Estradiol

Estradiol
ATC Code D11AX34, G03CA03, G03CC13, G03CD03
Formula C18H24O2
Molar Mass (g·mol−1) 272,382
Physical State solid
Melting Point (°C) 173
Boiling Point (°C) 445,9
PKS Value 10,46
CAS Number 50-28-2; 17916-67-5; 35380-71-3
PUB Number 5757
Drugbank ID DB00783

Basics

Estradiol or estradiol is a naturally occurring steroid hormone from the group of estrogens (female sex hormones). It is commercially available in various preparations. These hormone therapy products are used to treat menopausal hot flashes triggered by vulvo-vaginal atrophy, estrogen deficiency, and to prevent postmenopausal osteoporosis. In addition, the hormone is used for palliative therapy in the treatment of breast cancer and androgen-dependent prostate cancer. Estradiol, in the synthetic form ethinyl estradiol, is a component of oral contraceptives used to prevent pregnancy (birth control pills).

The drugs are administered orally, vaginally (e.g. vagninal rings) and transdermally (e.g. patches) and are sometimes combined with a progestogen.

Pharmacology

Pharmacodynamics

Estradiol acts by binding to two subtypes of the estrogen receptor: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). The hormone also has a strong agonistic effect on the G protein-coupled estrogen receptor (GPER), which is an important regulator of estradiol's rapid actions. Once bound to its estrogen receptor, the drug enters the nucleus of the target cell and regulates gene transcription and messenger RNA formation. This mRNA contacts ribosomes, which produce specific proteins that express the effect of estradiol on the target cell. Agonism of estrogen receptors enhances proestrogenic effects, leading to relief of vasomotor (involving the movement of blood vessels) and urogenital symptoms of postmenopausal or low estradiol.

Estradiol also exerts beneficial effects on bone density by inhibiting bone resorption.

Pharmacokinetics

Ethinyl estradiol differs from estradiol because of its higher bioavailability and increased resistance to metabolism, making it more suitable for oral administration.

First-pass metabolism in the gastrointestinal tract rapidly degrades estradiol tablets before they enter the systemic circulation. Therefore, the bioavailability of oral estrogens is only 2-10%. After absorption, the esters are cleaved, resulting in the release of endogenous estradiol or 17β-estradiol.

Transdermal preparations release estradiol slowly through intact skin, maintaining circulating estradiol levels over a period of 1 week. The bioavailability of estradiol after transdermal administration is approximately 20 times higher than after oral administration. Transdermal estradiol avoids first-pass metabolism effects that reduce bioavailability.

In vaginal rings and cream preparations, the hormone is efficiently absorbed through the mucous membranes of the vagina. Vaginal administration of estrogens bypasses first-pass metabolism.

More than 95% of estrogens circulate in the blood bound to sex hormone-binding globulin (SHBG) and albumin. Metabolic conversion occurs mainly in the liver and intestine. Estradiol is metabolized to estrone, and both are converted to estriol, which is later excreted in the urine.

Interactions

Estradiol is predominantly biotransformed by CYP3A4 (enzyme family), therefore corresponding drug interactions with CYP inhibitors and inducers are possible. These include anticonvulsants (e.g., phenobarbital, phenytoin, carbamazepine), anti-infectives (e.g., rifampicin, rifabutin, nevirapine, efavirenz), and St. John's wort (Hypericum perforatum).
Bei vaginaler und transdermaler Anwendung von Estradiol sind klinisch relevante Arzneimittelwechselwirkungen nicht anzunehmen, da das Hormon kaum in das Blut- bzw. Lymphsystem des Körpers aufgenommen wird.

Toxicity

Side effects

The most common possible adverse effects when used systemically include:

  • Vaginal bleeding
  • Abdominal pain, nausea
  • breast tenderness, breast enlargement, breast pain
  • Depression
  • Weight gain
  • headache, dizziness
  • cramps in the legs
  • edema
  • reactions at the site of application

Serious side effects such as ovarian cancer, liver tumors, and severe cardiovascular disease occur very rarely; this is mainly the case with longer-term therapy.

Toxicological data

NOAEL in rats at 90 days: 0.003 mg/kg/day for blood, female and male reproductive, endocrine and liver toxicity.

TDLO (lowest known toxic dose) in females (oral): 21 mg/kg/21 days.

LD50 in rats (oral): 960 mg/kg

Markus Falkenstätter

Markus Falkenstätter
Author

Markus Falkenstätter ist Autor zu pharmazeutischen Themen in der Medizin-Redaktion von Medikamio. Er befindet sich im letzten Semester seines Pharmaziestudiums an der Universität Wien und liebt das wissenschaftliche Arbeiten im Bereich der Naturwissenschaften.

Mag. pharm Stefanie Lehenauer

Mag. pharm Stefanie Lehenauer
Lector

Stefanie Lehenauer ist seit 2020 freie Autorin bei Medikamio und studierte Pharmazie an der Universität Wien. Sie arbeitet als Apothekerin in Wien und ihre Leidenschaft sind pflanzliche Arzneimittel und deren Wirkung.

Your personal medicine assistent

afgis-Qualitätslogo mit Ablauf Jahr/Monat: Mit einem Klick auf das Logo öffnet sich ein neues Bildschirmfenster mit Informationen über Medikamio GmbH & Co KG und sein/ihr Internet-Angebot: medikamio.com/ This website is certified by Health On the Net Foundation. Click to verify.
Drugs

Search our database for drugs, sorted from A-Z with their effects and ingredients.

Substances

All substances with their common uses, chemical components and medical products which contain them.

Diseases

Causes, symptoms and treatment for the most common diseases and injuries.

The contents shown do not replace the original package insert of the medicinal product, especially with regard to dosage and effect of the individual products. We cannot assume any liability for the correctness of the data, as the data was partly converted automatically. A doctor should always be consulted for diagnoses and other health questions. Further information on this topic can be found here.