and remains available only in a few countries. Microspheres Microspheres are microscopic spherical particles which can be used to encapsulate compounds. Estradiol is available in the form of an aqueous suspension of 1.0 mg estradiol in microspheres for use by intramuscular injection once a month under the brand name Juvenum E in Mexico. It achieves circulating estradiol levels of 163 pg/mL to 219 pg/mL in the first 3 to 12 hours following injection, which decrease to 42 to 66 pg/mL during the first 4 days post-injection and to 20 to 35 pg/mL after 8 days, with levels remaining in this range thereafter over 30 days. These estradiol levels are similar to the normal levels that occur during the early follicular phase of the menstrual cycle in premenopausal women (24 to 75 pg/mL). The elimination of the formulation follows three phases: a rapid phase in the first 2 days, a second phase during days 2 to 12 days with a biological half-life of 7 to 10 days, and a third phase in which estradiol levels remain elevated above baseline for up to 30 days. Graphs Subcutaneous injection Estradiol esters like estradiol valerate and estradiol cypionate can be given by subcutaneous injection instead of intramuscular injection. Subcutaneous and intramuscular injection of estradiol cypionate in an aqueous suspension has been found to result in levels of estradiol and other pharmacokinetic parameters (e.g., duration) that were virtually identical. Studies have shown that subcutaneous injection of closely related steroid esters in oil like the androgen esters testosterone cypionate, testosterone enantate, and nandrolone decanoate is effective and has similar pharmacokinetics to intramuscular injection as well. In addition, studies have found that many intramuscular injections are really subcutaneous injections, as individuals often do not actually penetrate deep enough to inject into muscle when attempting to perform an intramuscular injection and instead inject into the subcutaneous fat layer above the muscle. This is particularly prevalent with injections into the buttocks and in overweight and obese individuals, due to the thicker layer of fat over muscle. Subcutaneous injections of estradiol esters may be easier and less painful to perform than intramuscular injections, and hence may result in improved compliance and satisfaction with therapy. Subcutaneous implantation Estradiol can be administered in a very long-lasting form via subcutaneous implantation of pure crystalline estradiol compressed into a small solid cylindrical pellet. These pellets slowly and completely dissolve and are replaced once every