Conjugated Estrogens & Medroxyprogesterone

Conjugated estrogens/medroxyprogesterone is prescription medication used to treat moderate to severe hot flashes and vaginal dryness, burning, and irritation after menopause. Conjugated estrogens/medroxyprogesterone is also used to reduce the risk of getting osteoporosis. This medicine both contain estrogen and progesterone hormones, which are necessary for many processes in the body and ovulation and menstruation.

Conjugated estrogens/medroxyprogesterone come in tablet form to be taken once daily, with or without food. Conjugated estrogens/medroxyprogesterone contains the same hormones, but may be packaged with different doses depending on the label.

Common side effects of conjugated estrogens/medroxyprogesterone include headache, breast pain, and irregular vaginal bleeding.

Conjugated estrogens/medroxyprogesterone is prescription medication used to treat moderate to severe hot flashes and vaginal dryness, burning, and irritation after menopause. Conjugated estrogens/medroxyprogesterone is also used to reduce the risk of getting osteoporosis.

These medications may be prescribed for other uses. Ask your doctor or pharmacist for more information. 

Conjugated Estrogens & Medroxyprogesterone may be found in some form under the following brand names:

• Premphase

• Prempro

Serious, but less common side effects include: 

• Heart attack
• Stroke
• Blood clots
• Dementia
• Breast cancer
• Cancer of the lining of the uterus (womb)
• Cancer of the ovary
• High blood pressure
• High blood sugar
• Gallbladder disease
• Liver problems
• Enlargement of benign tumors of the uterus (“fibroids”)
• Mental depression
• Severe allergic reaction

Call your healthcare provider right away if you get any of the following warning signs or any other unusual symptoms that concern you:

• New breast lumps
• Unusual vaginal bleeding 
• Changes in vision or speech
• Sudden new severe headaches
• Severe pains in your chest or legs with or without shortness of breath, weakness and fatigue
• Swollen lips, tongue and face

Less serious, but common side effects include:

• Headache 
• Breast pain 
• Irregular vaginal bleeding or spotting 
• Stomach or abdominal cramps, bloating 
• Nausea and vomiting 
• Hair loss 
• Fluid retention
• Vaginal yeast infection

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• St. John's Wort (Hypericum perforatum)
• phenobarbital
• carbamazepine
• rifampin
• erythromycin
• clarithromycin
• ketoconazole
• itraconazole
• ritonavir

​This is not a complete list of drug interactions. Ask your doctor or pharmacist for more information.

Important Information about the use of combinations of estrogens and progestin:

• Do not use estrogens with progestins to prevent heart disease, heart attacks, strokes, or dementia (decline of brain function)
• Using estrogens with progestins may increase your chances of getting heart attacks, strokes, breast cancer, or blood clots
• Using estrogens with progestins may increase your chance of getting dementia, based on a study of women 65 years of age or older
• Do not use estrogen-alone to prevent heart disease, heart attacks, strokes or dementia
• Using estrogen-alone may increase your chance of getting cancer of the uterus (womb)
• Using estrogen-alone may increase your chances of getting strokes or blood clots
• Using estrogen-alone may increase your chance of getting dementia, based on a study of women 65 years of age or older
• You and your healthcare provider should talk regularly about whether you still need treatment with conjugated estrogens/medroxyprogesterone

Do not take this medication if you have had your uterus (womb) removed (hysterectomy). The medication contains a progestin to decrease the chance of getting cancer of the uterus. If you do not have a uterus, you do not need a progestin and you should not take conjugated estrogens/medroxyprogesterone.

Do not take conjugated estrogens/medroxyprogesterone if you:

• Have unusual vaginal bleeding
• Currently have or have had certain cancers. Estrogens may increase the chance of getting certain types of cancers, including cancer of the breast or uterus.
If you have or have had cancer, talk with your healthcare provider about whether you should use conjugated estrogens/medroxyprogesterone.
• Had a stroke or heart attack
• Currently have or have had blood clots
• Currently have or have had liver problems
• Have been diagnosed with a bleeding disorder
• Are allergic to conjugated estrogens/medroxyprogesterone or any of this medication's ingredients
• Think you may be pregnant


Grapefruit and grapefruit juice may interact with this medication and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Tell your healthcare provider

• If you have any unusual vaginal bleeding. Vaginal bleeding after menopause may be a warning sign of cancer of the uterus (womb). Your healthcare provider should check any unusual vaginal bleeding to find out the cause.
• About all of your medical problems. Your healthcare provider may need to check you more carefully if you have certain conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, problems with your heart, liver, thyroid, kidneys, or have high calcium levels in your blood.
• About all the medicines you take. This includes prescription and nonprescription medicines, vitamins, and herbal supplements. Some medicines may affect how conjugated estrogens/medroxyprogesterone works. This medication may also affect how your other medicines work.
• If you are going to have surgery or will be on bedrest. You may need to stop taking estrogens and progestins.
• If you are breastfeeding. The hormones in this medication can pass into your milk.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. 

Tell your doctor if you are pregnant or plan to become pregnant. Conjugated estrogens/medroxyprogesterone should not be used during pregnancy.

Tell your doctor if you are breastfeeding or plan to breastfeed. Conjugated estrogens/medroxyprogesterone should not be used while breastfeeding.

• Take one conjugated estrogens/medroxyprogesterone tablet at the same time each day
• If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your normal schedule. Do not take 2 doses at the same time.
• Estrogens should be used at the lowest dose possible for your treatment only as long as needed. You and your healthcare provider should talk regularly (for example, every 3 to 6 months) about the dose you are taking and whether you still need treatment with conjugated estrogens/medroxyprogesterone.

Take conjugated estrogens/medroxyprogesterone exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. Your doctor will determine the best dose for you.

If you take too much conjugated estrogens/medroxyprogesterone call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If conjugated estrogens/medroxyprogesterone is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

What can I do to lower my chances of getting a serious side effect with conjugated estrogens/medroxyprogesterone?

• Talk with your healthcare provider regularly about whether you should continue taking conjugated estrogens/medroxyprogesterone.
• See your healthcare provider right away if you get vaginal bleeding while taking conjugated estrogens/medroxyprogesterone.
• Have a pelvic exam, breast exam and mammogram (breast X-ray) every year unless your healthcare provider tells you something else. If members of your family have had breast cancer or if you have ever had breast lumps or an abnormal mammogram, you may need to have breast exams more often.
• If you have high blood pressure, high cholesterol (fat in the blood), diabetes, are overweight, or if you use tobacco, you may have higher chances for getting heart disease. Ask your healthcare provider for ways to lower your chances of getting heart disease.

Store these medications at room temperature.

Keep all medications out of the reach of children.

WARNING: CARDIOVASCULAR DISORDERS, BREAST CANCER, ENDOMETRIAL CANCER and PROBABLE DEMENTIA

Estrogen Plus Progestin Therapy

Cardiovascular Disorders and Probable Dementia

Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.

The Women’s Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of deep vein thrombosis (DVT), pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.

The WHI Memory Study (WHIMS) estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

Breast Cancer

The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Estrogen-Alone Therapy

Endometrial Cancer

There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Cardiovascular Disorders and Probable Dementia

Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.

The WHI estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg), relative to placebo.

The WHIMS estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.