Estradiol 0.1mg Patch (once Wk)
WARNING: Do not use this drug to prevent heart disease or dementia. A study of women taking an estrogen with a progestin showed a raised chance of heart attack, stroke, blood clot, breast cancer, and dementia. The chance of stroke, blood clot, and dementia was also raised when the estrogen was taken alone. Not all products and doses were studied. It is not known if the same effects may happen with this drug.The chance of endometrial cancer may be raised with the use of estrogen alone in patients with a uterus. Use of a progestin along with estrogen may lower the risk. Call your doctor right away if you have unexplained or long-lasting vaginal bleeding.Use this drug for the shortest time needed at the lowest useful dose. Your doctor will talk with you on a regular basis to see if you need to keep taking this drug. @ COMMON USES: It is used to prevent soft, brittle bones (osteoporosis) after menopause.It is used to prevent or lower the signs of the change of life (menopause).It is used to add estrogen to the body when the ovaries have been taken out or do not work the right way.It may be given to you for other reasons. Talk with the doctor.
Drug Class
Estrogen
Pharmacologic Class
Estrogen Receptor Agonist
Pregnancy Category
Category X
FDA Approved
Mar 1994
DEA Schedule
Not Controlled
Overview
What is this medicine?
Estradiol is a type of estrogen, a female hormone. This patch delivers estradiol through your skin to help relieve symptoms of menopause, such as hot flashes and night sweats, and to help prevent bone thinning (osteoporosis) after menopause. It works by replacing the estrogen your body no longer makes.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. It's essential to use this medication as directed.
Application Instructions
Apply this medication only to your skin, avoiding the mouth, nose, and eyes, as it may cause burning.
Use the medication at the same time every day to maintain a consistent routine.
Before and after applying the medication, wash your hands thoroughly.
Choose a clean, dry, and healthy area of skin on your lower belly or upper buttocks to apply the patch. Rotate the application site with each new patch to avoid skin irritation.
Avoid applying a patch to the same site for at least 7 days.
Do not apply the patch to skin with any problems, such as cuts, wounds, or irritated areas.
Avoid applying the patch to the breast or skin where you have recently used creams, oils, lotions, powder, or other skin products, as this may affect the patch's adhesion.
Select a hair-free area to apply the patch.
Avoid applying the patch to the waistline or areas that may cause the patch to come off when sitting.
Do not cut or divide the patches, and do not use damaged patches.
Managing the Patch
If the patch falls off, reapply it to the same site. If you cannot reapply the patch, apply a new one to a different area.
Wear only one patch at a time.
After removing a patch, fold the sticky sides together and dispose of it in a secure location, out of reach of children and pets.
Storage and Disposal
Store this medication at room temperature in a dry place, avoiding bathrooms.
Dispose of used patches and packaging in a secure location, out of reach of children and pets.
Missed Dose
If you miss a dose, apply a new patch as soon as you remember, after removing the old one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. It's essential to use this medication as directed.
Application Instructions
Apply this medication only to your skin, avoiding the mouth, nose, and eyes, as it may cause burning.
Use the medication at the same time every day to maintain a consistent routine.
Before and after applying the medication, wash your hands thoroughly.
Choose a clean, dry, and healthy area of skin on your lower belly or upper buttocks to apply the patch. Rotate the application site with each new patch to avoid skin irritation.
Avoid applying a patch to the same site for at least 7 days.
Do not apply the patch to skin with any problems, such as cuts, wounds, or irritated areas.
Avoid applying the patch to the breast or skin where you have recently used creams, oils, lotions, powder, or other skin products, as this may affect the patch's adhesion.
Select a hair-free area to apply the patch.
Avoid applying the patch to the waistline or areas that may cause the patch to come off when sitting.
Do not cut or divide the patches, and do not use damaged patches.
Managing the Patch
If the patch falls off, reapply it to the same site. If you cannot reapply the patch, apply a new one to a different area.
Wear only one patch at a time.
After removing a patch, fold the sticky sides together and dispose of it in a secure location, out of reach of children and pets.
Storage and Disposal
Store this medication at room temperature in a dry place, avoiding bathrooms.
Dispose of used patches and packaging in a secure location, out of reach of children and pets.
Missed Dose
If you miss a dose, apply a new patch as soon as you remember, after removing the old one.
Lifestyle & Tips
- Apply the patch to a clean, dry, hairless area of your lower abdomen or buttocks. Avoid applying it to your breasts or waistline.
