Please carefully read the following safety information regarding your prescriptions of estradiol/estriol products:
Risks and Precautions:
- Estrogen and progesterone therapies may increase the risk of blood clots, stroke, heart attack, and breast cancer, most often when used long-term or at higher doses.
- These medications are not recommended if you have a history of blood clots, stroke, heart disease, advanced liver disease, or certain cancers, unless specifically approved by your provider.
- Notify your healthcare provider immediately if you experience symptoms such as unusual chest pain, shortness of breath, severe headaches, vision changes, significant swelling, or unexpected vaginal bleeding.
Usage Guidelines:
- Take your medications exactly as prescribed by your healthcare provider.
- Do not share your medications with others.
- Inform your healthcare provider about all medications, supplements, and herbal products you are taking to avoid potential interactions.
Off Label:
- Compound medications, while regulated, are not FDA approved, and their use is considered off-label.
For any questions or concerns regarding your medication, contact our support team immediately.
This statement does not replace individual medical advice provided by your healthcare professional. Always follow the specific instructions given by your provider.
Important Estradiol/Estriol Safety Information
Black Box Warning
Warning: Risk of blood clot – There is a small, but definite, increased risk of blood clots with estradiol/estriol treatment. The risk is most pronounced in patients who have previously had a blood clot.
Warning: Risk of breast cancer – The Women’s Health Initiative study reported an increased risk of breast cancer in patients who are taking both estrogen as well as a synthetic progestin. The risk was not found to be statistically significant.
Warning: Risk of dementia, stroke, myocardial infarction – The Women’s Health Initiative study reported an increased risk of cardiovascular disease and dementia in some women taking estradiol/estriol. This risk was not found to be statistically significant.
Note regarding compounded medications – Compounded drugs are permitted to be prescribed under federal law but are not FDA-approved and do not undergo safety, effectiveness, or manufacturing review. Your Ivim Health provider may recommend certain doses of compounded medications based on your medical evaluation.
What is the FDA-approved use of estradiol/estriol?
Estradiol is approved by the FDA for the treatment of menopausal symptoms including hot flashes, vaginal or vulvar dryness and irritation, and the prevention of osteoporosis.
Limitations of use:
The combination of estradiol and estriol mimics the body’s own estrogen types. There is not a commercially available FDA approved product containing both forms of estrogen.
Who should not use estradiol/estriol?
You should not take estradiol/estriol if you have a history of breast cancer, a blood clot, uncontrolled cardiovascular disease, are pregnant or breastfeeding or have had a known allergic reaction to estradiol/estriol.
How should estradiol/estriol be administered?
Estradiol/estriol that works systemically (on the whole body) can be administered in multiple formulations including an oral capsule or tablet, a topical patch, or a sublingual film. Estradiol/estriol that works only locally in the vagina can be administered via a cream or gel, or a dissolvable tablet.
What should I tell my Ivim provider before starting estradiol/estriol?
Estradiol/estriol has certain drug interactions. It’s important to tell your Ivim provider all of the medications you are currently taking, including prescription, over-the-counter medications, vitamins, herbal and dietary supplements.
Medications to watch out for (interactions): Please note, this is not an exhaustive list, and interactions are not limited to the following medications.
- Anastrazole
- Antithrombin
- Argatroban
- Bivalirudin
- Dalteparin
- Enoxeparin
- Fezolinetant
- Fondaparinux
- Heparin
- Ospemifene
- Protamine
- Cimetidine
- St Johns Wort
It’s important to share your entire medical history with your provider. In particular, tell your provider if you have a history of:
- Breast cancer
- Uterine cancer
- Pulmonary embolism
- Deep vein thrombosis
- BRCA gene positive
- Pregnant or breastfeeding
- Endometriosis
- Cardiovascular disease (i.e., stroke, heart attack, hypertension)
What are the most serious side effects that I or a caregiver should monitor for?
If you are experiencing a medical emergency, call 911 or seek immediate medical attention.
The following serious side effects can occur with estradiol/estriol. You or a caregiver should carefully monitor for these side effects.
Blood clot (venous thromboembolism) – There is a small, but definite, increased risk of blood clots with estradiol/estriol treatment. The risk is most pronounced in patients who have previously had a blood clot. Some signs would be swelling of one leg, or shortness of breath.
Stoke and Heart attack – Although very rare, signs would include weakness of one side of the body, difficulty speaking, confusion, chest pain or pressure, and shortness of breath. Any of these symptoms should prompt urgent ED evaluation.
Serious Allergic Reactions: Stop using estradiol/estriol right away if you experience symptoms of a serious allergic reaction, including swelling of your face, lips, tongue or throat, severe rash or itching, very rapid heartbeat, problems breathing or swallowing, or fainting or feeling dizzy.
What are the most common side effects of estradiol/estriol?
- Headaches
- Mood changes
- Breast tenderness
- Acne
- Hair changes
- Weight gain
- Trouble sleeping
- Vaginal bleeding
- Irritability
This information is not comprehensive. Please see full prescribing information for estrogen patches and oral estrogen administration for complete safety information.
Disclaimer: Estradiol/estriol is available as a compounded medication through licensed compounding pharmacies. Compounded medications are not FDA-approved but are prepared by pharmacists to meet individual patient needs based on a valid prescription. The safety, efficacy, and quality of compounded estradiol/estriol may vary depending on the pharmacy and formulation. Always consult with a licensed healthcare provider before starting any compounded therapy.
This document may include information about the use of medications, supplements, or therapies that are not approved by the U.S. Food and Drug Administration (FDA) for the specific indication discussed. Such “off-label” use is based on clinical judgment, emerging research, or standard of care guidelines and is intended to support safe, evidence-informed decision-making.
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER, AND PROBABLE DEMENTIA
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 reduces the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Perform adequate diagnostic measures, including endometrial sampling when indicated, 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 Women’s Health Initiative (WHI) study reported increased risks of stroke and deep vein thrombosis (DVT). The WHI Memory Study (WHIMS) reported an increased risk of probable dementia in women 65 years of age and older.
- Use of estrogen-alone therapy should be limited to the shortest duration consistent with treatment goals and risks for the individual woman.
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 WHI study reported increased risks of myocardial infarction, stroke, pulmonary embolism, and DVT. The WHIMS reported an increased risk of probable dementia in women 65 years of age and older.
- Breast cancer: The WHI study reported increased risk of invasive breast cancer.
- Use of estrogen plus progestin therapy should be limited to the shortest duration consistent with treatment goals and risks for the individual woman.
