[11] Due to its estrogenic activity, estradiol has antigonadotropic effects and can inhibit fertility and suppress sex hormone production in both women and men.

[44][14][45] It is also used to restore estradiol levels in adult premenopausal women with hypogonadism, for instance those with premature ovarian failure or who have undergone oophorectomy.

[49][52] Estrogens are effective in the treatment of prostate cancer by suppressing testosterone levels into the castrate range, increasing levels of sex hormone-binding globulin (SHBG) and thereby decreasing the fraction of free testosterone, and possibly also via direct cytotoxic effects on prostate cancer cells.

[53][54][55] Parenteral estradiol is largely free of the cardiovascular side effects of the high oral dosages of synthetic estrogens like diethylstilbestrol ad ethinylestradiol that were used previously.

[72][73][74][75][76] Both polyestradiol phosphate monotherapy and pseudopregnancy with a combination of high-dosage intramuscular estradiol valerate and hydroxyprogesterone caproate have been assessed for this purpose in clinical studies.

[84][85][86] Estradiol is available in a variety of different formulations, including oral, intranasal, transdermal/topical, vaginal, injectable, and implantable preparations.

[11][101] An ester may be attached to one or both of the hydroxyl groups of estradiol to improve its oral bioavailability and/or duration of action with injection.

[115][114][116][110] The higher risk of VTE with oral estradiol can be attributed to the first pass and a disproportionate effect on liver synthesis of coagulation factors.

[11][117] Even high doses of parenteral estradiol, such as high-dose polyestradiol phosphate, have minimal influence on coagulation factors, in contrast to oral estrogen therapy.

[121] Conjugated estrogens and ethinylestradiol are thought to have a higher risk of VTE than estradiol because they are resistant to hepatic metabolism and have a disproportionate influence on liver production of coagulation factors.

[111][128] Hormone therapy for transgender women likewise is associated with a lower risk of VTE than birth control pills containing ethinylestradiol and a progestin.

[34] Due to health risks observed with the combination of conjugated estrogens and medroxyprogesterone acetate in the Women's Health Initiative (WHI) studies (see below), the US Food and Drug Administration (FDA) label for Estrace (estradiol) advises that estrogens should be used in menopausal hormone therapy only for the shortest time possible and at the lowest effective dose.

[20] When used to treat menopausal symptoms, the FDA recommends that discontinuation of estradiol should be attempted every three to six months via a gradual dose taper.

[138][139][140] In late pregnancy, the body produces and secretes approximately 100 mg of estrogens, including estradiol, estrone, and estriol, per day.

[138] Doses of estradiol of as high as 200 mg per day by intramuscular injection for several weeks have been administered to humans in studies.

[141][142] Serious adverse effects have not been described following acute overdose of large doses of estrogen- and progestogen-containing birth control pills by small children.

[103][102] Inducers of cytochrome P450 enzymes like CYP3A4 such as St. John's wort, phenobarbital, carbamazepine and rifampicin decrease the circulating levels of estradiol by accelerating its metabolism, whereas inhibitors of cytochrome P450 enzymes like CYP3A4 such as erythromycin, cimetidine,[143] clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice[144] may slow its metabolism resulting in increased levels of estradiol in the circulation.

[154] The ERs are expressed widely throughout the body, including in the breasts, uterus, vagina, fat, skin, bone, liver, pituitary gland, hypothalamus, and other parts of the brain.

[160][13][53][54][55][25][26] At sufficiently high dosages, estradiol is a powerful antigonadotropin, capable of suppressing testosterone levels into the castrate/female range in men.

[163] Mean integrated levels of circulating estradiol in premenopausal women across the whole menstrual cycle have been reported to be in the range of 80 and 150 pg/mL, according to some sources.

[169][170][11][179] Estramustine phosphate is also an estradiol ester, but with a nitrogen mustard moiety attached, and is used as a cytostatic antineoplastic agent in the treatment of prostate cancer.

[170][169][210][211] Due to poor absorption and low potency relative to other estrogens, oral estradiol was not widely used as late as the early 1970s.

[11][6] Studies in the 1960s showed that micronization of steroids such as spironolactone and norethisterone acetate improved their absorption and oral potency by several-fold.

[232][233][234][231] More than 15 attempts were made at development of an estradiol-containing birth control pill starting in the 1970s, but were unsuccessful due to unacceptable menstrual bleeding patterns.

[235] Subsequently, estradiol valerate/dienogest (Natazia, Qlaira) was marketed as a birth control pill in 2008[236] and estradiol/nomegestrol acetate (Naemis, Zoely) was introduced in 2012.

[170][237] Examples of major brand names in which estradiol has been marketed in include Climara, Climen, Dermestril, Divigel, Estrace, Natifa, Estraderm, Estraderm TTS, Estradot, Estraheal,[240][241] Estreva, Estrimax, Estring, Estrofem, EstroGel, Evorel, Fem7 (or FemSeven), Imvexxy, Menorest, Oesclim, OestroGel, Sandrena, Systen, and Vagifem.

[237] It is available in combination with norethisterone acetate under the major brand names Activelle, Cliane, Estalis, Eviana, Evorel Conti, Evorel Sequi, Kliogest, Novofem, Sequidot, and Trisequens; with drospirenone as Angeliq; with dydrogesterone as Femoston, Femoston Conti; and with nomegestrol acetate as Zoely.

[237][244][245][170][176][failed verification] Shortages of estradiol began around 2022, caused partly by the COVID-19 pandemic disrupting supply and due to increasing demand.

[253] In addition, topical creams that contain estradiol are generally regulated as cosmetics rather than as drugs in the US and hence are also sold over-the-counter and may be purchased without a prescription on the Internet.

[170][255][256][257][258] However, an estradiol subcutaneous implant with the brand name Meno-Implant (Organon; 20 mg) continues to be available in the Netherlands.