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Estradiol

AEMPS

Estrogens — natural and semisynthetic

ATC code: G03CA03

Brand names: Vivelle-Dot, Estrace, Climara, Divigel

Updated · Methodology

Indications

A

Menopausal symptoms

First line

First-line for moderate-to-severe vasomotor menopausal symptoms (hot flashes, night sweats, sleep disturbance) in women under 60 or within 10 years of menopause per NAMS 2022, IMS 2016, BMS 2024. In women with an intact uterus, combine with a progestogen (micronized progesterone or dydrogesterone) is mandatory. In hysterectomized women, estradiol monotherapy. Transdermal preferred over oral in patients with VTE risk, migraine with aura, or hepatic disease.

Sources

  1. Menopause: The 2022 hormone therapy position statement of The North American Menopause Society (2022)
  2. Climacteric: 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy (2016)
  3. Cochrane Database Syst Rev: Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. (2004)

ICD-10: N95.1 · ICD-11: GA30

B

Postmenopausal osteoporosis

Individual decision

In postmenopausal women with osteoporosis or high fracture risk, MHT reduces vertebral and non-vertebral fractures by 30–40 %. Primary prevention is justified only with concurrent vasomotor symptoms or in women under 60 with contraindications to bisphosphonates or denosumab. Endocrine Society 2019 and 2022 do not recommend MHT solely to prevent chronic disease in asymptomatic women.

Sources

  1. Endocrine Society: Postmenopausal Osteoporosis Treatment Guidelines (2019)
  2. JAMA: Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: US Preventive Services Task Force Recommendation Statement. (2022)
  3. JAMA: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. (2002)

ICD-10: M81.0 · ICD-11: FB83.11

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

F

Anti-aging and longevity

Not recommended

Estradiol is the natural female sex hormone. Systemic forms (patches, gels, tablets) are prescribed for menopausal hormone therapy in women with marked vasomotor symptoms or for osteoporosis prevention in early perimenopause (NAMS 2022, NG23). In anti-aging communities, estradiol is promoted as an anti-aging agent for skin, libido, and general rejuvenation. The Women's Health Initiative (JAMA 2002) showed that hormone replacement therapy in healthy postmenopausal women increases risk of breast cancer, ischemic stroke, and thromboembolism, not justifying anti-aging use. The drug has serious risks: increased venous thromboembolism (especially in smokers and obesity), breast cancer on long-term use (over 5 years), gallbladder disease, and endometrial cancer when used without a progestogen in women with a uterus. If estradiol was prescribed for anti-aging without confirmed indications, consider seeking a second opinion.

Sources

  1. JAMA: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. (2002)
  2. JAMA: Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: US Preventive Services Task Force Recommendation Statement. (2022)
  3. Menopause: The 2022 hormone therapy position statement of The North American Menopause Society (2022)
F

Primary cardiovascular prevention in individuals without established CVD

Not recommended

Per 2022, /, and NAMS 2022, MHT is not recommended for cardiovascular disease or dementia prevention in asymptomatic postmenopausal women. The WHI 2002 trial showed increased ischemic stroke and venous thromboembolism with oral forms. Modern data with transdermal forms are more favorable, but routine use for primary CVD prevention is not justified.

Sources

  1. JAMA: Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: US Preventive Services Task Force Recommendation Statement. (2022)
  2. JAMA: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. (2002)
  3. Menopause: The 2022 hormone therapy position statement of The North American Menopause Society (2022)
  4. New England Journal of Medicine: Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol (2016)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Bio-identical 17β-estradiol — the principal endogenous estrogen of reproductive age. Binds estrogen receptors ERα and ERβ in reproductive tissues, bone, CNS, and cardiovascular system. Reduces vasomotor menopausal symptoms, prevents bone mineral density loss, and supports genitourinary epithelium. Oral tablets, transdermal patches, and gels exist — the transdermal route is preferred in patients with thrombosis risk, migraine, or hepatic disease.

Safety

Contraindications

  • Suspected or confirmed breast cancer
  • Suspected or confirmed hormone-dependent cancer (including endometrial)
  • Undiagnosed vaginal bleeding
  • Active or recent venous thromboembolism
  • Active thrombotic disorders (arterial)
  • Severe hepatic disease
  • Known hypersensitivity
  • Pregnancy and breastfeeding
  • Porphyria

Serious adverse effects

  • Venous thromboembolism (1.5–2× risk with oral forms, minimally increased with transdermal)
  • Ischemic stroke
  • Breast cancer with long-term therapy (from 5 years)
  • Endometrial cancer (only with unopposed estrogen monotherapy in women with a uterus)
  • Cholelithiasis
  • Hypertriglyceridemia with pancreatitis risk

Common adverse effects

  • Breast tenderness
  • Nausea
  • Headache
  • Breakthrough bleeding (especially first months)
  • Mood swings
  • Bloating
  • Local irritation from patch or gel

Pregnancy: can you take Estradiol?

