Pharmacokinetics of estradiol
Estradiol can be administered in the form of a very long-lasting subcutaneous pellet implant. These implants are replaced once every 6 to 12 months, and can achieve high and very constant circulating levels of estradiol. They are surgically inserted by a trained physician in a medical office or clinic and can be placed into locations including the lower abdomen, lower back, buttocks, or hips. Subcutaneous implants containing 25, 50, and 100 mg estradiol for replacement usually once every 6 months are available as approved pharmaceutical medications. Up to 800 mg estradiol per implantation has been used. Pharmaceutical estradiol implants have been said to be used almost exclusively in the United Kingdom. An estradiol implant has not been approved by the FDA as a pharmaceutical medication in the United States, but hormone implants, including estradiol implants, are available as custom compounded products in this country.
Polyestradiol phosphate
Polyestradiol phosphate (PEP), sold under the brand name Estradurin, is an estrogen medication which is used primarily in the treatment of prostate cancer in men. It is also used in women to treat breast cancer, as a component of hormone therapy to treat low estrogen levels and menopausal symptoms, and as a component of feminizing hormone therapy for transgender women. It is given by injection into muscle once every four weeks.
Common side effects of PEP include headache, breast tenderness, breast development, feminization, sexual dysfunction, infertility, and vaginal bleeding. PEP is a synthetic estrogen and hence is an agonist of the estrogen receptor (ER), the biological target of estrogens like estradiol. It is an estrogen ester in the form of a polymer and is an extremely long-lasting prodrug of estradiol in the body. The time it takes for 50% of a dose of PEP to be eliminated from the body is more than two months. Because PEP works by being converted into estradiol, it is considered to be a natural and bioidentical form of estrogen. The safety profile of parenteral estradiol esters like PEP is greatly improved relative to synthetic oral estrogens like ethinylestradiol and diethylstilbestrol.
PEP was discovered around 1953 and was introduced for medical use in the United States in 1957. Along with estradiol undecylate and estradiol valerate, it has been frequently used in the United States and Europe as a parenteral form of estrogen to treat men with prostate cancer. However, it is no longer available in the United States.