Key takeaways:
Premarin Vaginal Cream (conjugated estrogens) is a prescription medication used to treat certain symptoms of menopause, including vaginal dryness and painful sex.
Common side effects of Premarin Vaginal Cream include breast pain, headache, and changes to vaginal discharge. Some people also experience pelvic pain or vaginal pain and inflammation.
These side effects can often be managed with over-the-counter medications or lifestyle changes. Contact your healthcare team if your symptoms are too troublesome.
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When people hear the word “menopause,” they often think of hot flashes and nightsweats. But you may also experience a number of other symptoms. These include vaginal dryness and painful sex.
Premarin Vaginal Cream (conjugated estrogens) is a prescription medication used to manage these symptoms. It’s a type of menopausal hormone therapy (MHT) — previously known as hormone replacement therapy (HRT). It helps raise the level of estrogen in the body, which drops during menopause. Replacing estrogen can help relieve bothersome vaginal symptoms caused by menopause.
While it works well for menopause symptoms, Premarin Vaginal Cream can cause side effects. But it’s generally well tolerated. So what side effects can you expect?
Premarin vaginal cream side effects at a glance
Premarin Vaginal Cream has mostly local effects. This means it mainly works in the area where you apply it, unlike Premarin oral tablets, which have full-body effects. Because of this, Premarin Vaginal Cream doesn’t have as many side effects as the oral tablets.
Mild Premarin Vaginal Cream side effects include:
Breast tenderness or pain
Headache
Changes to vaginal discharge
Pelvic pain
Vagintis (pain or inflammation of the vagina)
Pain in other areas of the body
Fungal (yeast) infections
Muscle cramps
Dizziness
Rare but serious Premarin Vaginal Cream side effects and risks include:
Vaginal bleeding
Raised blood pressure
Vision problems
Changes to certain blood tests, such as calcium levels
Liver problems
Worsening of existing thyroid problems
Allergic reactions
This medication also has a few boxed warnings. This is the FDA’s strictest warning for medications. While rare, these side effects can be life-threatening. Premarin Vaginal Cream has the following boxed warnings:
A higher risk of breast cancer
A higher risk of uterine cancer
Blood clots, which could lead to heart attack or stroke
A higher risk of dementia
Below is information about five Premarin Vaginal Cream side effects, plus more detail on the medication’s boxed warnings.
1. Breast pain
The most commonly reported Premarin Vaginal Cream side effect is breast pain. You may be more likely to experience it if you’re applying the cream every day compared to applying it twice a week.
An over-the-counter (OTC) pain reliever, such as acetaminophen (Tylenol) or ibuprofen (Advil, Motrin), may help with breast pain. Some people also find cold compresses provide relief. Wearing loose-fitting shirts or bras might be helpful, too.
About estrogen supplements: Premarin Vaginal Cream (conjugated estrogens) is one of several estrogen supplements available for menopause symptom relief.
Typical dosages: Learn about typical Premarin Vaginal Cream dosages.
Cutting costs: Premarin Vaginal Cream doesn’t have to break the bank. Learn how you can save money on your prescription.
If your breast pain gets worse or becomes too bothersome, talk to your prescriber. Premarin Vaginal Cream may not be the right option for you.
2. Headache
Some people experience headaches when using Premarin Vaginal Cream. But this side effect is fairly uncommon. And headaches should be mild if they happen.
Like breast pain, headaches seem to be more common the more frequently you apply Premarin Vaginal Cream. Changing hormone levels may be the culprit behind these headaches.
Try these options for headache relief:
Increase the amount of water you’re drinking.
Optimize your sleep hygiene to help you get enough restful sleep.
Rest in a dark room while you have headache pain.
Try activities that can reduce stress levels, such as deep breathing or meditation.
Limit or avoid alcohol.
Ask a healthcare professional if you can safely take an occasional dose of OTC pain relievers.
Let your prescriber know if your headaches are severe or don’t improve with OTC medications. There may be something else causing them.
3. Change in vaginal discharge
After starting Premarin Vaginal Cream, you may notice more vaginal discharge than what’s typical for you. While bothersome, this side effect isn’t usually serious or dangerous.
But sometimes vaginal discharge changes can signal an infection. If you notice a change in the odor, color, or texture of your discharge, contact your healthcare team. These could be symptoms of a vaginal infection, such as a yeast infection.
If there’s ever blood in your discharge, contact your prescriber. This can be a sign of a more serious problem, such as endometrial (uterine) cancer.
4. Pelvic pain
Some people report experiencing pelvic pain while using Premarin Vaginal Cream. This could feel similar to period cramps for some people.
As with period cramps, OTC pain relievers may help ease this pelvic pain. You can also use a heating pad or hot water bottle. If this side effect seems severe, contact your prescriber. This isn’t typical with Premarin Vaginal Cream.
5. Vaginitis and other vaginal issues
Vaginitis is another possible Premarin Vaginal Cream side effect. You could also experience vaginal infections or thinning of vaginal tissue. This can be bothersome and make sex painful.
