Estrogen (estradiol) is a hormone replacement therapy (HRT) used to relieve symptoms of menopause, including hot flashes, night sweats, vaginal dryness, and mood changes. Estradiol is the most potent naturally occurring estrogen and is available in oral tablets, transdermal gels, and combination products with progestogens. HRT is one of the most effective treatments for menopausal vasomotor symptoms and is also used for the prevention of postmenopausal osteoporosis. The decision to use HRT should be made individually, weighing the benefits against the risks, which include an increased risk of breast cancer, blood clots, and stroke.

Quick Facts: Estrogen (Estradiol)

Active Ingredient
Estradiol
Drug Class
Hormone (Estrogen)
ATC Code
G03CA
Common Uses
Menopause, Osteoporosis
Available Forms
Tablet, Gel
Prescription Status
Rx Only

Key Takeaways

  • Estrogen (estradiol) is the most effective treatment for menopausal vasomotor symptoms such as hot flashes and night sweats, and is also used to prevent postmenopausal osteoporosis.
  • Women with an intact uterus must take progestogen alongside estrogen for at least 12 days per cycle to protect against endometrial hyperplasia and cancer.
  • HRT is associated with increased risks of breast cancer, venous thromboembolism, stroke, and ovarian cancer, especially with prolonged use. The lowest effective dose should be used for the shortest duration necessary.
  • Transdermal estrogen (gels, patches) may carry a lower risk of venous thromboembolism than oral formulations because they bypass first-pass hepatic metabolism.
  • Regular medical check-ups, including breast examination and mammography, are essential during HRT use. Treatment should be reviewed at least annually.

What Is Estrogen and What Is It Used For?

Quick Answer: Estrogen (estradiol) is a hormone replacement therapy (HRT) medication used to relieve menopausal symptoms, particularly hot flashes and night sweats, which occur when the body’s natural estrogen levels decline during menopause. It is available as tablets, gels, and in combination products with progestogens.

Estrogen is the primary female sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. During menopause — the natural cessation of menstruation that typically occurs between the ages of 45 and 55 — the ovaries gradually stop producing estrogen. This decline in estrogen levels can cause a range of symptoms that significantly affect quality of life, including vasomotor symptoms (hot flashes and night sweats), urogenital atrophy (vaginal dryness and discomfort), sleep disturbances, mood changes, and accelerated bone loss.

Hormone replacement therapy (HRT) with estradiol replaces the estrogen that the body no longer produces in sufficient quantities. Estradiol is the most potent naturally occurring estrogen and is biologically identical to the hormone produced by the ovaries. It is classified under ATC code G03CA and is available in several formulations, including oral tablets, film-coated tablets, and transdermal gels. Each formulation has distinct pharmacokinetic properties that may influence both efficacy and safety.

The use of HRT should be initiated only when menopausal symptoms significantly interfere with daily life. International guidelines, including those from the International Menopause Society (IMS), the European Menopause and Andropause Society (EMAS), and the National Institute for Health and Care Excellence (NICE), recommend that HRT be used at the lowest effective dose for the shortest duration necessary to achieve treatment goals. The benefits and risks of continued treatment should be reassessed at least annually.

Approved Indications

Estradiol-based HRT is approved for the following indications:

  • Relief of menopausal vasomotor symptoms: Hot flashes (also called hot flushes) and night sweats are the most common reason for prescribing HRT. These symptoms are caused by the effect of declining estrogen on the thermoregulatory center in the hypothalamus. HRT is the most effective treatment, reducing the frequency and severity of hot flashes by approximately 75% according to Cochrane systematic reviews. Symptoms typically improve within 4 weeks of starting treatment.
  • Prevention of postmenopausal osteoporosis: Estrogen plays a critical role in maintaining bone density. Following menopause, the rate of bone loss accelerates significantly, increasing the risk of osteoporotic fractures, particularly of the hip, spine, and wrist. HRT has been shown to reduce the risk of all osteoporotic fractures, including hip fractures, and is recommended as a treatment option for women who are at high risk of fractures and for whom other osteoporosis treatments are not suitable or are contraindicated.
  • Premature ovarian insufficiency (POI): Women who experience menopause before the age of 40, whether naturally or as a result of surgery (bilateral oophorectomy), radiation, or chemotherapy, are recommended HRT at least until the average age of natural menopause (approximately 51 years) to reduce the increased risks of cardiovascular disease, osteoporosis, cognitive decline, and urogenital symptoms associated with premature estrogen deficiency.

