Estradiol vaginal cream side effects and how to avoid them

In this article:

• What is estradiol vaginal cream?
• Common side effects
• Serious side effects
• How soon side effects start
• How long side effects last
• Long-term side effects
• Interactions
• How to avoid side effects
• How to treat side effects

In this article

• What is estradiol vaginal cream?
• Common side effects
• Serious side effects
• How soon side effects start
• How long side effects last
• Long-term side effects
• Interactions
• How to avoid side effects
• How to treat side effects

Estradiol vaginal cream is a topical treatment that is used to relieve some of the vaginal symptoms of menopause, such as dryness, itching, burning, and vaginal atrophy. It can also help with urinary urgency and frequency, and sexual discomfort. Other forms of estradiol vaginal therapy include tablets, inserts, and vaginal rings, but this article will focus primarily on vaginal cream.

It’s common to have concerns about using estrogen-containing medications. But unlike systemic forms of estrogen therapy, such as patches, injections, or pills, estradiol vaginal cream is among the lowest-risk hormone medications. Estradiol vaginal cream side effects tend to be minimal, and long-term estradiol cream side effects, like cancer or heart disease, are rare.

What is estradiol vaginal cream?

Estradiol vaginal cream is an estrogen-containing cream that’s applied locally to the vaginal tissues. Common brand names include Estrace and Premarin cream. Vagifem is another type of topical estrogen treatment, but it’s a vaginal insert and not an estrogen cream.

Its main indication is for the treatment of genitourinary syndrome of menopause (GSM), which is when the vaginal tissues become dry and less elastic due to decreasing estrogen levels during menopause. Symptoms of GSM include vaginal dryness, itching, burning, pain with sex, and increased urinary urgency, frequency, and discomfort.

GSM can be treated with vaginal lubricants and moisturizers. Low-dose vaginal estrogen therapy, like vaginal estrogen cream, is considered an effective and low-risk treatment for GSM, according to both the North American Menopause Society and American College of Obstetricians and Gynecologists.

Estradiol vaginal cream works by delivering estrogen hormones directly to the vaginal mucosa, explains Kecia Gaither, MD, double board-certified in OB-GYN and maternal fetal medicine and director of perinatal and maternal fetal medicine at NYC Health + Hospital. “The result is improved vaginal moisture, thickness, blood flow, and elasticity, relieving symptoms of dryness, itching, burning, and pain during intercourse,” she explains.

It’s important to understand that estradiol vaginal cream isn’t the same as systemic forms of hormone replacement therapy (HRT), like pills, patches, and injections. “Systemic therapy circulates estrogen through the body, affecting multiple organs, while the cream acts locally,” Dr. Gaither says.

The fact that estradiol vaginal cream doesn’t circulate widely throughout the body is why it’s considered a lower-risk medication than other HRT treatments. “Vaginal cream mainly stays local, which means there is very little estrogen absorbed into the bloodstream. Because of that, the risk of serious side effects is generally much lower than with full-body hormone therapy,” explains Eboni January, MD, OB-GYN and author of “Empowered Motherhood: Essential Guide to Thriving During Pregnancy and Beyond.” 

Common side effects of estradiol vaginal cream

Estradiol vaginal cream can cause side effects for some people, although side effects tend to be minimal. According to Dr. Gaither, common side effects of estradiol include vaginal burning, irritation, vaginal discharge or spotting, breast tenderness, and an increased risk of vaginal infections.

According to MedlinePlus, other possible side effects of estradiol vaginal cream include:

• Headaches
• Nausea
• Vomiting
• Diarrhea
• Stomach pain
• Bloating
• Trouble sleeping
• Changes in sex drive
• Hair loss
• Darkening of the facial skin
• Hot flashes or sweating
• Painful urination

Serious side effects of estradiol vaginal cream

In rare cases, estradiol vaginal cream can cause serious side effects. According to MedlinePlus, serious side effects of vaginal estrogen cream may include:

• Bulging eyes
• Severe headaches
• Pain in the stomach that can spread to the back
• Serious nausea or vomiting
• Loss of appetite
• Signs of allergic reactions, like rashes, hives, itching, or shortness of breath
• Chest pain or trouble breathing
• Signs of angioedema, such as swelling of the face, eyes, or tongue
• Swelling of the feet, hands, ankles, or legs
• Fever
• Muscle pain
• Dizziness
• Fainting
• Serious drowsiness

How soon do estradiol vaginal cream side effects start?

If you are going to have side effects from estradiol vaginal cream, you’ll likely notice these soon after starting the medication. “Mild [vaginal] irritation can happen in the first few days,” Dr. January explains. “Breast tenderness or bloating may show up later, if they occur at all.”

How long do estradiol vaginal cream side effects last?

Estradiol vaginal cream side effects don’t typically last long. “These effects typically resolve within days to weeks of continued use and dose adjustment,” Dr. Gaiter says. Dr. January agrees and explains that most side effects will fade once you switch to the maintenance dose, usually just a few times per week. If side effects don’t improve, you can seek medical advice from your healthcare provider about adjusting the dose or type of vaginal estrogen you are using.

What are the long-term side effects of estradiol vaginal cream?

