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Overview: Conjugated estrogens/medroxyprogesterone is a combination medicine used to replace hormones in the body to relieve symptoms of menopause and prevent osteoporosis after menopause. Common side effects are nausea, headache, or breast tenderness. Before taking conjugated estrogens/medroxyprogesterone, tell your health care provider about any health conditions or medicines you are taking. Get emergency help if you have trouble breathing, chest pain, vision changes, or trouble speaking. 

Uses

What is conjugated estrogens/medroxyprogesterone used for?

Conjugated estrogens/medroxyprogesterone is commonly used in people with a uterus for the following conditions.

Conjugated estrogens/medroxyprogesterone may also be used for other conditions as determined by your health care provider.

How does conjugated estrogens/medroxyprogesterone work (mechanism of action)?

Conjugated estrogens/medroxyprogesterone contains two kinds of hormones. Conjugated estrogens work by replacing estrogen, a hormone your body makes less of during menopause. Medroxyprogesterone is a progestin hormone that helps balance the effect of estrogen, decreasing the chance of uterine cancer while taking an estrogen-containing medicine. 

How is conjugated estrogens/medroxyprogesterone supplied (dosage forms)?

Brands and other names

  • Premphase
  • Prempro

Dosage forms and strengths

  • 0.3 mg/1.5 mg, 0.45 mg/1.5 mg, 0.625 mg/2.5 mg, 0.625 mg/5 mg oral tablets
  • 0.625 mg/5 mg and 0.625 mg oral tablets

How should I store conjugated estrogens/medroxyprogesterone?

Conjugated estrogens/medroxyprogesterone should be stored at room temperature, between 68 F and 77 F (20 C and 25 C). It can be exposed to temperatures between 59 F and 86 F (15 C and 30 C) for shorter periods of time, such as when transporting it. Store in a cool, dry place.

Side Effects

What are the most common side effects of conjugated estrogens/medroxyprogesterone?

The most common side effects of conjugated estrogens/medroxyprogesterone are listed below. Tell your health care provider if you have any of these side effects that bother you.

  • Stomach pain, cramping, or bloating
  • Back pain
  • Feeling unusually weak or tired
  • Headache
  • Gas, nausea, or vomiting
  • Depression (see below)
  • Itching
  • Breast pain or tenderness
  • Painful periods or irregular vaginal bleeding/spotting
  • Vaginal discharge or vaginal yeast infection
  • Hair loss
  • Fluid retention (see below)

There may be other side effects of conjugated estrogens/medroxyprogesterone that are not listed here. Contact your health care provider if you think you are having a side effect of a medicine. In the U.S., you can report side effects to the FDA at www.fda.gov/medwatch or by calling 800-FDA-1088 (800-332-1088). In Canada, you can report side effects to Health Canada at www.health.gc.ca/medeffect or by calling 866-234-2345.

What are the serious side effects of conjugated estrogens/medroxyprogesterone?

While less common, the most serious side effects of conjugated estrogens/medroxyprogesterone are described below, along with what to do if they happen.

Severe Allergic Reactions. Conjugated estrogens/medroxyprogesterone may cause allergic reactions, which can be serious. Stop taking conjugated estrogens/medroxyprogesterone and get help right away if you have any of the following symptoms of a serious allergic reaction.

  • Breathing problems or wheezing
  • Racing heart
  • Fever or general ill feeling
  • Swollen lymph nodes
  • Swelling of the face, lips, mouth, tongue, or throat
  • Trouble swallowing or throat tightness
  • Itching, skin rash, or pale red bumps on the skin called hives
  • Nausea or vomiting
  • Dizziness, feeling lightheaded, or fainting
  • Stomach cramps
  • Joint pain

Blood Clots. Conjugated estrogens/medroxyprogesterone may cause a blood clot in your arteries or veins and could cause a stroke, heart attack, or venous thromboembolism (VTE), including a blood clot in the lungs (pulmonary embolism), in the back of your eye (retinal vein occlusion), or in your legs or arms (deep venous thrombosis). Stop taking conjugated estrogens/medroxyprogesterone and get emergency help if you have any of the following signs of a blood clot.

  • Chest pain or pressure
  • Fast or abnormal heartbeat
  • Trouble breathing
  • Pain in your back, jaw, throat, or arm
  • Sweating, upset stomach, vomiting, or dizziness
  • Sudden weakness on one side of your body
  • Sudden and severe headache
  • Slurred speech or trouble understanding speech
  • Pain, swelling, or tenderness in your arm or leg
  • Vision loss
  • Bulging eyes
  • Double vision

Breast Cancer. You may be at higher risk for breast cancer if you take conjugated estrogens/medroxyprogesterone. Call your health care provider right away if you have any of the following symptoms.

  • New lump in your breast or armpit
  • Changes in the size, shape, texture, or temperature of your breast
  • Nipple changes

Ovarian Cancer. You may be at higher risk for cancer in your ovaries (ovarian cancer) if you take conjugated estrogens/medroxyprogesterone. Call your health care provider right away if you have any of the following symptoms.