How Estradiol Works

Estradiol exerts its biological effects by binding to two types of estrogen receptors: estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). These receptors are found throughout the body, including in the reproductive tract, bones, cardiovascular system, brain, and skin. When estradiol binds to these receptors, it activates gene transcription, leading to the production of proteins that mediate the hormone’s physiological effects.

In the context of menopausal symptoms, estradiol acts on the thermoregulatory center in the hypothalamus to stabilize the body’s temperature regulation, which is disrupted by declining estrogen levels. This is the mechanism by which HRT alleviates hot flashes. In bone, estradiol inhibits osteoclast activity (cells that break down bone tissue) and promotes osteoblast function (cells that build new bone), thereby maintaining bone mineral density and reducing fracture risk.

Oral estradiol undergoes significant first-pass metabolism in the liver, where it is converted to estrone (a less potent estrogen) and conjugated metabolites. This hepatic first-pass effect can influence the synthesis of hepatic proteins, including clotting factors, which may contribute to the increased risk of venous thromboembolism observed with oral HRT. Transdermal formulations (gels and patches) deliver estradiol directly into the systemic circulation, bypassing first-pass metabolism. This results in a more physiological estradiol-to-estrone ratio and may carry a lower risk of certain adverse effects, including blood clots and effects on triglyceride levels.

What Should You Know Before Taking Estrogen?

Quick Answer: Do not take estrogen if you have or have had breast cancer, estrogen-dependent cancer, unexplained vaginal bleeding, untreated endometrial hyperplasia, blood clots, liver disease, or porphyria. Discuss your complete medical history and family history with your doctor before starting HRT, including any history of heart disease, stroke, or blood clotting disorders.

Before starting HRT, or before restarting treatment, your doctor will take a thorough medical and family history. A general medical and gynecological examination, including breast examination, may be performed. Once treatment has begun, regular check-ups should take place at least once a year. During these visits, the benefits and risks of continuing treatment will be discussed. You should also perform regular breast self-examinations and attend mammography screening as recommended.

Contraindications

You must not take estrogen (estradiol) in the following situations:

If any of these conditions develop for the first time while you are taking estrogen, stop treatment immediately and contact your doctor.

Warnings and Precautions

Talk to your doctor before starting estrogen treatment if you have or have had any of the following conditions, as they may recur or worsen during treatment. If any of these occur, more frequent medical monitoring will be necessary:

  • Uterine conditions: Including fibroids (myomas), endometriosis, or a history of endometrial hyperplasia. Estrogen stimulates the growth of the uterine lining, and without adequate progestogen opposition, the risk of endometrial hyperplasia and cancer is significantly increased.
  • Risk factors for blood clots: Including obesity (BMI over 30), a family history of blood clots, systemic lupus erythematosus (SLE), or a personal history of conditions requiring anticoagulation therapy. Oral HRT increases the risk of venous thromboembolism by 1.3 to 3 times compared to non-users, particularly during the first year of treatment.
  • Family history of breast cancer: If a first-degree relative (mother, sister, daughter) has had breast cancer or other estrogen-dependent cancer, the risk-benefit assessment should be carefully considered with your doctor.
  • High blood pressure: Blood pressure should be monitored regularly during HRT, as some women may experience an increase in blood pressure.
  • Liver disease: Including liver adenoma (a benign liver tumor). Liver function should be monitored if any abnormalities are detected.
  • Diabetes: Blood glucose levels may be affected during HRT, and monitoring may be needed.
  • Gallstone disease: Oral estrogen may increase the risk of gallbladder disease.
  • Migraine or severe headaches: The onset or worsening of migraine-like headaches should prompt a medical review.
  • Epilepsy, asthma, or otosclerosis: These conditions may be exacerbated by HRT.
  • High triglycerides: Oral estrogen may increase triglyceride levels, which in rare cases can lead to pancreatitis.
  • Fluid retention: Due to heart or kidney disease. Estrogen may cause fluid retention, and these conditions should be monitored closely.
  • Hereditary or acquired angioedema: Estrogen may induce or exacerbate symptoms of angioedema.
Stop Treatment and Seek Immediate Medical Attention If:

