Estradiol Vaginal

Reviewed on 6/6/2022

What Is Estradiol Vaginal and How Does It Work?

Estradiol vaginal is a prescription medicine used to treat the symptoms of vaginal dryness, burning, and irritation after Menopause (Menopausal Vasomotor Symptoms, Menopausal Vulvar, and Atrophic Vaginitis).

What Are Dosages of Estradiol Vaginal?

Adult dosage

Vaginal cream

  • 0.1mg/g (0.01%) (Estrace Vaginal)

Vaginal insert

  • 4mcg (Imvexxy)
  • 10mcg (Imvexxy, Vagifem, Yuvafem)

Vaginal ring

  • 2mg/ring (releases ~7.5mcg/24hr) (Estring)
  • 12.4mg/ring (releases 0.05mg/24hr for 3 months) (Femring)
  • 24.8mg/ring (releases 0.1mg/24hr for 3 months) (Femring)

Menopausal Vasomotor Symptoms

Adult dosage


  • 1 ring intravaginally for 90 days; replace with a new ring at 90 days if continuing therapy
  • Initiate with the lowest effective dose and the shortest duration consistent with treatment goals
  • Initial: 0.05 mg/day; dosage adjustment should be guided by the clinical response

Menopausal Vulvar and Vaginal Atrophy

Adult dosage

Estrace Vaginal

  • Initial: 2-4 g (marked on the applicator) intravaginally every day for 1-2 weeks, then gradually reduced to 50% of the initial dosage for a similar period
  • Maintenance: 1 g intravaginally 1-3 times/week may be used after restoration of the vaginal mucosa has been achieved


  • 1 ring (2 mg) inserted intravaginally for 90 days; replace with a new ring at 90 days if continuing therapy
  • Attempts to taper or discontinue the medication should be made at 3-6 month intervals


  • 1 ring intravaginally for 90 days; replace with a new ring at 90 days if continuing therapy
  • Initiate with the lowest effective dose and the shortest duration consistent with treatment goals
  • Initial: 0.05 mg/day; dosage adjustment should be guided by the clinical response

Vagifem, Yuvafem

  • Administer intravaginally using the supplied applicator
  • Insert one 10 mcg-insert vaginally every day for 2 weeks; followed by one 10 mcg-insert twice-weekly (eg, Tuesday and Friday)
  • Generally, women should be started with 10 mcg/day


Adult dosage


  • Administer 1 insert intravaginally every day at the approximately same time for 2 weeks, followed by 1 insert twice weekly, every 3-4 days (e.g., Monday and Thursday)
  • Generally, women should start at 4 mcg; dosage adjustment based on clinical response

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”


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What Are Side Effects Associated with Using Estradiol Vaginal?

Common side effects of the Estradiol vaginal include:

  • nausea,
  • vomiting,
  • bloating,
  • stomach cramps,
  • headache,
  • swelling in the hands or feet,
  • weight gain,
  • breast pain,
  • vaginal itching or discharge,
  • changes in the menstrual periods, and
  • breakthrough bleeding.

Serious side effects of the Estradiol vaginal include:

  • fever with nausea,
  • vomiting,
  • diarrhea,
  • muscle pain,
  • dizziness,
  • fainting,
  • sunburn-like skin rash,
  • chest pain or pressure,
  • pain spreading to the jaw or shoulder,
  • nausea,
  • sweating,
  • sudden numbness or weakness (especially on one side of the body),
  • sudden severe headache,
  • slurred speech,
  • problems with vision or balance,
  • sudden vision loss,
  • stabbing chest pain,
  • feeling short of breath,
  • coughing up blood,
  • pain or warmth in one or both legs,
  • swelling or tenderness in the stomach,
  • yellowing of the skin or eyes (jaundice),
  • memory problems,
  • confusion,
  • unusual behavior,
  • unusual vaginal bleeding,
  • pelvic pain,
  • lump in the breast,
  • constipation,
  • increased thirst or urination,
  • muscle weakness,
  • bone pain, and
  • lack of energy.

Rare side effects of the Estradiol vaginal include:

  • none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Estradiol Vaginal?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Estradiol vaginal has severe interactions with no other drugs.
  • Estradiol vaginal has serious interactions with no other drugs.
  • Estradiol vaginal has moderate interactions with at least 52 other drugs.
  • Estradiol vaginal has minor interactions with at least 28 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.


If menopause occurs in a woman younger than ___ years, it is considered to be premature. See Answer

What Are Warnings and Precautions for Estradiol vaginal?