Contraindicated in pregnancy. Reliable contraception is required in reproductive-age patients on MHT.

Breastfeeding: can you take Estradiol?

Contraindicated during breastfeeding — suppresses lactation and transfers into milk.

Maternal half-life
1.8 h
Calculate RIDSafe feeding windowFull profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Oral tablets with or without food at the same time daily. Transdermal patch changed once or twice weekly depending on formulation — on dry, intact lower abdomen or buttock skin, rotating sites daily. Gel applied once daily to dry, intact upper-arm or lower-abdomen skin, leave to air-dry. Avoid breast application.

Monitoring

Baseline and yearly: gynecological exam, mammography, BP, lipid profile, liver enzymes. In women with an intact uterus — monitor menstrual pattern; unusual bleeding warrants pelvic ultrasound; endometrial thickness above 5 mm in a postmenopausal woman warrants hysteroscopy with biopsy. Annual reassessment of MHT necessity weighing symptoms, risk factors, and patient preferences.

Drug–drug interactions

6 pairs found. Sorted from critical to minor.

ModerateBudesonideInhaled corticosteroids (ICS)

Mechanism

Oestradiol raises corticosteroid-binding globulin, increasing the bound budesonide fraction. The free fraction changes minimally. The interaction is clinically minor.

Symptoms

No specific clinical manifestations. On long-term systemic therapy, both drugs' side effects may appear.

Management

No dose adjustment needed. In women on menopausal hormone therapy and oral budesonide, check BP, weight, and lipid profile every 6 months. With systemic budesonide over 3 months, consider switching to inhaled glucocorticoids.

Sources

Pair details →Budesonide →

ModerateCarbamazepineAntiepileptics. Carboxamide derivatives

Mechanism

Carbamazepine is a strong CYP3A4 inducer. Plasma oestradiol falls by 40–60%. On menopausal hormone therapy, menopausal symptoms may return; on combined oral contraceptives, unplanned pregnancy risk arises.

Symptoms

Return of vasomotor symptoms: hot flushes, night sweats, sleep disturbance. On oral contraceptives: breakthrough bleeding, conception risk.

Management

On menopausal hormone therapy, double the oestradiol dose or switch to transdermal forms (patch, gel — minimal hepatic metabolism). For contraception on carbamazepine, combined oral contraceptives are unsuitable — choose a levonorgestrel IUS, copper IUD, or depot medroxyprogesterone acetate.

Sources

Pair details →Carbamazepine →

ModeratePhenobarbitalAntiepileptics. Barbiturates

Mechanism

Phenobarbital is a strong CYP3A4 inducer; it lowers oestradiol levels by 40–60%. On menopausal hormone therapy, menopausal symptoms may return. On combined oral contraceptives, unplanned pregnancy risk arises.

Symptoms

Return of vasomotor symptoms: hot flushes, night sweats, sleep disturbance. On oral contraceptives: breakthrough bleeding, conception risk.

Management

On menopausal hormone therapy, raise the oestradiol dose or switch to transdermal forms. For contraception on phenobarbital, combined oral contraceptives are unsuitable — choose a levonorgestrel IUS, copper IUD, or depot medroxyprogesterone acetate. In young women with epilepsy, consider switching phenobarbital to levetiracetam or lamotrigine (no CYP3A4 induction).

Sources

Pair details →Phenobarbital →

MinorAmoxicillinPenicillins with extended spectrum

Mechanism

Same as the ethinylestradiol pair: meta-analyses did not confirm clinically significant reductions in hormone therapy efficacy with broad-spectrum antibiotics.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

For short amoxicillin courses (5–10 days) in women on menopausal hormone therapy, no adjustment needed. Vasomotor symptom monitoring follows the usual schedule.

Sources

Pair details →Amoxicillin →

MinorAzithromycinMacrolides

Mechanism

Azithromycin has minimal effect on CYP3A4 and does not affect hepatic oestradiol metabolism. No clinically significant reduction in menopausal hormone therapy efficacy has been reported.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. In women on menopausal hormone therapy, azithromycin remains an antibiotic of choice for respiratory infections.

Sources

Pair details →Azithromycin →

MinorDoxycyclineTetracyclines

Mechanism

Doxycycline does not induce CYP3A4 and does not affect oestradiol metabolism. No clinically significant reduction in menopausal hormone therapy efficacy has been reported.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. In women on menopausal hormone therapy, doxycycline is used without special precautions for infections requiring it.