You develop jaundice (yellowing of the skin or eyes), a significant rise in blood pressure, new migraine-like headaches, signs of a blood clot (painful swelling and redness of the legs, sudden chest pain, difficulty breathing), symptoms of angioedema (swelling of the face, tongue, or throat with difficulty swallowing or breathing), or if you become pregnant.

Pregnancy and Breastfeeding

Estrogen-based HRT is intended for postmenopausal women and is not indicated for use during pregnancy or breastfeeding. If you become pregnant while taking estrogen, stop treatment immediately and contact your doctor. If it is less than 12 months since your last menstrual period, or if you are under 50 years of age, you may still need to use contraception, as estrogen HRT is not a contraceptive. Consult your doctor for appropriate advice.

Transdermal Estrogen: Preventing Unintentional Transfer

When using estrogen gel, the active ingredient (estradiol) can be transferred to others through close skin contact, including to partners, children, and pets. To prevent unintentional transfer:

  • Wash your hands with soap and water after applying the gel.
  • Once the gel has dried, cover the application area with clothing.
  • Shower or wash the application area before skin-to-skin contact with others.
  • If a child comes into contact with the application area, wash the child’s skin with soap and water as soon as possible. Children may develop unexpected signs of puberty (such as breast development) from estradiol exposure. In most cases, these symptoms resolve once exposure is stopped. Consult a doctor if you notice any signs or symptoms in a child who may have been exposed.

HRT and Cancer Risk

Endometrial Cancer

Using estrogen-only HRT significantly increases the risk of endometrial hyperplasia and endometrial cancer. Adding a progestogen for at least 12 days per 28-day cycle protects against this increased risk. If your uterus has been removed (hysterectomy), discuss with your doctor whether you can take estrogen alone. Among women aged 50–65 who still have a uterus and are not taking HRT, approximately 5 in 1,000 will be diagnosed with endometrial cancer. For those taking estrogen-only HRT, between 10 and 60 per 1,000 will be diagnosed (5 to 55 extra cases), depending on the dose and duration of use.

Breast Cancer

Evidence shows that both combined estrogen-progestogen HRT and estrogen-only HRT increase the risk of breast cancer. The increased risk depends on how long you use HRT and becomes apparent within 3 years of starting treatment. After stopping HRT, the excess risk decreases over time but may persist for 10 years or more if you have used HRT for more than 5 years.

For women aged 50–54 not taking HRT, approximately 13 to 17 per 1,000 will be diagnosed with breast cancer over a 5-year period. For women starting estrogen-only HRT at age 50 for 5 years, 16–17 cases per 1,000 are expected (0–3 extra cases). For combined estrogen-progestogen HRT used for 5 years, 21 cases per 1,000 are expected (4–8 extra cases). Over a 10-year period starting at age 50, estrogen-only HRT is associated with approximately 7 extra cases per 1,000 users, while combined HRT is associated with approximately 21 extra cases per 1,000 users.

It is important to check your breasts regularly and report any changes — such as dimpling, changes in the nipple, or lumps that you can see or feel — to your doctor. Inform the healthcare professional performing your mammography that you are using HRT, as it may increase breast density and make mammographic interpretation more difficult.

Ovarian Cancer

Ovarian cancer is rare — much rarer than breast cancer. The use of estrogen-only or combined estrogen-progestogen HRT has been associated with a slightly increased risk. Among women aged 50–54 not taking HRT, approximately 2 in 2,000 will be diagnosed with ovarian cancer over a 5-year period. For those who have taken HRT for 5 years, there will be approximately 3 cases per 2,000 users (approximately 1 extra case).