- Rotate the application site each time you apply a new patch to prevent skin irritation.
- Do not apply the patch to irritated, cut, or oily skin.
- If the patch falls off, try to reapply it. If it doesn't stick, apply a new patch and continue your regular schedule.
- Avoid exposing the patch to direct sunlight or heat for prolonged periods.
- Discuss any concerns about diet, exercise, or smoking with your doctor, as these can impact your health while on hormone therapy.
- Regularly perform breast self-exams and attend scheduled mammograms and pelvic exams.
Available Forms & Alternatives
Available Strengths:
- Estradiol 0.05mg Patch (once Wk)
- Estradiol 0.1mg Patch (once Wk)
- Estradiol 1mg Tablets
- Estradiol 2mg Tablets
- Estradiol 0.5mg Tablets
- Estradiol 0.025mg Patch (once Wk)
- Estradiol 0.075mg Patch (once Wk)
- Estradiol Tds 0.0375mg Patches 4s
- Estradiol Tds 0.06mg Patch 4s
- Estradiol 0.025mg Patch (twice Wk)
- Estradiol 0.075mg Patch (twice Wk)
- Estradiol 0.0375mg Patch (twice Wk)
- Estradiol 0.1mg Patch (twice Wk)
- Estradiol 0.05mg Patch (twice Wk)
- Estradiol 0.0375mg Patch (twice Wk
- Estradiol 10mcg Vaginal Tabs 8s
- Estradiol 10mcg Vaginal Tabs 18s
- Estradiol 0.01% Vag Cream 42.5gm
- Estradiol Val 20mg/ml Inj, 5ml
- Estradiol Valerate 40mg/ml Inj, 5ml
- Estradiol Valerate 40mg/ml Inj, 5ml
- Estradiol 0.5mg/day Top Gel Pk
- Estradiol 0.5mg/day Top Gel Pk
- Estradiol 1mg/day Top Gel Pk
- Estradiol 1mg/day Top Gel Pk
- Estradiol 0.75mg/day Top Gel Pk
- Estradiol 0.75mg/day Top Gel Pk
- Estradiol 0.25mg/day Top Gel Pk
- Estradiol 0.25mg/day Top Gel Pk
- Estradiol 1.25mg/day Top Gel Pk
- Estradiol 1.25mg/day Top Gel Pk
- Estradiol Valerate 10mg/ml Inj, 5ml
- Estradiol Val 20mg/ml Inj, 5ml
- Estradiol Valerate 10mg/ml Inj, 5ml
- Estradiol 1.25mg/day Top Gel Pk
- Estradiol 0.75mg/day Top Gel Pk
- Estradiol 1mg/day Top Gel Pk
- Estradiol 0.5mg/day Top Gel Pk
- Estradiol 0.25mg/day Top Gel Pk
- Estradiol 0.06% Gel 37.5gm(pumps)
- Estradiol 0.06% Gel 37.5gm(pumps)
Dosing & Administration
Adult Dosing
Standard Dose:
Estradiol 0.1 mg/day transdermal patch applied once weekly. The patch should be applied to a clean, dry area of the trunk (excluding the breasts and waistline). Rotate application sites.
Dose Range:
0.025 - 0.1 mg
Condition-Specific Dosing:
vasomotorSymptoms:
Initial dose typically 0.025 mg/day, titrated up to 0.1 mg/day based on response and tolerability. 0.1 mg/day is often used for severe symptoms or when lower doses are ineffective.
preventionOfPostmenopausalOsteoporosis:
Typically 0.025 mg/day to 0.05 mg/day, but 0.1 mg/day may be used if higher estrogen levels are required and tolerated, or if osteoporosis is severe. Lowest effective dose should be used.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (Estradiol transdermal patches are not indicated for pediatric use. However, oral estradiol may be used for specific conditions like Turner syndrome or hypogonadism, with different dosing.)
Dose Adjustments
Renal Impairment:
Mild:
No specific dosage adjustment recommended.
Moderate:
No specific dosage adjustment recommended.
Severe:
Use with caution; monitor for adverse effects. Estrogens are primarily metabolized by the liver, but metabolites are renally excreted. Accumulation of metabolites may occur.
Dialysis:
Use with caution; monitor for adverse effects. Not dialyzable to a significant extent.
Hepatic Impairment:
Mild:
Use with caution; monitor for adverse effects. Estrogens are extensively metabolized by the liver.