Sources

Pair details →Doxycycline →

Label mentions42 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • anticonceptivos hormonalesclass named in the label
    «Se ha demostrado que los anticonceptivos hormonales que contienen estrógenos disminuyen significativamente las concentraciones plasmáticas de lamotrigina cuando se administran conjuntamente debido a…»

    AEMPS, section 4.5 · Open on CIMA

  • antidiabéticosclass named in the label
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: En casos concretos pueden variar los requerimientos de los antidiabéticos orales o la insulina debido a los efectos sobre la…»

    AEMPS, section 4.5 · Open on CIMA

  • antidiabéticos oralesclass named in the label
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: En casos concretos pueden variar los requerimientos de los antidiabéticos orales o la insulina debido a los efectos sobre la…»

    AEMPS, section 4.5 · Open on CIMA

  • antiepilépticosclass named in the label
    «El metabolismo de los estrógenos y progestágenos puede estar aumentado con el uso concomitante de sustancias que se sabe que inducen los enzimas metabolizadores de fármacos, específicamente los…»

    AEMPS, section 4.5 · Open on CIMA

  • antifúngicos azólicosclass named in the label
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • barbitúricosclass named in the label
    «El metabolismo de los estrógenos y progestágenos puede estar aumentado con el uso concomitante de sustancias que se sabe que inducen los enzimas metabolizadores de fármacos, específicamente los…»

    AEMPS, section 4.5 · Open on CIMA

  • Carbamazepine
    «El metabolismo de los estrógenos y progestágenos puede estar aumentado con el uso concomitante de sustancias que se sabe que inducen los enzimas metabolizadores de fármacos, específicamente los…»

    AEMPS, section 4.5 · Open on CIMA

  • Clarithromycin
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • corticosteroidsclass named in the label
    «D. Drug-Laboratory Test Interactions: 3. Other binding proteins may be elevated in serum, i.e., corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total…»

    FDA, section 7 · Open on DailyMed

  • Diltiazem
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • Efavirenz
    «El metabolismo de los estrógenos y progestágenos puede estar aumentado con el uso concomitante de sustancias que se sabe que inducen los enzimas metabolizadores de fármacos, específicamente los…»

    AEMPS, section 4.5 · Open on CIMA

  • Erythromycin
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • Fluconazole
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • Insulin
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: En casos concretos pueden variar los requerimientos de los antidiabéticos orales o la insulina debido a los efectos sobre la…»

    AEMPS, section 4.5 · Open on CIMA

  • insulinaclass named in the label
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: En casos concretos pueden variar los requerimientos de los antidiabéticos orales o la insulina debido a los efectos sobre la…»

    AEMPS, section 4.5 · Open on CIMA

  • Itraconazole
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • Ketoconazole
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • Lamotrigine
    «Se ha demostrado que los anticonceptivos hormonales que contienen estrógenos disminuyen significativamente las concentraciones plasmáticas de lamotrigina cuando se administran conjuntamente debido a…»

    AEMPS, section 4.5 · Open on CIMA

  • macrólidosclass named in the label
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • Paracetamol
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Las sustancias que sufren una conjugación sustancial (p. ej.: paracetamol) pueden aumentar la biodisponibilidad del estradiol…»

    AEMPS, section 4.5 · Open on CIMA

  • Phenytoin
    «El metabolismo de los estrógenos y progestágenos puede estar aumentado con el uso concomitante de sustancias que se sabe que inducen los enzimas metabolizadores de fármacos, específicamente los…»

    AEMPS, section 4.5 · Open on CIMA

  • Rifabutin
    «El metabolismo de los estrógenos y progestágenos puede estar aumentado con el uso concomitante de sustancias que se sabe que inducen los enzimas metabolizadores de fármacos, específicamente los…»

    AEMPS, section 4.5 · Open on CIMA

  • Rifampicin
    «El metabolismo de los estrógenos y progestágenos puede estar aumentado con el uso concomitante de sustancias que se sabe que inducen los enzimas metabolizadores de fármacos, específicamente los…»

    AEMPS, section 4.5 · Open on CIMA

  • Topiramate
    «El metabolismo de los estrógenos y progestágenos puede estar aumentado con el uso concomitante de sustancias que se sabe que inducen los enzimas metabolizadores de fármacos, específicamente los…»

    AEMPS, section 4.5 · Open on CIMA

  • Verapamil
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

  • Voriconazole
    «Sustancias con efectos variables en el aclaramiento de hormonas sexuales: Los inhibidores potentes y moderados del CYP3A4, tales como los antifúngicos azólicos (p. ej., fluconazol, itraconazol…»

    AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

  • Amoxicillin
    «Effects on Laboratory Tests: Following administration of ampicillin or amoxicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol-glucuronide…»

    FDA, section 7 · Open on DailyMed

  • Atorvastatin
    «Anticonceptivos orales: La administración conjunta de atorvastatina con anticonceptivos orales produjo un aumento de las concentraciones plasmáticas de noretindrona y etinil estradiol.»