HRT and Cardiovascular Risk

Venous Thromboembolism (Blood Clots)

The risk of venous thromboembolism (VTE) — blood clots in the veins of the legs (deep vein thrombosis) or lungs (pulmonary embolism) — is 1.3 to 3 times higher in HRT users than in non-users, particularly during the first year of treatment. Blood clots can be serious: if a clot travels to the lungs, it can cause chest pain, breathlessness, collapse, or even death.

You are more likely to develop VTE if you are significantly overweight (BMI over 30), have had blood clots before, have a family history of blood clots, have a thrombophilic disorder, have systemic lupus erythematosus (SLE), have cancer, or are immobilized for prolonged periods following surgery, injury, or illness. For women in their 50s not taking HRT, 4–7 per 1,000 are expected to develop a VTE over a 5-year period. For those taking combined HRT for over 5 years, 9–12 per 1,000 are expected (5 extra cases). For those taking estrogen-only HRT for over 5 years, 5–8 per 1,000 are expected (1 extra case).

Transdermal estrogen may be associated with a lower risk of VTE compared to oral formulations, although the evidence is not yet conclusive. If you require surgery, tell your surgeon that you are taking HRT, as you may need to stop treatment 4–6 weeks before the procedure to reduce the risk of blood clots.

Heart Disease

There is no evidence that HRT prevents heart attacks. For women over 60 years of age taking combined estrogen-progestogen HRT, the risk of developing heart disease is slightly higher than for those not taking HRT. For women who have had a hysterectomy and are taking estrogen-only HRT, there is no increased risk of heart disease.

Stroke

The risk of stroke is approximately 1.5 times higher in HRT users compared to non-users. This risk is age-dependent and increases with advancing age. For women in their 50s not taking HRT, approximately 8 per 1,000 are expected to have a stroke over a 5-year period. For those taking HRT for over 5 years, approximately 11 per 1,000 are expected (3 extra cases).

HRT and Cognitive Function

HRT does not prevent memory loss or cognitive decline. There is some evidence that the risk of dementia may be slightly higher in women who begin HRT after the age of 65. Consult your doctor for individualized advice regarding the timing of HRT initiation.

How Does Estrogen Interact with Other Drugs?

Quick Answer: Several medications can reduce the effectiveness of estrogen, including certain anti-epileptic drugs (phenobarbital, phenytoin, carbamazepine), antibiotics for tuberculosis (rifampicin), some HIV medications, and the herbal supplement St. John’s Wort. Estrogen may also affect the efficacy of lamotrigine (an anti-epileptic) and some hepatitis C treatments. Always tell your doctor about all medications you are taking.

Certain medications can interfere with estrogen therapy, either by reducing its effectiveness (which may lead to breakthrough bleeding) or by being affected by estrogen itself. It is essential to inform your doctor or pharmacist about all medications you are currently taking, including prescription drugs, over-the-counter medicines, and herbal supplements.

Known Drug Interactions with Estrogen
Interacting Drug Drug Class Effect on Estrogen Clinical Significance
Phenobarbital, Phenytoin, Carbamazepine Anti-epileptics Decreased estrogen levels (enzyme inducers) May reduce HRT effectiveness; dose adjustment may be needed
Rifampicin, Rifabutin Anti-tuberculosis agents Significantly decreased estrogen levels Strongly reduces HRT effectiveness; alternative formulations may be considered
Nevirapine, Efavirenz, Ritonavir, Nelfinavir HIV antiretrovirals Decreased estrogen levels May reduce HRT effectiveness; consult specialist
St. John’s Wort (Hypericum perforatum) Herbal supplement Decreased estrogen levels (enzyme inducer) Avoid concurrent use; may cause breakthrough bleeding
Lamotrigine Anti-epileptic Estrogen may decrease lamotrigine levels May increase seizure frequency; dose monitoring required
Ombitasvir/Paritaprevir/Ritonavir, Glekaprevir/Pibrentasvir Hepatitis C antivirals May cause elevated liver enzymes (ALT) Liver function monitoring required; interaction may differ with estradiol vs ethinylestradiol