Moderate:
Contraindicated due to impaired estrogen metabolism and increased risk of adverse effects.
Severe:
Contraindicated due to impaired estrogen metabolism and increased risk of adverse effects.
Pharmacology
Mechanism of Action
Estradiol is the primary estrogen secreted by the human ovary. It binds to and activates estrogen receptors (ERΞ± and ERΞ²) in target tissues, including the reproductive organs, breast, bone, and brain. This binding leads to gene transcription and protein synthesis, mediating the physiological effects of estrogen, such as the development and maintenance of the female reproductive system and secondary sex characteristics. In postmenopausal women, it replaces declining endogenous estrogen, alleviating vasomotor symptoms and preventing bone loss.
Pharmacokinetics
Absorption:
Bioavailability:
High (transdermal bypasses first-pass hepatic metabolism, leading to higher bioavailability compared to oral administration for the same dose, and a more favorable estradiol to estrone ratio).
Tmax:
Approximately 24-48 hours after patch application.
FoodEffect:
Not applicable for transdermal patch.
Distribution:
Vd:
Approximately 1.2 L/kg (for estradiol)
ProteinBinding:
Approximately 98% (primarily to sex hormone-binding globulin (SHBG) and albumin).
CnssPenetration:
Yes (estradiol crosses the blood-brain barrier).
Elimination:
HalfLife:
Approximately 1-2 hours (for circulating estradiol, but the patch provides continuous release, maintaining steady-state levels over the 7-day application period).
Clearance:
Approximately 650-1000 mL/min/1.73mΒ² (for estradiol)
ExcretionRoute:
Renal (primarily as glucuronide and sulfate conjugates), Biliary (minor).
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Within days to weeks for symptomatic relief (e.g., hot flashes).
PeakEffect:
Steady-state concentrations are typically reached within 1-2 days of initial patch application and maintained throughout the 7-day wear period.
DurationOfAction:
7 days (due to continuous release from the patch).
Safety & Warnings
BLACK BOX WARNING
Estrogens and progestins should not be used for the prevention of cardiovascular disease or dementia. The Women's Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50-79 years of age) during 5.6 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo. The WHI study also reported an increased risk of stroke and deep vein thrombosis in postmenopausal women (50-79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (0.625 mg) alone relative to placebo. The WHI Memory Study (WHIMS), an ancillary study of the WHI, reported an increased risk of probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) and in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily oral conjugated estrogens (0.625 mg) alone relative to placebo. It is unknown whether these findings apply to younger postmenopausal women. Other risks include endometrial cancer (in women with a uterus not receiving progestin), gallbladder disease, and ovarian cancer.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of gallbladder problems, such as:
+ Pain in the upper right belly area, right shoulder area, or between the shoulder blades
+ Yellow skin or eyes
+ Fever with chills
+ Bloating
+ Severe upset stomach or vomiting
Signs of pancreatitis (pancreas problems), including:
+ Severe stomach pain
+ Severe back pain
+ Severe upset stomach or vomiting
Signs of high blood pressure, such as:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Weakness on one side of the body
Trouble speaking or thinking
Changes in balance
Drooping on one side of the face
Blurred eyesight
Eyesight changes or loss
Bulging eyes
Changes in how contact lenses feel
Breast lump, pain, or soreness
Nipple discharge
Vaginal itching or discharge
Abnormal vaginal bleeding
Depression or other mood changes
Memory problems or loss
Fever
Difficulty urinating or changes in urine output
Pain while urinating
This medication may cause fluid retention, leading to swelling or weight gain. If you experience any of these symptoms, inform your doctor.
