Tc,
Estradiol metabolism is the same, once it reaches the bloodstream, no matter if it comes from endogenous or exogenous sources. Of course transdermal delivery bypasses first liver metabolism.
According to this estradiol patch (Estraderm) leaflet:
Metabolism
Transdermally applied oestradiol is metabolised in the same way as the endogenous hormone. Oestradiol is metabolised to oestrone, then later – primarily in the liver – to oestriol, epioestriol and catechol oestrogens, which are then conjugated to sulphates and glucoronides. Cytochrome 450 isoforms CYP1A2 and CYP3A4 catalyse the hydroxylation of oestradiol forming oestriol. Oestriol is glucuronidated by UGT1A1 and UGT2B7 in humans. Metabolic plasma clearance ranges from 650 to 900 L/(day x m²). Oestradiol metabolites are also subject to enterohepatic circulation. Oestradiol metabolites are far less active than oestradiol.
https://www.medicines.org.uk/emc/product/5838/smpcAs you can see, estriol is glucuronidated by UGT1A1, so in theory, your estriol levels are higher than expected, but that of course is not the entire picture, because the other enzyme might be doing the job.
Regarding progesterone, there is not much data. It's known that it increases UGT1A1 levels, but it's not metabolised by this enzyme.
I'm very interested in the subject of pharmacogenomics, so I'm more than glad to further investigate this. It also helps me forget my persistent depressive disorder.
I think taking Utrogestan vaginally would be a good option to bypass hepatic metabolism. It is known that both oestrogen and progesterone levels are on average 3 times higher in the liver than in the bloodstream, so usual blood tests don't show the bigger picture.
BeaR.