Estradiol (medication)

"Altrad" redirects here. For the French corporation "Groupe Altrad", see Mohed Altrad.
This article is about estradiol as a medication. For its role as a hormone, see Estradiol.

Estradiol
Clinical data
Pronunciation/ˌɛstrəˈdaɪoʊl/ ES-trə-DY-ohl[1][2]
Trade namesMany
Other namesOestradiol; E2; 17β-Estradiol; Estra-1,3,5(10)-triene-3,17β-diol
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth (tablet)
• Sublingual (tablet)
• Intranasal (nasal spray)
• Transdermal (patch, gel, cream, emulsion, spray)
• Vaginal (tablet, cream, suppository, insert, ring)
• IM injection (oil solution)
• SC injection (aq. soln.Tooltip aqueous solution)
• Subcutaneous implant
Drug classEstrogen
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityOral: <5%[5]
IM: 100%[6]
Protein binding~98%:[5][7]
• Albumin: 60%
• SHBG: 38%
• Free: 2%
MetabolismLiver (via hydroxylation, sulfation, glucuronidation)
MetabolitesMajor (90%):[5]
• Estrone
• Estrone sulfate
• Estrone glucuronide
• Estradiol glucuronide
Elimination half-lifeOral: 13–20 hours[5]
Sublingual: 8–18 hours[8]
Transdermal (gel): 37 hours[9]
IM (as EVTooltip estradiol valerate): 4–5 days[6]
IM (as ECTooltip estradiol cypionate): 8–10 days[10]
IVTooltip Intravenous injection (as E2): 1–2 hours[6]
ExcretionUrine: 54%[5]
Feces: 6%[5]
Identifiers
  • (8R,9S,13S,14S,17S)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC18H24O2
Molar mass272.388 g·mol−1
3D model (JSmol)
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=C3C=CC(=C4)O
  • InChI=1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17+,18+/m1/s1 checkY
  • Key:VOXZDWNPVJITMN-ZBRFXRBCSA-N checkY
  (verify)

Estradiol (E2) is a medication and naturally occurring steroid hormone.[11][12][13] It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women.[11][14] It is also used in hormonal birth control for women, in feminizing hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses.[15][16][17][18][19] Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.[11]

Side effects of estradiol in women include breast tenderness, breast enlargement, headache, fluid retention, and nausea among others.[11][20] Men and children who are exposed to estradiol may develop symptoms of feminization, such as breast development and a feminine pattern of fat distribution, and men may also experience low testosterone levels and infertility.[21][22] Estradiol may increase the risk of endometrial hyperplasia and endometrial cancer in women with intact uteruses if it is not taken together with a progestogen such as progesterone.[11] The combination of estradiol with a progestin, though not with oral progesterone, may increase the risk of breast cancer.[23][24] Estradiol should not be used in women who are pregnant or breastfeeding or who have breast cancer, among other contraindications.[20]

Estradiol is a naturally occurring and bioidentical estrogen, or an agonist of the estrogen receptor, the biological target of estrogens like endogenous estradiol.[11] Due to its estrogenic activity, estradiol has antigonadotropic effects and can inhibit fertility and suppress sex hormone production in both women and men.[25][26] Estradiol differs from non-bioidentical estrogens like conjugated estrogens and ethinylestradiol in various ways, with implications for tolerability and safety.[11]

Estradiol was discovered in 1933.[27][28] It became available as a medication that same year, in an injectable form known as estradiol benzoate.[29][30][31] Forms that were more useful by mouth, estradiol valerate and micronized estradiol, were introduced in the 1960s and 1970s and increased its popularity by this route.[32][33][34] Estradiol is also used as other prodrugs, like estradiol cypionate.[11] Related estrogens such as ethinylestradiol, which is the most common estrogen in birth control pills, and conjugated estrogens (brand name Premarin), which is used in menopausal hormone therapy, are used as medications as well.[11] In 2022, it was the 50th most commonly prescribed medication in the United States, with more than 12 million prescriptions.[35][36] It is available as a generic medication.[37][38][39]

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  3. ^ "Imvexxy Product information". Health Canada. 25 April 2012. Archived from the original on 6 June 2022. Retrieved 5 June 2022.
  4. ^ "Active substance: estradiol (except cream/balm/emulsion for application in female genital area)" (PDF). List of nationally authorised medicinal products. European Medicines Agency. Archived (PDF) from the original on 10 June 2022. Retrieved 10 June 2022.
  5. ^ a b c d e f Stanczyk FZ, Archer DF, Bhavnani BR (June 2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment". Contraception. 87 (6): 706–727. doi:10.1016/j.contraception.2012.12.011. PMID 23375353.
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  8. ^ Price TM, Blauer KL, Hansen M, Stanczyk F, Lobo R, Bates GW (March 1997). "Single-dose pharmacokinetics of sublingual versus oral administration of micronized 17 beta-estradiol". Obstetrics and Gynecology. 89 (3): 340–345. doi:10.1016/S0029-7844(96)00513-3. PMID 9052581. S2CID 71641652.
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  10. ^ Sierra-Ramírez JA, Lara-Ricalde R, Lujan M, Velázquez-Ramírez N, Godínez-Victoria M, Hernádez-Munguía IA, et al. (December 2011). "Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg)". Contraception. 84 (6): 565–570. doi:10.1016/j.contraception.2011.03.014. PMID 22078184.
  11. ^ a b c d e f g h i Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324. Archived (PDF) from the original on 22 August 2016. Retrieved 5 December 2016.
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  13. ^ Oettel M, Schillinger E (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. pp. 163–178, 235–237, 252–253, 261–276, 538–543. ISBN 978-3-642-60107-1. Archived from the original on 14 September 2020. Retrieved 27 November 2016.
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  23. ^ Yang Z, Hu Y, Zhang J, Xu L, Zeng R, Kang D (February 2017). "Estradiol therapy and breast cancer risk in perimenopausal and postmenopausal women: a systematic review and meta-analysis". Gynecological Endocrinology. 33 (2): 87–92. doi:10.1080/09513590.2016.1248932. PMID 27898258. S2CID 205631264.
  24. ^ Lambrinoudaki I (April 2014). "Progestogens in postmenopausal hormone therapy and the risk of breast cancer". Maturitas. 77 (4): 311–317. doi:10.1016/j.maturitas.2014.01.001. PMID 24485796.
  25. ^ Stege R, Carlström K, Collste L, Eriksson A, Henriksson P, Pousette A (1988). "Single drug polyestradiol phosphate therapy in prostatic cancer". American Journal of Clinical Oncology. 11 (Suppl 2): S101–S103. doi:10.1097/00000421-198801102-00024. PMID 3242384. S2CID 32650111.
  26. ^ Ockrim JL, Lalani EN, Laniado ME, Carter SS, Abel PD (May 2003). "Transdermal estradiol therapy for advanced prostate cancer--forward to the past?". The Journal of Urology. 169 (5): 1735–1737. doi:10.1097/01.ju.0000061024.75334.40. PMID 12686820.
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