Acetals like THP ethers hydrolyze easily under acidic conditions, which means that orally taken THP ethers of anabolic steroids will hydrolyze already in the stomach. This sets free the anabolic steroid, while it still has to pass the intestinal track and the liver. So there will be time and opportunity for metabolic transformation of the steroid to inactive metabolites.
A THP ether also can be given parentally, but the THP steroid derivative itself is not active. When the derivative does not pass the stomach, the THP ether group has to be removed in a different way. In the blood and in muscles the pH is neutral and under these conditions THP ethers are stable compounds. We also do not have enzymes in the blood, which can hydrolyze THP ethers, as is the case with esters.
However, cytochrome P450 enzymes can oxidize THP ethers in the liver. This oxidation takes place in the ring next to the O-atom. The oxidation product then decomposes spontaneously to a dialdehyde and the free steroid (see Scheme 3). This scheme is a bit speculative, because little has been published about the metabolism of THP ethers
The free steroid will be converted in the liver to glucuronates or sulfate esters. The free steroid also may be inactivated through bonding to Sex Hormone Binding Globuline. Probably only a small part of the steroid will reach the muscle cell.
There is a clear difference between esters and THP-ethers of anabolic steroids. Esters are given parentally and after a slow release in the blood, enzymes will hydrolyze them to the active anabolic steroid. Orally taken THP ethers will hydrolyze already in the stomach. Parentally given THP ethers are oxidized in the liver and the active steroid is set free there.
As orally taken THP ethers are already hydrolyzed in the stomach, it does not make much difference when you take the anabolic steroids itself or its THP ether. The marketing of an anabolic steroid as its THP ether probably has more to do with avoidance of patents or law regulations than with the making of better or longer lasting anabolic compounds.
-taken from chapter on ethers from the anabolics book.