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11 Side Effects of Premarin You Should Know About

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMPChristina Aungst, PharmD
Published on October 6, 2022

Key takeaways:

  • Premarin (conjugated estrogens) is a medication taken for certain symptoms of menopause — like hot flashes and night sweats.

  • The common side effects of Premarin include headache, sore breasts, and nausea. Some people report trouble sleeping, depression, and pain — but this isn’t as common.

  • If you experience Premarin side effects, they can often be managed with over-the-counter medication or a change in your dose. Contact your healthcare provider right away if you experience symptoms of a serious side effect.

  • There are several ways to save on Premarin. GoodRx can help you access Premarin at an exclusive cash price of $99 per month. Manufacturer savings cards and patient assistance programs are also available.

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Menopause is the time of life for women when estrogen levels fall and your periods stop for good. As estrogen levels go down, you may experience hot flashes, night sweats, and bothersome vaginal symptoms.

Premarin (conjugated estrogens) is a combination of different estrogens made from an animal source — the urine of pregnant horses. Premarin is most often used as hormone replacement therapy (HRT). HRT replaces hormones, such as estrogen, that your body makes less of as a result of menopause. This can help relieve moderate to severe symptoms of menopause, like hot flashes and night sweats.

Premarin is a tablet taken once per day. If you still have a uterus, you will also need to take a second medication — a progestin — with Premarin. This is to prevent extra growth of the tissue lining the uterus. 

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If you only have vaginal symptoms, Premarin tablets aren’t typically recommended. A personal lubricant or vaginal estrogen are the first choice for these types of menopause symptoms.

Like most medications, Premarin has some side effects you should be aware of. We’ll discuss 11 of the most notable side effects below.

1. Headache

Headache is the most common side effect of Premarin. Between 13 to 14% of people using Premarin during clinical studies experienced headache. The dose of Premarin does not seem to make a difference in how often a headache occurs.

Headaches are often associated with changes in hormone levels. Taking your Premarin dose at the same time every day may help prevent this side effect. 

If headaches do occur, over-the-counter (OTC) pain medications are a good option for treatment. This includes medications like acetaminophen (Tylenol) or ibuprofen (Advil, Motrin).

2. Breast pain

Breast pain or tenderness is another common side effect of Premarin. Higher doses of Premarin seem to cause this side effect more often than lower doses. 

Less often, Premarin may make your breasts larger. It can also increase your risk of breast cancer — more on that later. 

For sore breasts, an OTC pain reliever or cold compress may help. If it gets worse or becomes too bothersome, talk to your healthcare provider about other options.

3. Stomach pain, nausea, and gas

In some people, Premarin can cause stomach pain, nausea, and gas

Premarin can be taken with or without food. So taking it with food may help if it’s upsetting your stomach. You can also try an OTC medication for gas, like Gas-X. This may help relieve the pain caused by gas build-up in your gut.

Severe nausea or stomach pain is not normal. Discuss these symptoms with your healthcare provider if they occur. There may be something else going on.

4. Vaginal discharge

Up to 5% of people report an increase in vaginal discharge or irritation of the vagina (vaginitis) while using Premarin. In most cases, these side effects aren’t serious. But they can be bothersome and make sexual activity painful. Sometimes, these symptoms can be a sign of infection. If you notice an odor or change in the color or feel of the discharge, contact your healthcare provider.

Vaginitis may be treated with OTC personal lubricants to improve comfort. Hormone creams applied directly to the vagina may also help. Avoid douching and wearing tight clothing. This can increase your risk of vaginal infections and worsen vaginitis. 

If you notice blood in your discharge, contact your healthcare provider right away. This can be a symptom of a more serious side effect.

5. Pain

Premarin may also cause pain in areas other than the breasts and vagina. This is not a common side effect, but it’s still one to be aware of. Some people describe back pain, leg cramps, or pain in their pelvis while using Premarin. 

In general, feelings of pain can usually be managed with OTC pain medication. But if your pain is severe or in your chest, contact your healthcare provider right away. In this case, it may be a more serious issue.

6. Depression

Some people describe changes to their mental health during menopause. Often, taking Premarin will help improve your mood. But around 5% of people taking Premarin actually reported worse or new depression during clinical studies.

If you experience depression while taking Premarin, speak to your healthcare provider. They may suggest a non-hormonal medication for management of your menopausal symptoms. Some antidepressants — like paroxetine (Brisdelle) — may also be useful in managing hot flashes and night sweats.

7. Trouble sleeping

Like depression, some people notice an improvement in their sleep while taking Premarin. This is because it helps stop the night sweats and hot flashes caused by menopause. But some people find they have more trouble sleeping while taking Premarin.

If you have trouble sleeping, try taking Premarin in the morning. For some, this may help with insomnia. An OTC melatonin supplement may also be helpful. If you are unable to tolerate the sleep changes that come with HRT, talk to your healthcare provider. They may recommend a non-hormonal treatment for your menopausal symptoms.

