Estradiol and progesterone (Oral)
Medically reviewed by Drugs.com. Last updated on Oct 21, 2021.
Estrogen Plus Progestin TherapyThe Women's Health Initiative (WHI) estrogen plus progestin substudy reported an increased risk of pulmonary embolism (PE), deep vein thrombosis (DVT), stroke and myocardial infarction (MI) 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 WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age and 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.Do not use estrogen plus progestogen therapy for the prevention of cardiovascular disease or dementia.The WHI estrogen plus progestin substudy reported increased risks of invasive breast cancer.Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestogen therapy, taking into account her individual risk profile.Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.Estrogen-Alone TherapyThere is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform 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.The WHI estrogen-alone substudy reported increased risks of stroke and DVT in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral CE (0.625 mg)-alone 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.Do not use estrogen-alone therapy for the prevention of cardiovascular disease or dementia.Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile.Prescribe estrogens with or without progestogens at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman .
Commonly used brand name(s)
In the U.S.
Available Dosage Forms:
Therapeutic Class: Endocrine-Metabolic Agent
Pharmacologic Class: Estrogen
Uses for estradiol and progesterone
Estradiol and progesterone combination is used to treat moderate to severe symptoms of menopause (eg, feelings of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating [hot flashes]) in women with a uterus.
Estradiol and progesterone is available only with your doctor's prescription.
Before using estradiol and progesterone
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For estradiol and progesterone, the following should be considered:
Tell your doctor if you have ever had any unusual or allergic reaction to estradiol and progesterone or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Appropriate studies have not been performed on the relationship of age to the effects of estradiol and progesterone combination in the pediatric population. Use of estradiol and progesterone combination is not indicated for use in children.
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of estradiol and progesterone combination in the geriatric population. However, elderly patients are more likely to have breast cancer, strokes, or dementia, which may require caution in patients receiving estradiol and progesterone combination.
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Interactions with medicines
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking estradiol and progesterone, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using estradiol and progesterone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.
- Tranexamic Acid
Using estradiol and progesterone with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
- Clavulanic Acid
- Eslicarbazepine Acetate
- Guar Gum
- Mycophenolate Mofetil
- Mycophenolic Acid
- Penicillin G
- Penicillin G Procaine
- Penicillin V
- St John's Wort
- Valproic Acid
Using estradiol and progesterone with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Interactions with food/tobacco/alcohol
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using estradiol and progesterone with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use estradiol and progesterone, or give you special instructions about the use of food, alcohol, or tobacco.
Other medical problems
The presence of other medical problems may affect the use of estradiol and progesterone. Make sure you tell your doctor if you have any other medical problems, especially:
- Abnormal or unusual vaginal bleeding or
- Bleeding problems or
- Blood clots (eg, deep vein thrombosis, pulmonary embolism), active or history of or
- Breast cancer, known or suspected, or a history of or
- Dementia or
- Heart attack, active or history of or
- Heart or blood vessel disease or
- Liver disease or
- Protein C, protein S, or antithrombin deficiency, or other known blood clotting disorders or
- Stroke, active or history of or
- Tumors (estrogen-dependent), known or suspected—Should not be used in patients with these conditions.
- Asthma or
- Cancer, history of or
- Diabetes or
- Edema (fluid retention or body swelling) or
- Endometriosis or
- Epilepsy (seizures) or
- Gallbladder disease or
- Hereditary angioedema (swelling of the face, lips, tongue, or throat) or
- Hypercalcemia (high calcium in the blood) or
- Hypercholesterolemia (high cholesterol or fats in the blood) or
- Hypertension (high blood pressure) or
- Hypocalcemia (low calcium in the blood) or
- Hypothyroidism (an underactive thyroid) or
- Jaundice during pregnancy or from using hormonal therapy in the past or
- Kidney disease or
- Liver tumors or
- Migraine headache or
- Obesity or
- Porphyria (enzyme problem) or
- Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.
Proper use of estradiol and progesterone
Take estradiol and progesterone only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.
Estradiol and progesterone should come with a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.
Take estradiol and progesterone with food.
Do not eat grapefruit or drink grapefruit juice while you are using estradiol and progesterone. Grapefruit and grapefruit juice may change the amount of estradiol and progesterone that is absorbed in the body.
The dose of estradiol and progesterone will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of estradiol and progesterone. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For oral dosage form (capsules):
- For moderate to severe hot flashes:
- Adults—One capsule once a day, in the evening. Each capsule contains 1 milligram (mg) estradiol and 100 mg progesterone.
- Children—Use is not recommended.
- For moderate to severe hot flashes:
If you miss a dose of estradiol and progesterone, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.
If you miss a dose and it is more than 2 hours until your next dose, take the missed dose as soon as possible with food, then go back to your regular time.
If you miss a dose and it is within 2 hours of your next evening dose, skip the missed dose and go back to your regular dosing schedule.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Precautions while using estradiol and progesterone
It is very important that your doctor check your progress at regular visits to make sure estradiol and progesterone is working properly and does not cause unwanted effects. These visits may be every 3 to 6 months. Pelvic exam, breast exam, and mammogram (breast x-ray) may be needed to check for unwanted effects, unless your doctor tells you otherwise. Be sure to keep all appointments.
It is unlikely that a postmenopausal woman may become pregnant. But, you should know that using estradiol and progesterone while you are pregnant could harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.
Using estradiol and progesterone over a long period of time may increase your risk of breast cancer or endometrial cancer. Talk with your doctor about this risk. Do not use estradiol and progesterone if you have had your uterus (womb) removed (hysterectomy). Check with your doctor immediately if you experience abnormal vaginal bleeding.
Using estradiol and progesterone may increase your risk of dementia, especially in women 65 years of age and older.
Using estradiol and progesterone may increase your risk for having blood clots, strokes, or heart attacks. This risk may continue even after you stop using the medicine. Your risk for these serious problems is even greater if you have high blood pressure, high cholesterol in your blood, diabetes, or if you are overweight or smoke cigarettes. Contact your doctor immediately if you experience chest pain, confusion, difficulty speaking, double vision, headaches, an inability to move arms, legs or facial muscle, or an inability to speak.
Tell the medical doctor or dentist in charge that you are using estradiol and progesterone before any kind of surgery (including dental surgery) or emergency treatment. Your doctor will decide whether you should continue using estradiol and progesterone. Estradiol and progesterone may also affect the results of certain medical tests.
Check with your doctor immediately if severe headache or sudden loss of vision or any other change in vision occurs while you are using estradiol and progesterone. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).
Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.
Estradiol and progesterone side effects
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
- Breast tenderness
- heavy non-menstrual vaginal bleeding
- pain in the pelvis
- white or brownish vaginal discharge
Incidence not known
- Blurred vision
- breast pain
- chest pain
- clay-colored stools
- dark urine
- decrease in the amount of urine
- fast or irregular heartbeat
- general feeling of discomfort or illness
- itching, skin rash
- lightheadedness, dizziness, or fainting
- loss of appetite
- noisy, rattling breathing
- stomach pain
- swelling of the fingers, hands, feet, or lower legs
- trouble breathing
- unpleasant breath odor
- unusual tiredness or weakness
- unusually heavy or unexpected menstrual bleeding
- vaginal bleeding or spotting
- vomiting of blood
- weight gain
- yellow eyes or skin
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Incidence not known
- Muscle spasms
- night sweats
- pain in the arms or legs
- sleepiness or unusual drowsiness
- stomach discomfort or swelling
- trouble sleeping
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
Frequently asked questions
More about estradiol / progesterone
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- During pregnancy
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- Drug class: sex hormone combinations
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