Estradiol


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Menopausal hormone replacement therapy; Moderate to severe vasomotor symptoms associated with menopause; Menopausal atrophic vaginitis; Hypogonadism-associated oestrogen deficiency; Primary ovarian failure-associated oestrogen deficiency; Castration-associated oestrogen deficiency 1-2 mg/day. Prophylaxis of osteoporosis in postmenopausal women 2 mg/day. Palliative treatment for metastatic breast cancer 10 mg tid. Palliative treatment for advanced prostate cancer 1-2 mg tid. IM Moderate to severe vasomotor symptoms associated with menopause As estradiol cypionate: 1-5 mg every 3-4 weeks. Hypogonadism-associated oestrogen deficiency As estradiol cypionate: 1.5-2 mg/month. Menopausal atrophic vaginitis; Moderate to severe vasomotor symptoms associated with menopause; Hypogonadism-associated oestrogen deficiency; Primary ovarian failure-associated oestrogen deficiency; Castration-associated oestrogen deficiency As estradiol valerate: 10-20 mg every 4 weeks. Palliative treatment for advanced prostate cancer As estradiol valerate: ≥30 mg every 1-2 weeks. Transdermal Menopausal hormone replacement therapy Each patch delivers 0.025-0.1 mg estradiol/24 hours: Apply once or twice weekly. As gel containing 0.5 or 1 mg estradiol/single-dose container: Apply 0.5-1.5 mg once daily. Moderate to severe vasomotor symptoms associated with menopause Each patch delivers 0.025-0.1 mg estradiol/24 hours: Apply once or twice weekly. As gel containing 0.25, 0.5 or 1 mg estradiol/container: Apply 0.5-1.5 mg once daily. As gel in metered dose pump releasing 0.52 or 0.75 mg estradiol/actuation: Apply once daily. As spray releasing 1.53 mg estradiol/actuation: 1-3 sprays once daily. Menopausal atrophic vaginitis Each patch delivers 0.025-0.1 mg estradiol/24 hours: Apply once or twice weekly. As gel in metered dose pump releasing 0.75 mg estradiol/actuation: Apply once daily. Prophylaxis of osteoporosis in postmenopausal women Each patch delivers 0.014-0.1 mg estradiol/24 hours: Apply once or twice weekly. Menopausal atrophic vaginitis; Moderate to severe vasomotor symptoms associated with menopause; Hypogonadism-associated oestrogen deficiency; Primary ovarian failure-associated oestrogen deficiency; Castration-associated oestrogen deficiency Each patch delivers 0.025-0.1 mg mg estradiol/24 hours: Apply once or twice weekly. Vaginal Moderate to severe vasomotor symptoms associated with menopause As vaginal ring releasing 0.05 or 0.1 mg estradiol/24 hours: 1 ring for 90 days. Menopausal atrophic vaginitis As vaginal ring releasing 0.0075, 0.05 or 0.1 mg estradiol/24 hours: 1 ring for 90 days. As vaginal tab containing 0.01 mg estradiol or as vaginal insert containing 0.01 mg or 0.025 mg estradiol: 1 tab or insert/day for 2 weeks then, 1 tab or insert twice weekly. As 0.01% vaginal cream: 2-4 g/day for 1 or 2 weeks, reduce to 1-2 g/day for 1 or 2 weeks, then 1 g 1-3 times/week as maintenance.
Dosage Details
Intramuscular
Advanced prostate cancer
Adult: As palliative treatment: As estradiol valerate: ≥30 mg every 1-2 weeks.

Intramuscular
Castration-associated oestrogen deficiency, Hypogonadism-associated oestrogen deficiency, Menopausal atrophic vaginitis, Moderate to severe vasomotor symptoms associated with menopause, Primary ovarian failure-associated oestrogen deficiency
Adult: As estradiol valerate: 10-20 mg every 4 weeks.

Intramuscular
Hypogonadism-associated oestrogen deficiency
Adult: As estradiol cypionate: 1.5-2 mg monthly.

Intramuscular
Moderate to severe vasomotor symptoms associated with menopause
Adult: As estradiol cypionate: 1-5 mg every 3-4 weeks.

Oral
Castration-associated oestrogen deficiency, Hypogonadism-associated oestrogen deficiency, Menopausal atrophic vaginitis, Menopausal hormone replacement therapy, Moderate to severe vasomotor symptoms associated with menopause, Primary ovarian failure-associated oestrogen deficiency
Adult: 1-2 mg daily continuously (hysterectomised women) or cyclically (non-hysterectomised women).

Oral
Prophylaxis of osteoporosis in postmenopausal women
Adult: 2 mg daily continuously (hysterectomised women) or cyclically (non-hysterectomised women).

Oral
Advanced prostate cancer
Adult: As palliative treatment: 1-2 mg tid.

Oral
Metastatic breast cancer
Adult: As palliative treatment: 10 mg tid for at least 3 months.

