEA, DHEA-S and pregnenolone sulfate are all negative allosteric modulators of the GABA-A receptor. It's unclear why I don't have problems with oral DHEA, which I assume is largely converted to DHEA-S, supposedly having a similar negative effect on the GABA-A receptor.