Blood Clots and High Calcium Levels
Seek immediate medical attention if you experience:
Signs of a blood clot, such as:
+ Chest pain or pressure
+ Coughing up blood
+ Shortness of breath
+ Swelling, warmth, numbness, changes in color, or pain in a leg or arm
+ Trouble speaking or swallowing
Signs of high calcium levels, including:
+ Weakness
+ Confusion
+ Fatigue
+ Headache
+ Upset stomach or vomiting
+ Constipation
+ Bone pain
Other Possible Side Effects
Most people do not experience severe side effects, but some may occur. If you notice any of the following symptoms, contact your doctor or seek medical attention if they bother you or do not go away:
Dizziness or headache
Hair loss
Upset stomach or vomiting
Constipation
Stomach pain or cramps
Bloating
Enlarged or tender breasts
Vaginal bleeding or spotting
Painful periods
Common cold symptoms
Nose or throat irritation
Weight gain or loss
Joint pain
Leg cramps
Changes in sex interest
Irritation at the site of administration
Reporting Side Effects
If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Signs of gallbladder problems, such as:
+ Pain in the upper right belly area, right shoulder area, or between the shoulder blades
+ Yellow skin or eyes
+ Fever with chills
+ Bloating
+ Severe upset stomach or vomiting
Signs of pancreatitis (pancreas problems), including:
+ Severe stomach pain
+ Severe back pain
+ Severe upset stomach or vomiting
Signs of high blood pressure, such as:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Weakness on one side of the body
Trouble speaking or thinking
Changes in balance
Drooping on one side of the face
Blurred eyesight
Eyesight changes or loss
Bulging eyes
Changes in how contact lenses feel
Breast lump, pain, or soreness
Nipple discharge
Vaginal itching or discharge
Abnormal vaginal bleeding
Depression or other mood changes
Memory problems or loss
Fever
Difficulty urinating or changes in urine output
Pain while urinating
This medication may cause fluid retention, leading to swelling or weight gain. If you experience any of these symptoms, inform your doctor.
Blood Clots and High Calcium Levels
Seek immediate medical attention if you experience:
Signs of a blood clot, such as:
+ Chest pain or pressure
+ Coughing up blood
+ Shortness of breath
+ Swelling, warmth, numbness, changes in color, or pain in a leg or arm
+ Trouble speaking or swallowing
Signs of high calcium levels, including:
+ Weakness
+ Confusion
+ Fatigue
+ Headache
+ Upset stomach or vomiting
+ Constipation
+ Bone pain
Other Possible Side Effects
Most people do not experience severe side effects, but some may occur. If you notice any of the following symptoms, contact your doctor or seek medical attention if they bother you or do not go away:
Dizziness or headache
Hair loss
Upset stomach or vomiting
Constipation
Stomach pain or cramps
Bloating
Enlarged or tender breasts
Vaginal bleeding or spotting
Painful periods
Common cold symptoms
Nose or throat irritation
Weight gain or loss
Joint pain
Leg cramps
Changes in sex interest
Irritation at the site of administration
Reporting Side Effects
If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Sudden severe headache, dizziness, or fainting
- Sudden vision changes (e.g., partial or complete loss of vision)
- Sudden numbness or weakness on one side of the body
- Sudden severe chest pain, shortness of breath, or coughing up blood
- Pain, swelling, or redness in one or both legs (especially in the calf)
- Yellowing of the skin or eyes (jaundice)
- Undiagnosed vaginal bleeding
- New breast lump or changes in existing breast lumps
- Severe abdominal pain or swelling
- Dark urine or light-colored stools
- Mood changes, depression
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, such as:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack
+ Stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Pregnancy or potential pregnancy. Note: This medication should not be taken during pregnancy.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, such as:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack
+ Stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Pregnancy or potential pregnancy. Note: This medication should not be taken during pregnancy.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will provide guidance on when to resume taking it after the surgery or procedure.
If you anticipate being immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as prolonged inactivity may increase your risk of developing blood clots. Additionally, if you have diabetes, it is crucial to closely monitor your blood sugar levels.
This medication may cause an increase in blood pressure, so it is essential to have your blood pressure checked regularly, as advised by your doctor. You should also have your blood work and bone density checked as recommended by your doctor.
Regular breast exams and gynecology check-ups are vital, and you should also perform breast self-exams as instructed by your doctor. The risk of certain side effects, such as heart attack, stroke, breast cancer, and ovarian cancer, may vary depending on factors like the duration of estrogen use, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor.
High triglyceride levels have been associated with this medication, so inform your doctor if you have a history of elevated triglyceride levels. This drug may also cause dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and use sunscreen and protective clothing and eyewear.
This medication may affect certain laboratory tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Smoking increases the risk of heart disease, so it is recommended that you do not smoke. Limit your alcohol consumption, and if you regularly drink grapefruit juice or eat grapefruit, discuss this with your doctor.
To maximize the effectiveness of this medication, use it in conjunction with calcium and vitamin D supplements, and engage in weight-bearing exercises like walking or physical therapy. Follow the diet and exercise plan recommended by your doctor.
In some cases, this medication may affect growth in children and teenagers, so they may require regular growth checks. Discuss this with your doctor. If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.