Transdermal
Menopausal hormone replacement therapy
Adult: Each patch delivers 0.025-0.1 mg estradiol per 24 hours: Apply once or twice weekly on a clean, dry area of skin of the lower abdomen or upper buttock. As gel containing 0.5 or 1 mg estradiol per single-dose container: Apply 0.5-1.5 mg daily as a thin layer on either the right or left upper thigh. May be used continuously (hysterectomised women) or cyclically (non-hysterectomised women).

Transdermal
Moderate to severe vasomotor symptoms associated with menopause
Adult: Each patch delivers 0.025-0.1 mg estradiol per 24 hours: Apply once or twice weekly on a clean, dry area of skin of the lower abdomen or upper buttock. As gel containing 0.25, 0.5 or 1 mg estradiol per single-dose container: Apply 0.5-1.5 mg once daily as a thin layer on either the right or left upper thigh. As gel in metered dose pump releasing 0.52 or 0.75 mg estradiol per actuation: Apply once daily as a thin layer on either the right or left upper arm. As spray releasing 1.53 mg estradiol per actuation: 1-3 sprays once daily (in the morning) on adjacent, non-overlapping areas on the inner surface of the forearm.

Transdermal
Menopausal atrophic vaginitis
Adult: Each patch delivers 0.025-0.1 mg estradiol per 24 hours: Apply once or twice weekly on a clean, dry area of skin of the lower abdomen or upper buttock. As gel in metered dose pump releasing 0.75 mg estradiol per actuation: Apply once daily as a thin layer over the entire arm on the inside and outside from wrist to shoulder.

Transdermal
Prophylaxis of osteoporosis in postmenopausal women
Adult: Each patch delivers 0.014-0.1 mg estradiol per 24 hours: Apply once or twice weekly on a clean, dry area of skin of the lower abdomen or upper buttock.

Transdermal
Castration-associated oestrogen deficiency, Hypogonadism-associated oestrogen deficiency, Menopausal atrophic vaginitis, Moderate to severe vasomotor symptoms associated with menopause, Primary ovarian failure-associated oestrogen deficiency
Adult: Each patch delivers 0.025-0.1 mg estradiol per 24 hours: Apply once or twice weekly on a clean, dry area of skin of the lower abdomen or upper buttock.

Vaginal
Menopausal atrophic vaginitis
Adult: As vaginal ring releasing 0.0075, 0.05 or 0.1 mg estradiol per 24 hours Place 1 ring into the upper third of the vagina for 90 days. As vaginal tab containing 0.01 mg estradiol: Place 1 tab daily for 2 weeks then, 1 tab twice weekly. As vaginal insert containing 0.01 mg or 0.025 mg estradiol: Place 1 insert daily for 2 weeks then, 1 insert twice weekly. As 0.01% vaginal cream: 2-4 g daily for 1 or 2 weeks, reduce to 1-2 g daily for 1 or 2 weeks, then 1 g 1-3 times weekly as maintenance.