  • Unusual vaginal discharge
  • Belly or back pain
  • Need to pee more often or urgently

Endometrial Cancer. You may be at higher risk for cancer in the lining of your uterus (endometrial cancer) if you take conjugated estrogens/medroxyprogesterone. Call your health care provider right away if you have any abnormal vaginal bleeding.

Dementia. Conjugated estrogens/medroxyprogesterone may increase your risk of a slowing of your brain function, especially if you are 65 or older. Tell your health care provider right away if you or your friends or family notice that you have any of the following.

  • Memory problems, such as asking the same question over and over
  • Confusion or disorientation
  • Trouble with complex but familiar tasks, such as cooking a meal or paying your bills
  • Personality changes, such as depression, agitation, paranoia, and mood swings

Gallbladder Problems. Taking conjugated estrogens/medroxyprogesterone can cause gallbladder problems, including cholecystitis and cholelithiasis (also known as gallstones). Call your health care provider right away if you have any of the following symptoms.

  • Your skin or the whites of your eyes turning yellowish in color (also called jaundice)
  • Fever
  • Pain in your upper stomach area
  • Stool (poop) that is clay-colored

Increased Blood Pressure (Hypertension). Conjugated estrogens/medroxyprogesterone may increase your blood pressure or make it worse if you have a history of high blood pressure. Call your health care provider if your blood pressure increases while taking this medicine.

Depression. Conjugated estrogens/medroxyprogesterone may cause changes in mood, including depression. Call your health care provider right away if you have new or increased depression or other unusual changes in mood or behavior. If you are about to harm yourself, call 911 or call or text 988, the Suicide & Crisis Lifeline.

Fluid Retention (Edema). Conjugated estrogens/medroxyprogesterone can cause fluid retention, also called edema. Fluid retention can cause serious problems in people with certain conditions, such as heart failure or kidney problems. Call your health care provider right away if you have any of the following symptoms.

  • Chest pain
  • Irregular heartbeat
  • Shortness of breath
  • Stretched or shiny skin
  • Swollen body parts, such as the belly or ankles

Increased Blood Sugar. Conjugated estrogens/medroxyprogesterone may increase your blood sugar levels. Talk to your health care provider about how to maintain healthy blood sugar levels.

Warnings & Precautions

Who should not use conjugated estrogens/medroxyprogesterone?

Allergies to Ingredients. People who are allergic to any of the following should not take conjugated estrogens/medroxyprogesterone.

  • Conjugated estrogens
  • Medroxyprogesterone
  • Prempro
  • Premphase
  • Any of the ingredients in the specific product dispensed

Your pharmacist can tell you all of the ingredients in the specific conjugated estrogens/medroxyprogesterone products they stock.

Unusual Vaginal Bleeding. Conjugated estrogens/medroxyprogesterone should not be used if you have bleeding from the uterus or vagina that is not part of the menstrual cycle or is abnormal. 

Cancer. Conjugated estrogens/medroxyprogesterone should not be used if you have, suspect you have, or had breast cancer, or a cancer that is sensitive to estrogen. These conditions could worsen if you use conjugated estrogens/medroxyprogesterone.

Blood Clots. Conjugated estrogens/medroxyprogesterone should not be used if you have or had blood clots, including a blood clot in the lungs (pulmonary embolism) or deep venous thrombosis (DVT). In addition, the medicine should not be used if you have a condition that makes your blood more prone to getting blood clots (thrombophilia). Conjugated estrogens/medroxyprogesterone can increase the risk of having a blood clot that could be dangerous, even fatal.

Heart Attack or Stroke. Conjugated estrogens/medroxyprogesterone should not be used if you have or had a stroke or heart attack. Conjugated estrogens/medroxyprogesterone can increase the risk of having a heart attack or stroke that could be dangerous, even fatal.

Liver Problems. Conjugated estrogens/medroxyprogesterone should not be used if your liver is not working as well as it should be. If there is a concern about the health of your liver, your health care provider may do tests to see if it is working well enough to take this medicine.

Pregnancy. Do not use conjugated estrogens/medroxyprogesterone if you are pregnant. If you become pregnant, contact your health care provider right away. See the Pregnancy section for more details

What should I know about conjugated estrogens/medroxyprogesterone before using it?

Do not take conjugated estrogens/medroxyprogesterone unless it has been prescribed to you by a health care provider. Take it as prescribed.

Do not share conjugated estrogens/medroxyprogesterone with other people, even if they have the same condition as you. It may harm them.

Keep conjugated estrogens/medroxyprogesterone out of the reach of children.

Take conjugated estrogens/medroxyprogesterone at about the same time each day.

People who are 65 and older can be at greater risk of some side effects from conjugated estrogens/medroxyprogesterone. Talk to your health care provider about your risks if you are in this age group.