Any estrogen therapy carries a risk of long-term risks, including uterine cancer, breast cancer, and heart disease. But these risks are higher with systemic estrogen treatments, as opposed to localized, topical treatments like estradiol vaginal cream.

The dosage of vaginal estrogen cream is another important consideration. “High-dose vaginal estrogen may additionally increase risks similar to systemic preparations of stroke, clots, and heart attack,” Dr. Gaither explains. “The lowest dose of estrogen in the cream preparation is generally utilized.”

Dr. January says the long-term risk of vaginal estrogen creams is the biggest concern many women have. As she points out, “research has shown that low-dose vaginal estrogen is not linked to higher rates of breast cancer, heart disease, stroke, or blood clots in healthy women.”

What the research says

Several research studies support the concept that estradiol vaginal cream has low long-term risks.

For example, a 2019 study published in Menopause looked at the long-term risks of vaginal estrogen use and health conditions like cardiovascular disease, reproductive cancers, and hip fractures. The researchers studied women who used vaginal estrogen creams but not systemic hormone therapy. After 18 years of follow-up with this group, they found no increased risk of cardiovascular disease, cancers, or hip fractures.

In addition, a 2019 systematic evidence review also published in Menopause found that vaginal estrogen treatment doesn’t increase the risk of endometrial cancer or endometrial hyperplasia (abnormal thickening of the uterine lining).

Estradiol vaginal cream interactions

If you are using estradiol vaginal cream, you might be wondering if there are any foods (including grapefruit or grapefruit juice) or medications you need to avoid while using it. These are rare and unlikely, though. “Unlike estrogen pills, vaginal estrogen does not have known interactions with grapefruit, coffee, alcohol, or most medications,” Dr. January assures.

When it comes to drug interactions specifically, very little of the estrogen cream you use enters your bloodstream, according to Dr. January. There may be some exceptions, though. “If you are on blood thinners, hormonal medications, or chemotherapy, your medical team may still want to review everything,” Dr. January explains. Still, most people who use vaginal estrogen cream don’t need to change their medications.

All that said, before using estradiol vaginal cream, you should discuss any medications, supplements, or over-the-counter drugs you are taking with a healthcare professional.

Safety measures while using estradiol vaginal cream

Although estradiol vaginal cream is largely safe, there may be some populations who should take precautions. For instance, although very little estrogen gets into your bloodstream when using it, people with certain known or suspected conditions, including certain cancers or thrombotic disorders, might need to be cautious, according to Dr. Gaither.

According to DailyMed, people with the following conditions should not use estradiol vaginal cream:

• Abnormal vaginal bleeding
• History of active breast cancer
• Any estrogen-dependent cancer
• History of or active deep vein thrombosis or pulmonary embolism
• History of stroke or heart attack
• Known allergy to estradiol vaginal cream
• History of active liver disease
• Known thrombophilic disorder (blood clotting disorder)
• Known or suspected pregnancy

Although little is known about the impacts of estradiol vaginal cream and breastfeeding, estradiol vaginal cream is not recommended for breastfeeding women, according to Dr. Gaither. “Alternative non-hormonal treatments are preferred during breastfeeding,” she says.

How to avoid estradiol vaginal cream side effects

The best way to avoid estradiol vaginal cream side effects is to only use the medication as prescribed and to discuss any side effects you’re experiencing with a healthcare professional.

Here are some further tips from Dr. January:

• Start with the lowest effective dose.
• Use the cream only as prescribed; when it comes to vaginal estrogen cream, more is not better.
• If you are experiencing irritation, add in gentle vaginal moisturizers or lubricants.
• If irritation continues, consider pausing use of the estrogen cream and discuss it with a healthcare professional
• If you are experiencing any vaginal bleeding while using vaginal estrogen cream, contact your healthcare provider right away.

Estrogen Costs & Coupons

How to treat the side effects of estradiol vaginal cream

Most estradiol vaginal cream side effects can be treated by lowering the dose of your medication or trying a different brand of medication. “Most women do very well with vaginal estrogen once the right dose and routine are in place,” Dr. January says.

The majority of common side effects, like vaginal itching, burning, or breast pain, are not serious but should be discussed with your healthcare provider.

If you have any serious side effects of vaginal estrogen cream, including bulging eyes, stomach pain, nausea, loss of appetite, fever, dizziness, or vomiting, you should contact your health provider right away. If you have signs of an allergic reaction, like hives, trouble breathing, rashes, or swelling of your face, tongue, or throat, you should seek emergency medical care.

Bottom line: Is estradiol vaginal cream safe?

If you’re a menopausal or postmenopausal woman experiencing vaginal side effects of menopause like dryness, irritation, urinary urgency or frequency, or sexual discomfort, using estradiol vaginal cream can be helpful. Not only that, but it’s an overall very safe choice.

Estradiol vaginal cream “delivers estrogen directly to the vaginal tissue, with very little circulating throughout the body,” Dr. January says, adding that side effects are usually mild, short-lived, and that serious side effects are uncommon. “If vaginal symptoms are affecting your comfort, sexual health, or quality of life, this is a treatment worth considering and discussing with your healthcare provider,” she concludes.