If you are breastfeeding, inform your doctor, as you will need to discuss any potential risks to your baby.
If you anticipate being immobile for extended periods, such as during long trips, bedrest after surgery, or illness, discuss this with your doctor, as prolonged inactivity may increase your risk of developing blood clots. Additionally, if you have diabetes, it is crucial to closely monitor your blood sugar levels.
This medication may cause an increase in blood pressure, so it is essential to have your blood pressure checked regularly, as advised by your doctor. You should also have your blood work and bone density checked as recommended by your doctor.
Regular breast exams and gynecology check-ups are vital, and you should also perform breast self-exams as instructed by your doctor. The risk of certain side effects, such as heart attack, stroke, breast cancer, and ovarian cancer, may vary depending on factors like the duration of estrogen use, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor.
High triglyceride levels have been associated with this medication, so inform your doctor if you have a history of elevated triglyceride levels. This drug may also cause dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and use sunscreen and protective clothing and eyewear.
This medication may affect certain laboratory tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Smoking increases the risk of heart disease, so it is recommended that you do not smoke. Limit your alcohol consumption, and if you regularly drink grapefruit juice or eat grapefruit, discuss this with your doctor.
To maximize the effectiveness of this medication, use it in conjunction with calcium and vitamin D supplements, and engage in weight-bearing exercises like walking or physical therapy. Follow the diet and exercise plan recommended by your doctor.
In some cases, this medication may affect growth in children and teenagers, so they may require regular growth checks. Discuss this with your doctor. If you are 65 or older, use this medication with caution, as you may be more susceptible to side effects.
If you are breastfeeding, inform your doctor, as you will need to discuss any potential risks to your baby.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Breast tenderness
- Abdominal pain
- Drowsiness/fatigue
- Withdrawal bleeding (in females)
What to Do:
Remove the patch immediately. Seek medical attention or call a poison control center (1-800-222-1222). Treatment is generally supportive.
Drug Interactions
Contraindicated Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) - concurrent use would counteract the effect of the aromatase inhibitor in breast cancer patients.
- Tranexamic acid (increased risk of thrombosis).
Major Interactions
- CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) - may decrease estradiol levels, reducing efficacy.
- CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir, grapefruit juice) - may increase estradiol levels, increasing risk of adverse effects.
- Thyroid hormone replacement therapy (e.g., levothyroxine) - estrogens can increase thyroid-binding globulin (TBG), potentially increasing the need for thyroid hormone.
- Corticosteroids (e.g., prednisone) - estrogens may decrease the clearance of corticosteroids, leading to increased corticosteroid effects and toxicity.
- Warfarin - estrogens may alter the anticoagulant effect of warfarin; monitor INR closely.
- Flibanserin - increased flibanserin exposure; contraindicated in patients with hepatic impairment.
Moderate Interactions
- Lamotrigine - estrogens may decrease lamotrigine levels, potentially leading to loss of seizure control.
- Cyclosporine - estrogens may inhibit cyclosporine metabolism, increasing cyclosporine levels and toxicity.
- Theophylline - estrogens may decrease theophylline clearance, increasing theophylline levels and toxicity.
- Bosentan - may decrease estradiol levels.
- Griseofulvin - may decrease estradiol levels.
Minor Interactions
- Acetaminophen - may increase estradiol levels by competing for sulfation.
- Ascorbic acid (Vitamin C) - may increase estradiol levels by competing for sulfation.
Monitoring
Baseline Monitoring
Complete Medical History and Physical Exam
Rationale: To identify contraindications, risk factors for cardiovascular disease, breast cancer, and other estrogen-related conditions.
Timing: Prior to initiation of therapy.
Blood Pressure
Rationale: Estrogens can cause fluid retention and may affect blood pressure.
Timing: Prior to initiation of therapy.
Lipid Panel
Rationale: Estrogens can affect lipid profiles; baseline assessment is important.
Timing: Prior to initiation of therapy.
Mammogram
Rationale: To screen for breast cancer, as estrogen therapy can increase breast cancer risk.
Timing: Prior to initiation of therapy, and as clinically indicated.
Pelvic Exam and Pap Smear
Rationale: To screen for gynecological conditions, including endometrial cancer (if uterus intact and progestin not co-administered).
Timing: Prior to initiation of therapy, and as clinically indicated.
Liver Function Tests (LFTs)
Rationale: To assess hepatic function, as estrogens are metabolized by the liver and are contraindicated in severe liver disease.