    AEMPS, section 4.5 · Open on CIMA

  • Cefditoren pivoxil
    «etinil estradiol. Cefditoreno pivoxilo puede tomarse simultáneamente en combinación con»

    AEMPS, section 4.5 · Open on CIMA

  • Efavirenz
    «Established and Other Potentially Significant Drug Interactions: Hormonal contraceptives: Oral Ethinyl estradiol/ Norgestimate Implant Etonogestrel ↓ active metabolites of Norgestimate * ↓…»

    FDA, section 7 · Open on DailyMed

  • Etoricoxib
    «El efecto de etoricoxib sobre la farmacocinética de otros fármacos: Terapia hormonal sustitutiva (THS): la administración de etoricoxib 120 mg con terapia hormonal sustitutiva que contenía estrógenos…»

    AEMPS, section 4.5 · Open on CIMA

  • Everolimus
    «Agentes a los que everolimus puede alterar su concentración plasmática: 45% y un 64% respectivamente. Sin embargo, los correspondientes niveles de estradiol en el estado estacionario (4 semanas) no…»

    AEMPS, section 4.5 · Open on CIMA

  • Fesoterodine
    «Oral Contraceptives: In the presence of fesoterodine, there are no clinically significant changes in the plasma concentrations of combined oral contraceptives containing ethinyl estradiol and…»

    FDA, section 7 · Open on DailyMed

  • Fluconazole
    «Anticonceptivos orales: Se han realizado dos estudios farmacocinéticos con anticonceptivos orales combinados y fluconazol a dosis múltiples. Fluconazol a dosis de 50 mg no produjo efectos relevantes…»

    AEMPS, section 4.5 · Open on CIMA

  • Isotretinoin
    «Oral Contraceptives: It is not known if there is an interaction between Isotretinoin Capsules with oral contraceptives that do not contain norethindrone and ethinyl estradiol.»

    FDA, section 7 · Open on DailyMed

  • Lamotrigine
    «En un estudio con 16 voluntarias, no se produjo ningún efecto en la farmacocinética del etinilestradiol de la píldora anticonceptiva oral en combinación con una dosis de 300 mg de lamotrigina en…»

    AEMPS, section 4.5 · Open on CIMA

  • Montelukast
    «Montelukast puede administrarse junto con otros tratamientos utilizados sistemáticamente en la profilaxis y el tratamiento crónico del asma. En estudios de interacciones farmacológicas, la dosis…»

    AEMPS, section 4.5 · Open on CIMA

  • Nicotine
    «DESCRIPCIÓN DEL EFECTO: Estradiol (anticonceptivos orales)»

    AEMPS, section 4.5 · Open on CIMA

  • Phenobarbital
    «Drug Interactions: Estradiol, Estrone, Progesterone, and other Steroidal Hormones . Pretreatment with or concurrent administration of phenobarbital may decrease the effect of estradiol by increasing…»

    FDA, section 7 · Open on DailyMed

  • Tolterodine
    «Other Interactions: No clinically relevant interactions have been observed when tolterodine was co-administered with warfarin, with a combined oral contraceptive drug containing ethinyl estradiol and…»

    FDA, section 7 · Open on DailyMed

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Frequently asked

What is Estradiol used for?

Estradiol is evaluated for the following indications with varying evidence strength: Menopausal symptoms (evidence tier A), Postmenopausal osteoporosis (evidence tier B), Primary cardiovascular prevention in individuals without established CVD (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Estradiol?

Common side effects of Estradiol (≥ 1 in 100): Breast tenderness, Nausea, Headache, Breakthrough bleeding (especially first months), Mood swings, Bloating. See the Safety section for uncommon and serious reactions.

Is Estradiol safe during pregnancy?

Contraindicated in pregnancy. Reliable contraception is required in reproductive-age patients on MHT.

Is Estradiol compatible with breastfeeding?

Contraindicated during breastfeeding — suppresses lactation and transfers into milk.

Who should not take Estradiol?

Estradiol is contraindicated in: Suspected or confirmed breast cancer; Suspected or confirmed hormone-dependent cancer (including endometrial); Undiagnosed vaginal bleeding; Active or recent venous thromboembolism; Active thrombotic disorders (arterial). Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

Other drugs in this group

Estradiol + Nomegestrol acetate, Estradiol valerate + Dienogest, Ethinylestradiol, Ethinylestradiol + Desogestrel, Ethinylestradiol + Gestodene, Levonorgestrel, Progesterone, micronized, Cyproterone acetate