Estradiol Vaginal Suppositories Safety Information

These highlights do not include all the information needed to use estradiol vaginal inserts safely and effectively. Please see full prescribing information for estradiol vaginal inserts.

All estrogen products currently carry an FDA black box warning, which is the most serious warning the FDA requires. The warning alerts patients to increased risks of cancer and heart disease. However, in 2025, the FDA has announced plans to remove this black box warning from prescribing information for all estrogen products. The Menopause Society supports removal of the warning only from vaginal estrogen products, which are low-dose and not absorbed significantly throughout the body. Systemic estrogen like the estrogen pill or patch still comes with potential health risks in certain individuals that should be reviewed in detail with patients.

Estradiol vaginal suppositories are a form of vaginal estrogen. Like all forms of vaginal estrogen, estradiol vaginal suppositories are a prescription medication. They’re FDA-approved to treat moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. When you receive your estradiol vaginal suppositories, you’ll open the box and read an FDA warning that estrogens increase risk of cancer and heart disease. These warnings have only been substantiated with higher-dose oral forms of estrogen. Women's health groups state that these warnings do not apply to vaginal estrogen and have been advocating for updated information that reflects the safety of vaginal estrogen.^[1]

Estradiol vaginal suppositories are prescribed in very small doses and are applied only to the affected tissues. Vaginal estradiol is not shown to carry risk of cancer and heart disease, according to analysis of information from over 161,000 women as part of the very large Women’s Health Initiative Observational Study.^[2] It can even be used by women with a history of breast cancer, provided they have approval from their oncologist.^[3]

At Interlude, we want you to feel safe and educated about your options for sexual wellness. If you are considering vaginal estrogen treatment, our medical team will determine if you are a good candidate. We're available 24/7 to answer any questions you may have - unlimited messaging is included with your treatment.

What do estradiol vaginal inserts treat?

Estradiol vaginal inserts are an estrogen indicated for the treatment of atrophic vaginitis due to menopause.

What are the most important things I need to know about vaginal estrogen?

Using estrogen-alone may increase your chance of getting cancer of the uterus (womb).
Report any unusual vaginal bleeding right away while you are using estradiol vaginal inserts. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia (decline in brain function).
Using estrogen-alone may increase your chances of getting strokes or blood clots.
Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age or older.
Do not use estrogens with progestogens to prevent heart disease, heart attack, strokes or dementia.
Using estrogens with progestogens may increase your chances of getting blood clots, strokes, heart attacks, or breast cancer.
Using estrogens with progestogens may increase your chance of getting dementia, based on a study of women 65 years of age and older
Only one estrogen-alone product and dose have been shown to increase your chances of getting strokes, blood clots, and dementia. Only one estrogen with progestogen product and dose have been shown to increase your chances of getting heart attacks, strokes, breast cancer, blood clots, and dementia.
Because other products and doses have not been studied in the same way, it is not known how the use of estradiol vaginal inserts will affect your chances of these conditions. You and your healthcare provider should talk regularly about whether you still need treatment with estradiol vaginal inserts.

What are estradiol vaginal inserts?

Estradiol vaginal inserts are a prescription medicine that contains estradiol (an estrogen hormone) in a vaginal insert.

What are estradiol vaginal inserts used for?

Estradiol vaginal inserts are used after menopause to:

Treat moderate to severe menopausal changes in and around the vagina
You and your healthcare provider should talk regularly about whether you still need treatment with estradiol vaginal inserts to control these problems.

What are the ingredients in estradiol vaginal inserts?

Each estradiol vaginal insert, 10 mcg contains the following excipients: colloidal silicon dioxide, corn starch, hypromellose, lactose monohydrate, and magnesium stearate. The film coating contains hypromellose and polyethylene glycol.

Who should not take vaginal estradiol?

Do not use vaginal estradiol if you:

have unusual vaginal bleeding. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

Before you use estradiol vaginal inserts, tell your healthcare provider about all of your medical conditions, including if you:

have unusual vaginal bleeding. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how estradiol vaginal inserts works. Estradiol vaginal inserts may also affect how your other medicines work. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get new medicines.

How should I use estradiol vaginal inserts?

Estradiol vaginal inserts are an insert that you place in your vagina with an applicator.

Take the dose recommended by your healthcare provider and talk to him or her about how well that dose is working for you
Estrogens should be used at the lowest dose possible for your treatment and only as long as you need to use this medicine.

You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are using and whether you still need treatment with estradiol vaginal inserts.

What are the possible side effects of estradiol vaginal cream?

Side effects are grouped by how serious they are and how often they happen when you are treated.

Less common but serious side effects include:

heart attack
stroke
blood clots
breast cancer
cancer of the lining of the uterus (womb)
cancer of the ovary
dementia
high and low blood calcium
gallbladder disease
visual abnormalities
high blood pressure
high levels of fat (triglyceride) in your blood
liver problems
changes in your thyroid hormone levels
fluid retention
cancer changes of endometriosis
enlargement of benign tumors of the uterus ("fibroids")
worsening of swelling of face and tongue (angioedema) in women with a history of angioedema

Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:

new breast lumps
unusual vaginal bleeding
changes in vision or speech
sudden new severe headaches
severe pains in your chest or legs with or without shortness of breath, weakness, and fatigue

Common side effects include:

headache
breast pain
irregular vaginal bleeding or spotting
stomach or abdominal cramps, bloating
nausea and vomiting
hair loss
fluid retention
vaginal yeast infection

These are not all the possible side effects of estradiol vaginal inserts. For more information, ask your healthcare provider or pharmacist. Tell your healthcare provider if you have any side effects that bother you or do not go away. You may report side effects to FDA at 1-800-FDA-1088.

References

Pinkerton JV, Santoro N. Why the product labeling for low-dose vaginal estrogen should be changed. Menopause. 2014;21(9):911–916.
Vinogradova Y, Coupland C, Hippisley-Cox J. Breast cancer, endometrial cancer, and cardiovascular events in recipients of low-dose vaginal estrogens. Menopause. 2018;25(1).
Vaginal estrogen use in breast cancer survivors. American Journal of Obstetrics and Gynecology. 2024.

Disclaimer: This information isn’t a substitute for professional medical advice, diagnosis, or treatment. You should never rely upon this article for specific medical advice. If you have any questions or concerns, please talk to your doctor.

Safety Information for Estradiol Vaginal Suppositories (10mcg)