Enzyme Inducers and Estrogen Metabolism

Many of the drug interactions listed above occur because certain medications act as enzyme inducers — they accelerate the hepatic metabolism of estradiol by inducing cytochrome P450 enzymes (particularly CYP3A4). This results in lower circulating levels of estradiol, which may reduce the therapeutic effect of HRT and cause breakthrough bleeding or spotting. If you are taking any enzyme-inducing medication, your doctor may need to adjust the estrogen dose or consider alternative formulations.

Effect on Blood Test Results

If you need to have blood tests, inform the doctor or the person taking the blood sample that you are taking estrogen HRT. Estradiol can affect the results of certain laboratory tests, including thyroid function tests (it may increase thyroxine-binding globulin), coagulation parameters, and levels of certain binding proteins. Your doctor will take this into account when interpreting the results.

What Is the Correct Dosage of Estrogen?

Quick Answer: The usual dose of estradiol is 0.5 mg to 1.5 mg per day, depending on the formulation and individual response. Your doctor will prescribe the lowest effective dose to treat your symptoms for the shortest duration necessary. If you are using estrogen gel, apply it once daily to the lower abdomen or thighs.

Always use estrogen exactly as your doctor has prescribed. Your doctor aims to prescribe the lowest effective dose to treat your symptoms for the shortest possible time. Do not change the dose without consulting your doctor first. If you feel the dose is too strong or not strong enough, talk to your doctor.

Oral Estradiol (Tablets)

Adults (Postmenopausal Women)

  • Starting dose: Typically 1 mg estradiol once daily.
  • Dose range: 0.5 mg to 2 mg daily, adjusted based on symptom response.
  • Low-dose option: 0.5 mg daily may be sufficient for some women, particularly for bone protection or if side effects occur at higher doses.
  • Tablets should be taken at approximately the same time each day, with or without food.

Transdermal Estradiol (Gel)

Adults (Postmenopausal Women)

  • Usual dose: 0.5 mg to 1.5 mg estradiol per day, applied as gel.
  • Gel sachets: Available as 0.5 g sachets (containing 0.5 mg estradiol) or 1 g sachets (containing 1 mg estradiol).
  • For a daily dose of 0.5 mg: Use one 0.5 g sachet.
  • For a daily dose of 1 mg: Use one 1 g sachet or two 0.5 g sachets.
  • For a daily dose of 1.5 mg: Use three 0.5 g sachets, or one 0.5 g and one 1 g sachet.

How to Apply Estrogen Gel

Follow these steps when applying estrogen gel:

  1. Apply the gel once daily to clean, dry skin on the lower abdomen or thighs.
  2. Spread the gel over an area approximately 1–2 times the size of your hand.
  3. Allow the gel to dry for a few minutes before covering with clothing.
  4. Wash your hands thoroughly after application. Avoid getting gel in your eyes, as it may cause irritation.
  5. Do not wash the application area for at least one hour.
  6. Do not apply the gel to the breasts, face, or irritated skin.
  7. Alternate the application site (left and right sides) each day.
  8. Do not allow others to touch the application area until the gel has completely dried. Cover the area with clothing if necessary.

Progestogen Supplementation

If you still have your uterus, your doctor will normally also prescribe a progestogen medication to take for 12–14 days during each monthly cycle. After each course of progestogen, you will usually experience a withdrawal bleed similar to a menstrual period. This combination protects the uterine lining from the stimulatory effects of estrogen and reduces the risk of endometrial hyperplasia and cancer.

When to Start Treatment

  • If you have never used HRT before, you can start treatment immediately.
  • If you are switching from a continuous combined HRT (one that does not cause monthly bleeds), you can start immediately.
  • If you are switching from a sequential HRT (one that causes monthly bleeds), wait until your current withdrawal bleed has finished before starting.

