Estradiol

Estrogens
Estrogens
Pregnancy: contraindicated
Not used in pregnancy; it has no role there and is contraindicated.

The main human estrogen, given by mouth, skin or vagina for menopausal symptoms and estrogen deficiency, with a progestogen if the uterus is present.

Updated Nov 1, 2026

Also called: 17β-estradiol, Estradiol valerate, Estradiol hemihydrate

Quick facts

Group: Estrogens
Target: Estrogen receptor α (ERα), a nuclear receptor
Used for: Moderate to severe hot flushes
Key effects: Breast tenderness · Nausea · Headache
Monitor: Need for continued treatment · Blood pressure
ATC: G03CA03

No doses: the clinician sets them by the current guideline.

Mechanism of action

Estrogen receptor α (ERα), a nuclear receptorEstradiol

The figure shows estradiol itself in the ligand-binding domain of human estrogen receptor α.

Target in 3D: Estrogen receptor α (ERα), a nuclear receptor. PDB structure 1ERE (RCSB PDB, public domain). View the structure at RCSB PDB

Estradiol is identical to the main estrogen made by the ovary. It binds estrogen receptors α and β and changes gene expression in the brain, bone, vagina, urinary tract, liver, breast and endometrium. It relieves hot flushes, restores the vaginal epithelium, slows bone resorption and, by negative feedback, lowers the high LH and FSH of menopause. Without a progestogen it stimulates the endometrium.

Estradiol enters target cells and binds estrogen receptors
The receptor-hormone complex switches estrogen-responsive genes
Hot flushes ease, the vaginal epithelium and bone are preserved
LH and FSH fall through negative feedback

Indications

Moderate to severe hot flushes of menopause Menopause and climacteric syndrome →
Vulvovaginal atrophy of menopause (vaginal products preferred when isolated) Genitourinary syndrome of menopause (atrophic vaginitis) →
Prevention of postmenopausal osteoporosis when non-estrogen drugs are unsuitable Osteoporosis →
Hypoestrogenism from hypogonadism or primary ovarian insufficiency Primary ovarian insufficiency →
Palliation of some advanced prostate and breast cancers Prostate cancer →

Adverse effects

Common

Breast tenderness
Nausea, bloating
Headache
Vaginal bleeding or spotting
Leg cramps, fluid retention

Contraindications

Undiagnosed abnormal genital bleeding
Current or past breast cancer, or estrogen-dependent neoplasia
Active or past DVT, pulmonary embolism, stroke or heart attack
Liver impairment or disease
Protein C, protein S or antithrombin deficiency or other thrombophilia
Pregnancy

Key interactions

CYP3A4 inducers (St John's wort, phenobarbital, carbamazepine, rifampicin): Lower estrogen levels and less effect
CYP3A4 inhibitors (some macrolides, azole antifungals, ritonavir, grapefruit juice): Higher estrogen levels and more side effects
Levothyroxine: Higher thyroid-binding globulin; the thyroid dose may need to rise

What is monitored

Need for continued treatment, reviewed periodically
Blood pressure
Breast examination and mammography
Any abnormal vaginal bleeding (endometrial evaluation)
Triglycerides and TSH in women on thyroid hormone

Administration and safety

Oral, transdermal and vaginal forms exist; the route is as ordered and products are not interchanged without an order
Patches are applied to clean, dry skin and the site is rotated
Used at the lowest effective dose for the shortest time
Stopped, when possible, several weeks before surgery with a high risk of thrombosis or during long immobilisation

Pregnancy and breastfeeding

Not used in pregnancy; it has no role there and is contraindicated.

Nursing care

Teach warning signs: leg pain or swelling, chest pain, sudden breathlessness, facial droop or weakness, sudden vision change or severe headache
Teach to report any vaginal bleeding and breast lumps
Encourage stopping smoking, which adds to the risk of clots and stroke
Ask about thyroid medication
Remind that a woman with a uterus also needs a progestogen

Pharmacokinetics

Absorption: By mouth (with first-pass liver metabolism), through the skin as patches or gel, or in the vagina
Distribution: Bound to SHBG and albumin in plasma
Metabolism: In the liver, partly by CYP3A4, with enterohepatic recirculation
Elimination: As conjugated metabolites in urine

Test yourself

Think of the answer, then tap the question to see it.

Which women taking estradiol also need a progestogen?

Women who still have a uterus, to prevent endometrial hyperplasia and cancer.

Which two cardiovascular risks did estrogen alone raise in the Women's Health Initiative?

Stroke and deep vein thrombosis (it also raised probable dementia in women over 65).

Why is estradiol stopped before major surgery when possible?

It increases the risk of venous thromboembolism, which surgery and immobilisation also raise.

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Connections

← Back to the class: Estrogens

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - ESTRADIOL AND NORETHINDRONE ACETATE tablet (DailyMed (U.S. National Library of Medicine), 2026); Estrogen: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.