8. Dementia

Premarin has been shown to increase the risk of developing dementia in women over the age of 65 years. The effect on younger women has not been studied. If you are over the age of 65 and considering Premarin, speak with your healthcare provider. They will discuss the possible risks and benefits with you first.

9. Gallbladder disease

Some people have had problems with their gallbladder while using Premarin. And some have needed their gallbladder removed. If you notice pain in the upper right side of your stomach, nausea, or yellow-colored eyes or skin, contact your healthcare provider. These may be symptoms of gallbladder disease.

10. Cardiovascular disorders (blood clots, heart attack, stroke)

The Women’s Health Initiative (WHI) was a nationwide study that looked for common causes of death in women after menopause. The WHI found an increased risk of blood clots, stroke, or heart attack in people taking Premarin plus a progestin. And an increased risk of stroke when Premarin was used alone. 

There are symptoms you should never ignore when taking Premarin:

  • Symptoms of blood clots in the lung — shortness of breath or chest pain

  • Symptoms of blood clots in the leg — leg pain or swelling

  • Symptoms of a stroke — trouble talking, walking, or drooping on one side of the face. Numbness, tingling, or weakness can also happen.

  • Symptoms of a heart attack — Severe chest pain, chest tightness, or pain that radiates up the arm, neck, or jaw

If you experience any of these symptoms, it is important to call 911 or seek emergency medical attention.

11. Increased risk of certain cancers

Premarin has been associated with an increased risk of endometrial and breast cancers.

Taking Premarin with a progestin decreases the risk of endometrial cancer. But it may increase the risk of developing breast cancer. However, the risk of developing breast cancer returns to normal within 3 years after stopping treatment. 

Generally, Premarin should be used at the lowest possible dose for the shortest amount of time necessary. This can be different for every woman. But the longer Premarin is taken, the more risk there is for serious side effects to happen. 

Be sure to perform regular breast exams to screen for any changes in your breast tissue. If you notice lumps, changes to the nipple, or pain, contact your healthcare provider. 

Unexplained vaginal bleeding, bloody discharge, or pelvic pain may be symptoms of endometrial cancer. Contact your healthcare provider if you notice any of these symptoms.

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

Mild side effects of Premarin can often be managed with OTC medications or changes to how or when you take your dose. If your side effects get worse or become troublesome, contact your healthcare provider. They can talk to you about other medications for your menopause symptoms.

If you have vaginal bleeding, severe pain, or other serious symptoms, contact your healthcare provider right away.

How to save on Premarin

There are ways to save on Premarin, which is available as a brand-name medication. GoodRx can help you navigate between patient assistance programs and copay savings cards to save money on your prescription:

  • Save with GoodRx: Anyone with a valid prescription, regardless of insurance status, can use GoodRx to purchase Premarin at an exclusive cash price of $99 per month.

  • Save with a copay savings card. If you have commercial insurance, you may be eligible to pay as little as $25 per month for Premarin tablets using a savings card from the manufacturer.

  • Save with a patient assistance program. If you’re uninsured or underinsured, you may be eligible for Premarin’s patient assistance program, which offers the medication free of cost.

The bottom line

Premarin is an HRT option used to treat moderate to severe symptoms of menopause. Common side effects of Premarin include headache, breast tenderness, and vaginal discharge. Some people also report trouble sleeping, depression, and pain while using Premarin.

Mild side effects of Premarin can often be managed with OTC medications or changes to how or when you take it. Contact your healthcare provider right away if you experience symptoms of a serious side effect, such as vaginal bleeding or chest pain.

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Why trust our experts?

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.
Stacia Woodcock, PharmD
Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.
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.

References

American Cancer Society. (2015). Menopausal hormone therapy and cancer risk.

Anderson, G. L., et al. (2004). Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. Journal of the American Medical Association.

View All References (7)

Baker, F. C., et al. (2018). Sleep and sleep disorders in the menopausal transition. Sleep Medicine Clinics.

Chlebowski, R. T., et al. (2020). Association of the menopausal hormone therapy with breast cancer incidence with mortality during long-term follow-up of Women’s Health Initiative clinical trials. Journal of the American Medical Association.

Maki, P. M., et al. (2012). Hormone therapy, dementia, and cognition: the Women’s Health Initiative ten years on. Climacteric.

North American Menopause Society. (2022). The 2022 hormone therapy position statement of The North American Menopause Society. Menopause: The Journal of The North American Menopause Society.

Rossouw, J. E., et al. (2002). Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. Journal of the American Medical Association.

Silberstein, S. D., et al. (1993). Sex hormones and headache. Journal of Pain and Symptom Management.

Wyeth Pharmaceuticals LLC. (2020). Premarin [package insert].

GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.

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