Missed Dose

If you forget to apply or take your estrogen dose:

  • If you are less than 12 hours late, apply or take the missed dose as soon as you remember.
  • If you are more than 12 hours late, skip the missed dose entirely and take the next dose at the usual time.
  • Do not take a double dose to make up for a missed one.
  • Forgetting doses may increase the likelihood of breakthrough bleeding or spotting.

Overdose

If you have used too much estrogen, or if a child has accidentally ingested the medication, contact your doctor or poison control center immediately. Symptoms of overdose may include nausea, vomiting, bloating, breast tenderness, irritability, and withdrawal bleeding. Overdose through transdermal application (gel on the skin) is unlikely. Treatment consists of washing off the gel and managing symptoms as needed. Symptoms typically resolve when treatment is stopped or the dose is reduced.

Before Surgery

If you are scheduled for surgery, tell the surgeon that you are taking estrogen HRT. You may need to stop treatment 4–6 weeks before the procedure to reduce the risk of blood clots (see the warnings section on venous thromboembolism). Ask your doctor when you can restart estrogen after the operation.

What Are the Side Effects of Estrogen?

Quick Answer: Common side effects of estrogen HRT include breast tenderness, headache, nausea, bloating, skin itching or rash, weight changes, mood changes (depression, nervousness), and hot flashes. Breakthrough bleeding or spotting may occur during the first months of treatment and usually resolves on its own. Seek immediate medical attention if you develop signs of blood clots, jaundice, severe headaches, or allergic reactions.

Like all medicines, estrogen (estradiol) can cause side effects, although not everybody gets them. During the first few months of treatment, breakthrough bleeding, spotting, and breast tenderness or enlargement may occur. These are usually temporary and typically resolve with continued use.

The following conditions are more common in women taking HRT than in those who do not: breast cancer, endometrial hyperplasia or cancer, ovarian cancer, venous thromboembolism, heart disease, stroke, and possible memory loss if HRT is started after age 65. See the detailed information in the “What Should You Know Before Taking Estrogen?” section above.

Common

Affects up to 1 in 10 patients

  • Skin itching, rash, increased sweating
  • Swollen feet and lower legs (edema)
  • Breast tenderness or pain
  • Weight gain or weight loss
  • Headache, dizziness
  • Abdominal pain, nausea, bloating
  • Breakthrough bleeding or spotting, menstrual irregularities
  • Depression, nervousness, listlessness
  • Hot flashes

Uncommon

Affects up to 1 in 100 patients

  • Changes in sex drive and mood, anxiety, insomnia, apathy, emotional instability, difficulty concentrating
  • Migraine, tremors, visual disturbances, dry eyes
  • High blood pressure, superficial phlebitis, purpura
  • Shortness of breath, rhinitis
  • Benign breast or uterine tumors
  • Increased appetite, elevated cholesterol levels
  • Rapid heartbeat (palpitations)
  • Constipation, indigestion, diarrhea
  • Acne, hair loss, dry skin, nail problems, excessive hair growth, urticaria (hives), erythema nodosum
  • Joint problems, muscle cramps
  • Increased urinary frequency, urinary urgency, loss of bladder control, urinary tract infections
  • Abnormal endometrial growth, uterine discomfort
  • Fatigue, weakness, fever, flu-like symptoms, general malaise
  • Allergic reactions (hypersensitivity)

Rare

Affects up to 1 in 1,000 patients

  • Venous thromboembolism (blood clots in legs or lungs)
  • Liver and gallbladder effects
  • Contact lens intolerance
  • Menstrual cramps (dysmenorrhea)
  • Premenstrual-like syndrome

Reported After Marketing (Frequency Unknown)

Cannot be estimated from available data

  • Uterine fibroids (benign tumors of the uterus)
  • Hereditary angioedema (painful swelling of the skin, mucous membranes, or airways)
  • Cerebrovascular disturbances
  • Liver disease causing jaundice
  • Contact dermatitis, eczema
  • Chloasma (dark skin patches, especially on face and neck)
  • Erythema multiforme
  • Vascular purpura
  • Gallbladder disease
  • Dementia (if HRT started after age 65)

Irregular Bleeding During HRT

If your doctor has prescribed progestogen tablets alongside estrogen, you will usually have a monthly withdrawal bleed. However, if you experience unexpected or irregular bleeding beyond this, particularly if it continues for more than 6 months, starts after you have been taking estrogen for 6 months, or persists after you stop taking estrogen, contact your doctor promptly for investigation.

