5 Premarin Vaginal Cream Side Effects You Should Know About

When we hear the word “menopause,” we often think of hot flashes and nightsweats. But postmenopausal women often experience a number of other symptoms. These include vaginal dryness and painful sex.

Premarin (conjugated estrogens) vaginal cream is a prescription medication used to manage these symptoms. It’s a type of estrogen 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.

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 body-wide effects. Because of this, Premarin vaginal cream doesn't have many side effects. But it does have a few notable ones that you should know about. Below, we’ll discuss five of the most common Premarin vaginal cream side effects.

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1. Breast pain

The most commonly reported side effect of Premarin vaginal cream is breast pain. According to the medication’s package insert, up to 5% of women who used the medication in clinical trials experienced breast pain. This side effect seemed to be more common in those who applied Premarin vaginal cream daily, compared to those applying it twice weekly.

An over-the-counter (OTC) pain reliever like 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.

If your breast pain gets worse or becomes too bothersome, talk to your healthcare provider. Premarin vaginal cream may not be the right option for you.

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2. Headache

Some people experience headaches when using Premarin vaginal cream. However, this is fairly uncommon. The package insert states this side effect was reported by about 4% of clinical trial participants.

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.

OTC pain relievers can help with headaches. Let your healthcare provider know if your headaches are severe. 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. Between 2% and 3% of those who used the cream in clinical studies reported this side effect, according to the package insert.

While bothersome, a change in vaginal discharge isn’t usually serious or dangerous. But sometimes it can signal an infection. If you notice a change in the odor, color, or texture of your discharge, contact your healthcare provider. These could be symptoms of a vaginal infection.

If there’s ever blood in your discharge, contact your healthcare provider. This can be a sign of a more serious problem, such as endometrial 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 menstrual 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 healthcare provider.

5. Vaginitis and other vaginal issues

Vaginitis (pain or inflammation of the vagina) can happen while using Premarin vaginal cream. You could also experience vaginal infections or thinning of vaginal tissue. This can be bothersome and make sex painful. It’s important to note that in clinical trials, vaginitis was also reported by participants using a placebo cream (a cream with no medication in it).

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. OTC antifungal creams might be needed if vaginitis is causing yeast infections.

If this Premarin vaginal cream side effect becomes too bothersome, let your healthcare provider know. They may suggest an alternative.

What about the serious boxed warnings?

Premarin vaginal cream comes with a number of boxed warnings. These are the most serious warnings the FDA can require for a medication. The warnings listed for Premarin vaginal cream are included on all estrogen-based HRT medications. 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:

• Endometrial cancer

• Blood clots

• 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 (Provera). 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 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. Thus far, they’ve been unsuccessful, and the boxed warnings are still included.

When should I contact my healthcare provider about Premarin vaginal cream side effects?

Most Premarin vaginal cream side effects are mild. And they can often be relieved with OTC medications. If side effects seem extreme, contact your healthcare provider. They may recommend other medications or treatment options for your symptoms.

If you notice your vaginal discharge has an unusual smell, color, or texture, let your healthcare provider know. These can be symptoms of an infection. You may need treatment with an antibiotic or antifungal medication.

If you have vaginal bleeding or severe pain, reach out to your healthcare provider as soon as possible. These can be signs of serious health conditions and may not be caused by the cream.

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Written by:

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP, has over a decade of experience as a pharmacist, professor, and researcher. She was a full-time clinical professor in the pharmacy practice department at D’Youville School of Pharmacy before subsequently joining the faculty of the pharmacy practice department at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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