21/11/2025
Oral Estradiol-When swallowing an estradiol pill, it travels into the stomach and gut and is absorbed into the blood supply connected to the liver. Before it can reach the rest of the body, almost all of the estradiol passes through the liver first—this is called the “first-pass effect.” The liver breaks down a big part of the hormone right away, which means some is lost before it gets to the rest of the body. This also causes the liver to change the hormone into other forms and affects things like blood clotting proteins and inflammation markers in the blood.
Transdermal Estradiol
Transdermal estradiol is delivered through the skin as a patch, gel, cream, or spray. Here, the hormone is absorbed right through the skin and directly into the blood vessels just below. This path lets estradiol skip the liver the first time it enters the body—there’s no first-pass effect. Only after circulating through the whole body does some estradiol later pass through the liver, but at a much lower concentration, like any other healthy hormone made by your body.
Estradiol Injections
With injected estradiol (intramuscular or subcutaneous shot), the hormone goes straight into the blood (or muscles) and then is spread around the body. Like with transdermal delivery, it doesn’t go through the liver right away, so it avoids the first-pass effect. The liver processes the hormone only after it’s been used by tissues all over the body, just like the natural hormone your body makes.