About Skin Discoloration (Chloasma)

Women who are prone to skin discoloration (chloasma — brownish patches, particularly on the face) should minimize their exposure to sun and ultraviolet radiation while using estrogen. Wearing sunscreen and protective clothing can help reduce the risk of this cosmetic side effect.

How Should You Store Estrogen?

Quick Answer: Store estrogen at or below 25°C (77°F). Keep out of the reach and sight of children. Do not use after the expiry date printed on the packaging.

  • Temperature: Store at or below 25°C (77°F). Do not freeze.
  • Packaging: Keep in the original packaging. For gel sachets, use each sachet immediately after opening.
  • Expiry: Do not use after the expiry date (EXP) printed on the carton and sachets. The expiry date refers to the last day of the stated month.
  • Children: Keep out of the sight and reach of children. Accidental exposure to estrogen gel can cause signs of premature puberty in children.
  • Disposal: Do not dispose of medications down the drain or in household waste. Ask your pharmacist for information on how to properly dispose of unused medications. These measures help protect the environment.

What Does Estrogen Contain?

Quick Answer: The active ingredient is estradiol. Gel formulations typically contain 0.5 mg or 1.0 mg of estradiol per sachet. Tablet formulations contain estradiol in various strengths. Inactive ingredients vary by formulation and manufacturer.

Active Ingredient

Estradiol (also known as 17β-estradiol or oestradiol) is the active pharmaceutical ingredient. It is the most potent naturally occurring estrogen and is structurally identical to the estradiol produced by the human ovaries. In oral formulations, estradiol is typically present as estradiol hemihydrate or estradiol valerate. In gel formulations, micronized estradiol is suspended in an alcohol-based gel vehicle for transdermal absorption.

Inactive Ingredients (Excipients)

Gel Formulation (e.g., Divigel)

Typical excipients in estradiol gel formulations include:

  • Carbomer 974P (gelling agent)
  • Trolamine (pH adjuster)
  • Propylene glycol (solvent)
  • Ethanol (alcohol — solvent; may cause a burning sensation on damaged skin)
  • Purified water

Tablet Formulations

Excipients in estradiol tablet formulations vary by manufacturer and may include lactose monohydrate, maize starch, hydroxypropyl cellulose, talc, magnesium stearate, and film-coating agents such as hypromellose and macrogol. Always refer to the patient information leaflet supplied with your specific product for the complete list of excipients.

Available Formulations and Brands

Estradiol is available under numerous brand names worldwide, reflecting the wide variety of formulations and combinations:

  • Divigel — Estradiol gel, 0.5 mg and 1 mg sachets (Orion Corporation)
  • Activelle — Estradiol/norethisterone acetate combination tablets
  • Vagidonna — Vaginal estradiol tablets
  • Femasekvens — Sequential estradiol/norethisterone acetate combination
  • Rosal 28 — Estradiol/drospirenone combination tablets
  • Diza, Dizminelle — Estradiol/drospirenone combinations
  • Estradiol SUN — Generic estradiol tablets

Combination products with progestogens are designed for women who still have a uterus, providing both estrogen replacement and endometrial protection in a single preparation. The exact formulation, dosage form, and available strengths may vary between countries.

Frequently Asked Questions About Estrogen

Estrogen (estradiol) is primarily used as hormone replacement therapy (HRT) to relieve symptoms of menopause, such as hot flashes, night sweats, vaginal dryness, sleep disturbances, and mood changes. It replaces the estrogen that the body stops producing when the ovaries cease functioning during menopause. It is also approved for the prevention of postmenopausal osteoporosis in women at high risk of fractures. For women who experience premature menopause (before age 40), HRT is recommended at least until the average age of natural menopause to protect against the long-term health consequences of early estrogen deficiency.