Make sure to keep all follow up appointments with your health care provider. They will use these appointments to check if your dose or medicine needs to be changed. Estrogen-containing medicines should be used at the lowest possible dose for only as long as it is needed.

You should perform monthly self-breast exams and have regular pelvic exams (female exam), breast exams (done by a health care provider), and mammograms (x-ray to look closely at breast tissue) before taking conjugated estrogens/medroxyprogesterone and during treatment with it. Follow your health care provider’s recommendations for these.

What should I tell my health care provider before using conjugated estrogens/medroxyprogesterone?

Tell your health care provider about all of your health conditions and any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using. This will help them know if conjugated estrogens/medroxyprogesterone is right for you.

In particular, make sure that you discuss any of the following.

Current and Past Health Conditions. Tell your health care provider if you have any of the following.

Tobacco Use. Smoking and tobacco use can increase your risk of getting heart disease, which increases your risk of having a heart attack, stroke, or blood clots. Tell your health care provider if you use any tobacco products before starting conjugated estrogens/medroxyprogesterone. 

Upcoming Surgery or Bed Rest. You may be at increased risk for some side effects of conjugated estrogens/medroxyprogesterone if you do not move around normally for an extended period of time. Tell your health care provider if you have any upcoming surgeries or need to be on bed rest. Your health care provider can tell you if or when you need to stop taking conjugated estrogens/medroxyprogesterone.

High Triglyceride Levels. If you have high triglyceride levels, conjugated estrogens/medroxyprogesterone may make your triglycerides even higher. Very high triglyceride levels can lead to inflammation of the pancreas, which is called pancreatitis. Tell your health care provider if you have high triglyceride levels.

Uterine Fibroids. If you have benign tumors (fibroids) in your uterus, conjugated estrogens/medroxyprogesterone may cause them to get bigger. Some fibroids are small and cause no symptoms, while others may grow and cause problems. Talk to your health care provider if you have any of the following symptoms.

  • Heavy, long, painful periods
  • Pain in the lower belly or back
  • Painful sex
  • Peeing often 
  • Discomfort in the rectum

Hysterectomy. Conjugated estrogens/medroxyprogesterone contains a progestin to decrease the chances of getting cancer of the uterus. Tell your health care provider if you have had a hysterectomy and do not have a uterus.

Other Medicines and Supplements. Conjugated estrogens/medroxyprogesterone may interact with other medicines and supplements. Before taking conjugated estrogens/medroxyprogesterone, tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using. See the Interactions section for more details.

Pregnancy. People who can become pregnant are usually not prescribed conjugated estrogens/medroxyprogesterone. This medicine should not be used during pregnancy. Tell your health care provider if you are pregnant or plan to become pregnant. If you become pregnant while taking conjugated estrogens/medroxyprogesterone, stop taking the medicine right away and contact your health care provider.

Breastfeeding. Conjugated estrogens/medroxyprogesterone can pass into breast milk. Tell your health care provider if you are breastfeeding or plan to breastfeed. Your health care provider will let you know if you should use medroxyprogesterone while breastfeeding.

Interactions

Does conjugated estrogens/medroxyprogesterone interact with foods or drinks?

Eating grapefruit or drinking grapefruit juice while taking conjugated estrogens/medroxyprogesterone can increase the level of estrogens in your body. Talk to your health care provider if you eat grapefruit or drink grapefruit juice. 

It is unknown if drinking alcohol will affect conjugated estrogens/medroxyprogesterone. 

Does conjugated estrogens/medroxyprogesterone interact with other medicines (drug interactions)?

Always tell your health care provider about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements you are using.

In particular, make sure that you discuss if you are using any of the following before taking conjugated estrogens/medroxyprogesterone.

  • St. John’s wort, which is a supplement that may be used for depression
  • Phenobarbital, which is a medicine that may be used to treat seizures
  • Carbamazepine (Carbatrol, Tegretol, and others), which is a medicine commonly used to treat seizures or nerve pain
  • Rifampin (Rifadin), which is a medicine commonly used to treat an infection called tuberculosis
  • Clarithromycin or erythromycin (Ery-Tab and others), which is a medicine used for bacterial infections
  • Itraconazole (Sporanox, Tolsura) or ketoconazole, which is a medicine used for fungal infections
  • Ritonavir (Norvir), which is a medicine commonly used to treat HIV 

Many other medicines may alter the blood levels of conjugated estrogens/medroxyprogesterone. Tell your health care provider about all medicines that you take or have recently taken.

This may not be a complete list of medicines that can interact with conjugated estrogens/medroxyprogesterone. Always check with your health care provider.

Does interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose/Missed Dose

What should I do if I accidentally use too much conjugated estrogens/medroxyprogesterone?

If you or someone else has used too much conjugated estrogens/medroxyprogesterone, get medical help right away, call 911, or contact a Poison Control center at 800-222-1222.

What should I do if I miss a dose of conjugated estrogens/medroxyprogesterone?

If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and only take the next dose. Do not take double or extra doses.

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