Timing: Prior to initiation of therapy, if clinically indicated.
Routine Monitoring
Annual Physical Exam
Frequency: Annually
Target: N/A
Action Threshold: N/A
Blood Pressure
Frequency: Annually, or more frequently if clinically indicated.
Target: <130/80 mmHg (general guideline)
Action Threshold: Sustained elevation (e.g., >140/90 mmHg) may require dose adjustment or discontinuation.
Mammogram
Frequency: As per national screening guidelines (e.g., annually or biennially).
Target: N/A
Action Threshold: New breast lump, abnormal mammogram findings.
Pelvic Exam and Pap Smear
Frequency: As per national screening guidelines (e.g., annually or every 3-5 years).
Target: N/A
Action Threshold: Abnormal bleeding, abnormal Pap smear findings.
Lipid Panel
Frequency: Periodically, as clinically indicated.
Target: Individualized based on cardiovascular risk.
Action Threshold: Significant adverse changes in lipid profile.
Bone Mineral Density (BMD)
Frequency: Every 1-2 years for osteoporosis prevention, or as clinically indicated.
Target: T-score > -2.5
Action Threshold: Significant bone loss despite therapy.
Symptom Monitoring
- New or worsening headache/migraine
- Unexplained vaginal bleeding
- Breast lumps or pain
- Leg pain, swelling, or tenderness (signs of DVT)
- Chest pain, shortness of breath, sudden cough (signs of PE)
- Sudden severe headache, vision changes, weakness/numbness (signs of stroke)
- Yellowing of skin or eyes (jaundice)
- Abdominal pain or swelling
- Mood changes, depression
- Fluid retention, swelling of ankles/feet
Special Patient Groups
Pregnancy
Contraindicated. Estradiol is not indicated for use in pregnancy and there is no benefit to estrogen therapy during pregnancy. Exposure to estrogens during pregnancy has been associated with an increased risk of birth defects in the reproductive organs of female fetuses.
Trimester-Specific Risks:
First Trimester:
Potential for adverse effects on fetal development, particularly reproductive organs.
Second Trimester:
Not indicated; continued exposure may pose risks.
Third Trimester:
Not indicated; continued exposure may pose risks.
Lactation
Contraindicated. Estrogens are excreted in human milk and can reduce the quantity and quality of breast milk. Potential adverse effects on the breastfed infant are unknown but generally considered to outweigh any potential benefits.
Infant Risk:
L5 (Contraindicated - significant documented hazard to infant or to milk production).
Pediatric Use
Not indicated for pediatric use. Safety and efficacy have not been established in pediatric patients. Use in children is generally limited to specific conditions like hypogonadism or Turner syndrome, typically with oral formulations and under specialist supervision.
Geriatric Use
Use with caution in women 65 years of age or older. The WHIMS study suggested an increased risk of probable dementia in women 65 years of age or older receiving estrogen alone or estrogen plus progestin. Consider the lowest effective dose for the shortest duration consistent with treatment goals. Monitor closely for cardiovascular events and cognitive changes.
Clinical Information
Clinical Pearls
- Transdermal estradiol bypasses first-pass hepatic metabolism, resulting in a more favorable estradiol to estrone ratio and potentially lower risk of VTE compared to oral estrogens, though VTE risk is still present.
- Always co-administer a progestin in women with an intact uterus to reduce the risk of endometrial hyperplasia and cancer.
- The 0.1 mg/day patch is the highest dose available and should be reserved for women with severe menopausal symptoms or significant bone loss who do not respond to lower doses.
- Patients should be advised to remove the old patch before applying a new one and to rotate application sites to prevent skin irritation.
- Regularly reassess the need for continued therapy, especially for long-term use, due to the associated risks (cardiovascular events, breast cancer, dementia).
Alternative Therapies
- Other systemic estrogen formulations (e.g., oral estradiol, conjugated estrogens, vaginal rings, gels, sprays)
- Selective Estrogen Receptor Modulators (SERMs) for osteoporosis (e.g., raloxifene, bazedoxifene)
- Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine)
- Bisphosphonates or other anti-resorptive agents for osteoporosis (e.g., alendronate, risedronate, denosumab)
- Bio-identical hormone therapy (compounded, not FDA-approved)
Cost & Coverage
Average Cost:
$100 - $300 per 4 patches (1 month supply)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (generic), Tier 3 (brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to ensure you receive the best possible care.