  • Undiagnosed abnormal genital bleeding
  • Known, suspected, or history of breast cancer
  • Known or suspected estrogen-dependent neoplasia
  • Active DVT, PE, or history of these conditions
  • Active arterial thromboembolic disease (eg, stroke, MI), or a history of these conditions
  • Known anaphylactic reaction or angioedema to estrogen
  • Known liver impairment or disease
  • Known protein C, protein S, antithrombin deficiency, or other known thrombophilic disorders
  • Known or suspected pregnancy

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Estradiol vaginal?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Estradiol vaginal?”


  • System absorption occurs with intravaginal administration; consider warnings, precautions, and adverse effects associated with systemic estrogen-alone therapy
  • Increased risk of stroke and DVT reported with estrogen-alone therapy; increased risk of PE, DVT, stroke and MI reported with estrogen plus progestin therapy; discontinue the drug immediately if these conditions occur or are suspected (see Black Box Warnings)
  • The WHI estrogen plus progestin substudy reported a statistically nonsignificant increased risk of ovarian cancer (4 vs 3 cases per 10,000 women-years)
  • Estrogen with or without progesterone may increase the risk of dementia (see Black Box Warnings)
  • Increased risk of gallbladder disease (2- to 4-fold) requiring surgery in postmenopausal women receiving estrogen has been reported
  • Severe hypercalcemia in women with breast cancer and bone metastases is reported with estrogen use; if hypercalcemia occurs, discontinue estrogen and initiate the appropriate treatment to reduce serum calcium level
  • Retinal vascular thrombosis reported; discontinue estrogen pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine; if papilledema or retinal vascular lesions diagnosed, permanently discontinue estrogens
  • Rare occurrences reported of substantial blood pressure increases that were attributed to idiosyncratic reactions to estrogens
  • May cause elevated triglycerides that lead to pancreatitis in women with preexisting hypertriglyceridemia; discontinue estrogens if pancreatitis occurs
  • Estrogens may be poorly metabolized with hepatic impairment; if cholestatic jaundice occurs, discontinued estrogens; exercise caution in any woman with a history of cholestatic jaundice associated with past estrogen use or with pregnancy
  • Estrogen administration leads to increased thyroid-binding globulin (TBG) levels; women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range, however, women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy; monitor thyroid function in these women during treatment to maintain their free thyroid hormone levels in an acceptable range
  • Estrogens may cause some degree of fluid retention; women with conditions that might be influenced by this factor (eg, cardiac or renal impairment) warrant careful observation; monitor any woman with a condition(s) that might predispose her to fluid retention, such as cardiac or renal impairment; discontinue estrogen-alone therapy with evidence of medically concerning fluid retention
  • Malignant transformation of residual endometrial implants has been reported in women treated post-hysterectomy with estrogen-alone therapy; if residual endometriosis post-hysterectomy exists, the addition of progestin should be considered
  • Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema; consider whether the benefits of estrogen therapy outweigh the risks in such women
  • Estrogen therapy may exacerbate asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas; consider whether the benefits of estrogen therapy outweigh the risks in women with these conditions
  • Local abrasion induced by vaginal tablet applicator reported
  • Serum follicle-stimulating hormone (FSH) and estradiol levels are not shown for the management of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause
  • Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity
  • Estrogen-induced hypocalcemia may occur in women with hypoparathyroidism; consider whether the benefits of estrogen therapy outweigh the risks in such women
  • Endometrial cancer
    • Increased risk of endometrial cancer is reported with the use of unopposed estrogen therapy in a woman with a uterus (see Black Box Warnings); clinical surveillance of all women using estrogen-alone or estrogen plus progestogen therapy is important
    • There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose
    • Adding a progestogen to estrogen therapy in postmenopausal women has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer
  • Breast cancer
    • The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the Women’s Health Initiative (WHI) substudy of daily PO conjugated estrogens (CE) (0.625 mg)-alone
    • In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE-alone was not associated with an increased risk of invasive breast cancer (see Black Box Warnings)
    • Drug interactions overview
    • CYP3A4 inducers or inhibitors may affect estrogen drug metabolism
    • CYP3A4 inducers (e.g., St. John's wort [Hypericum perforatum] preparations, phenobarbital, carbamazepine, and rifampin) may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile
    • CYP3A4 inhibitors (e.g., erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, grapefruit juice) may increase plasma concentrations of estrogens and may result in side effects

Pregnancy and Lactation

  • Estrogens should not be used during pregnancy (see Contraindications)
  • There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy
  • Lactation
    • Should not be used during lactation; estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk
    • Detectable amounts of estrogens have been identified in the breast milk of women receiving estrogen therapy
    • Caution should be exercised when estrogen is administered to a nursing woman
    • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from the drug or the underlying maternal condition

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