Vaginal
Moderate to severe vasomotor symptoms associated with menopause
Adult: As vaginal ring releasing 0.05 or 0.1 mg estradiol per 24 hours: Place 1 ring into the upper third of the vagina for 90 days.
Administration
May be taken with or without food.
Contraindications
Hypersensitivity. History or current breast cancer (except for certain metastatic breast cancer cases), CV disorders (e.g. MI, stroke, pulmonary embolism, DVT). Oestrogen-dependent tumours (e.g. endometrial cancer). Undiagnosed genital bleeding. Untreated endometrial hyperplasia. Thrombophilic disorders (e.g. protein C, protein S, antithrombin deficiency). Porphyria. Hepatic impairment. Pregnancy and lactation.
Special Precautions
Patient with history of endometrial hyperplasia, cholestatic jaundice; risk factors for CV disorders (e.g. personal or family history, obesity, diabetes mellitus, hypertension, hypercholesterolaemia, SLE, prolonged immobilisation); leiomyoma (uterine fibroids) or endometriosis, coronary artery disease, migraine, epilepsy, asthma, cholelithiasis, hepatic haemangiomas, hypertriglyceridemia, hypoparathyroidism, severe hypocalcaemia, otosclerosis, cardiac impairment, hereditary angioedema; short narrow vagina, uterovaginal prolapse, vaginal infection (vaginal). Patient who underwent surgery. Not intended for prevention of dementia. Renal impairment. Non-hysterectomised women. Smoking.
Adverse Reactions
Significant: Breast, endometrial or ovarian cancers; endometrial hyperplasia, breakthrough bleeding and spotting, CV disorders (e.g. MI, stroke, pulmonary embolism, DVT), retinal vascular thrombosis, dementia, gallbladder disease, hypertension, increased HDL-cholesterol and decreased LDL-cholesterol, increased thyroid binding globulin levels, chloasma; impotence and feminising effects in males (when used as palliative treatment for advanced prostate cancer); UTI, vaginal irritation or infection (vaginal); breast budding or masses in prepubertal females, gynecomastia and breast masses in prepubertal males (due to secondary exposure).
Ear and labyrinth disorders: Otitis media.
Eye disorders: Conjunctivitis.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, dyspepsia, flatulence, abdominal pain, gastroenteritis.
General disorders and administration site conditions: Weakness, lethargy, oedema, pain, flu-like symptoms.
Infections and infestations: Infections (e.g. fungal infections).
Injury, poisoning and procedural complications: Application site reactions (transdermal).
Metabolism and nutrition disorders: Weight fluctuation.
Musculoskeletal and connective tissue disorders: Arthropathy, arthalgia, myalgia, back, neck or limb pain.
Nervous system disorders: Headache, dizziness, hypoaesthesia.
Psychiatric disorders: Nervousness, anxiety, depression, insomnia, libido disorder.
Renal and urinary disorders: Bladder discomfort (vaginal).
Reproductive system and breast disorders: Dysmenorrhoea, metrorrhagia, vaginal discharge, breast tenderness, pain or enlargement; vulvovaginal discomfort, vaginal haemorrhage (vaginal).
Respiratory, thoracic and mediastinal disorders: Cough, sinus congestion, sinusitis, nasopharyngitis, pharyngitis, upper respiratory tract infection, bronchitis, rhinitis, asthma.
Skin and subcutaneous tissue disorders: Rash, erythema, pruritus, hyperhidrosis.
Vascular disorders: Hot flushes.
Potentially Fatal: Anaphylaxis.
IM/Parenteral/PO/Topical/Transdermal/Vag: X
MonitoringParameters
Assess personal and family medical history before and regularly during therapy. Include blood pressure, breast and endometrial examinations including mammography, endometrial sampling and Papanicolaou smear. Also monitor bone density (when used as prophylaxis of osteoporosis); for signs and symptoms of retinal vascular thrombosis, thromboembolic disorders. Periodically evaluate the need to continue treatment.
Overdosage
Symptoms: Nausea, vomiting, bloating, abdominal pain, breast pain or tenderness, withdrawal bleeding. Management: Administer gastric lavage and symptomatic treatment.
Drug Interactions
May cause increased exposure with CYP3A4 inhibitors (e.g. fluconazole, clarithromycin, diltiazem. May cause decreased exposure with CYP3A4 inducers (e.g. phenobarbital, griseofulvin, rifampicin, efavirenz. Decreases absorption of folic acid.
Food Interaction
Avoid alcohol. May cause increased exposure with grapefruit juice. May cause decreased exposure with St. John’s Wort.
Lab Interference
May interfere with results of tests for coagulation factors, lipids, glucose tolerance and binding proteins. Decreases response to metyrapone test.
Action
Description: Estradiol is a synthetic sex hormone similar to endogenous oestrogen. During menopause, estradiol substitutes for oestrogen production and alleviates its symptoms. Estradiol also prevents bone loss following menopause or ovariectomy.
Synonym: oestradiol.
Pharmacokinetics:
Absorption: Well absorbed from the gastrointestinal tract, skin and mucous membranes. Time to peak plasma concentration: 1.5-2 hours (oral).
Distribution: Widely distributed. Enters breast milk. Plasma protein binding: 61% to albumin and approx 37% to sex hormone binding globulin (SHBG).
Metabolism: Metabolised in the liver partially by CYP3A4 enzymes to estrone and estriol. Undergoes enterohepatic recirculation (oral).
Excretion: Mainly via urine as estradiol, estrone, estriol and its glucuronide and sulfate conjugates; faeces as unconjugated metabolites.
Chemical Structure

Chemical Structure Image
Estradiol

Source: National Center for Biotechnology Information. PubChem Database. Estradiol, CID=5757, https://pubchem.ncbi.nlm.nih.gov/compound/Estradiol (accessed on Jan. 22, 2020)

Storage
Store between 20-25°C.
ATC Classification
G03CA03 - estradiol ; Belongs to the class of natural and semisynthetic estrogens used in estrogenic hormone preparations.
References
Anon. Estradiol (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/03/2018.

Anon. Estradiol (Topical). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/03/2018.

Buckingham R (ed). Estradiol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/03/2018.

Climara Patch (Bayer HealthCare Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Delestrogen Injection (Par Pharmaceutical, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Depo-Estradiol Injection (Pharmacia and Upjohn Company LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Elestrin Gel, Metered (Meda Pharmaceuticals). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Estrace Cream (Allergan, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Estrace Tablet (Allergan, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Estradiol Gel (Vertical Pharmaceuticals, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Estring Ring (Pharmacia and Upjohn Company LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Estrogel Gel, Metered (Ascend Therapeutics US, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Evamist Spray (Paddock Laboratories, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Femring Ring (Allergan, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Menostar Patch (Bayer HealthCare Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Vagifem Insert (Novo Nordisk). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/03/2018.

Disclaimer: This information is independently developed by MIMS based on Estradiol from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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