Keep in mind that in clinical trials, vaginitis was also reported by a similar percentage of participants using a placebo cream (a cream with no medication in it). So it’s possible that Premarin Vaginal Cream isn’t causing your vaginitis.
Avoid wearing tight-fitting clothes or douching. These can worsen vaginitis and raise the risk of vaginal infections. OTC personal lubricants may help relieve vaginal pain and make sex more comfortable. And you might need to use an OTC antifungal cream, such as Monistat (miconazole), if vaginitis is causing yeast infections.
If this Premarin Vaginal Cream side effect becomes too bothersome, let your prescriber know. They may suggest a different menopause medication.
What about the serious boxed warnings?
Premarin Vaginal Cream comes with a number of boxed warnings. These warnings are included on all estrogen-based MHT products. But the risk of these side effects is considered very low with Premarin Vaginal Cream.
Boxed warnings for Premarin Vaginal Cream include higher risks of:
Uterine cancer
Stroke
Dementia
Breast cancer, when combined with medroxyprogesterone (Provera)
Heart attack, when combined with medroxyprogesterone
These warnings are a result of several large studies, collectively called the Women's Health Initiative (WHI). The WHI looked at oral Premarin alone and in combination with medroxyprogesterone. The studies didn’t include lower-dose local estrogen medications such as Premarin Vaginal Cream. Even so, the serious side effects observed in the studies prompted the FDA to add the boxed warning to all estrogen-containing MHT products.
Many experts don’t believe the boxed warning for low-dose local estrogens is evidence-based. Organizations, such as the North American Menopause Society, have petitioned the FDA to remove these warnings from local estrogens. What’s more, an FDA advisory panel has recommended the agency remove them. But for now, the boxed warnings are still included on all estrogen-based MHTs.
Frequently asked questions
There is no standard answer when it comes to how long you should use Premarin Vaginal Cream. Everyone uses menopausal hormone therapy (MHT) for different lengths of time. But typically, most people don’t use these menopause treatments for more than 5 years. Your prescriber may suggest stopping Premarin Vaginal Cream as your menopause symptoms naturally decrease.
There are several alternatives to Premarin Vaginal Cream. Estradiol (Estrace) cream is the closest alternative and is applied in a similar way. There are also vaginal estradiol tablets (Yuvafem), inserts (Imvexxy), and rings (Estring). These medications all provide a low dose of estrogen, similar to Premarin Vaginal Cream.
Using too much Premarin Vaginal Cream is unlikely to cause serious harm. But it’s possible to experience side effects, such as nausea, stomach pain, or breast tenderness. If you’ve used too much Premarin Vaginal Cream, talk to your prescriber for guidance. You can also contact Poison Control at 1-800-222-1222 or online for guidance.
There is no standard answer when it comes to how long you should use Premarin Vaginal Cream. Everyone uses menopausal hormone therapy (MHT) for different lengths of time. But typically, most people don’t use these menopause treatments for more than 5 years. Your prescriber may suggest stopping Premarin Vaginal Cream as your menopause symptoms naturally decrease.
There are several alternatives to Premarin Vaginal Cream. Estradiol (Estrace) cream is the closest alternative and is applied in a similar way. There are also vaginal estradiol tablets (Yuvafem), inserts (Imvexxy), and rings (Estring). These medications all provide a low dose of estrogen, similar to Premarin Vaginal Cream.
Using too much Premarin Vaginal Cream is unlikely to cause serious harm. But it’s possible to experience side effects, such as nausea, stomach pain, or breast tenderness. If you’ve used too much Premarin Vaginal Cream, talk to your prescriber for guidance. You can also contact Poison Control at 1-800-222-1222 or online for guidance.
The bottom line
Premarin Vaginal Cream (conjugated estrogens) is a prescription medication used to treat vaginal symptoms of menopause. Common Premarin Vaginal Cream side effects include breast pain, headache, and changes to vaginal discharge. Some people also experience pelvic pain and vaginitis (inflammation of the vagina).
Mild Premarin Vaginal Cream side effects can typically be relieved with lifestyle changes or over-the-counter medications. Speak with your prescriber if you experience more serious symptoms, such as vaginal bleeding.
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References
Eglovitch, J. S. (2025). Panel urges FDA to remove boxed warning on women’s hormone therapy. Regulatory Focus.
Manson, J. E., et al. (2014). Why the product labeling for low-dose vaginal estrogen should be changed. Menopause.
Pinkerton, J. V., et al. (2020). Workshop on normal reference ranges for estradiol in postmenopausal women: commentary from The North American Menopause Society on low-dose vaginal estrogen therapy labeling. Menopause.
The Women's Health Initiative Steering Committee. (2004). Effects of conjugated equine estrogen in postmenopausal women with hysterectomy the Women's Health Initiative randomized controlled trial. JAMA.
Writing Group for the Women’s Health Initiative Investigators. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA.
Wyeth Pharmaceuticals. (2025). Premarin Vaginal- conjugated estrogens cream [package insert].