Yes, both estrogen-only and combined estrogen-progestogen HRT are associated with an increased risk of breast cancer. The risk depends on the duration of use and becomes apparent within approximately 3 years. For estrogen-only HRT used for 5 years starting at age 50, there are approximately 0–3 extra cases per 1,000 women. For combined HRT used for 5 years, there are approximately 4–8 extra cases per 1,000 women. The excess risk decreases gradually after stopping HRT but may persist for 10 years or more after long-term use (more than 5 years). Regular breast screening, self-examination, and mammography are strongly recommended during and after HRT use.

If you still have your uterus, yes — you must take progestogen alongside estrogen. Estrogen-only HRT significantly increases the risk of endometrial hyperplasia (excessive thickening of the uterine lining) and endometrial cancer. Adding progestogen for at least 12 days per 28-day cycle protects the endometrium from this stimulatory effect. If you have had a hysterectomy (your uterus has been surgically removed), you may be able to take estrogen alone without progestogen, but you should discuss this with your doctor. Many HRT products are available as combination tablets that contain both estrogen and progestogen in a single preparation for convenience.

The most common side effects of estrogen HRT include breast tenderness or pain, headache, nausea, abdominal bloating, skin itching or rash, weight changes, mood alterations (such as depression and nervousness), hot flashes, and swelling of the feet or lower legs. Breakthrough bleeding and spotting are also common, especially during the first few months of treatment, but typically resolve on their own. If any side effects persist or become bothersome, discuss them with your doctor, who may adjust the dose, change the formulation, or recommend an alternative treatment.

Apply the gel once daily to clean, dry skin on the lower abdomen or thighs. Do not apply to the breasts, face, or irritated or broken skin. Spread the gel over an area about 1–2 times the size of your hand and allow it to dry for a few minutes. Wash your hands thoroughly with soap and water after application. Do not wash the application area for at least one hour. Avoid skin-to-skin contact with others (particularly children) until the gel has completely dried, and cover the area with clothing. Alternate the application side daily. If the gel accidentally comes into contact with another person, wash the exposed skin with soap and water promptly.

Yes, oral estrogen HRT increases the risk of venous thromboembolism (blood clots in the veins, including deep vein thrombosis and pulmonary embolism) by approximately 1.3 to 3 times compared to non-users, with the highest risk during the first year of use. Transdermal formulations (gels and patches) may carry a lower risk of VTE than oral preparations because they bypass hepatic first-pass metabolism and have less impact on clotting factor synthesis. Risk factors for blood clots include obesity, personal or family history of clots, prolonged immobilization, recent surgery, cancer, and thrombophilic disorders. If you have significant risk factors, discuss the benefits and risks of different HRT formulations with your doctor.

References

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  2. National Institute for Health and Care Excellence (NICE). Menopause: diagnosis and management. NICE guideline [NG23]. Updated 2024. https://www.nice.org.uk/guidance/ng23
  3. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019;394(10204):1159-1168. doi:10.1016/S0140-6736(19)31709-X
  4. Boardman HM, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev. 2015;(3):CD002229. doi:10.1002/14651858.CD002229.pub4
  5. European Medicines Agency (EMA). Estradiol – Summary of Product Characteristics. https://www.ema.europa.eu
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About This Article

This article was written and medically reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in clinical pharmacology, gynecology, and endocrinology. All content follows international medical guidelines (WHO, EMA, FDA, NICE, IMS/EMAS) and is based on peer-reviewed research with evidence level 1A.

Medical Review

Content reviewed by board-certified physicians specializing in gynecology, endocrinology, and clinical pharmacology. All claims verified against current international guidelines and peer-reviewed literature.

Editorial Standards

This content follows the GRADE evidence framework. No commercial funding or pharmaceutical sponsorship. Complete editorial independence. Regular updates to reflect the latest evidence and guideline changes.

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