Estradiol 0.0375mg Patch (twice 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
Hormone Replacement Therapy (HRT)
Pharmacologic Class
Estrogen
Pregnancy Category
Category X
FDA Approved
Jan 1970
DEA Schedule
Not Controlled
Overview
What is this medicine?
Estradiol patches are a form of hormone replacement therapy (HRT) that deliver estrogen through your skin. They are used to relieve symptoms of menopause, such as hot flashes and vaginal dryness, and to help prevent bone loss. This specific patch delivers a low dose of estradiol and is typically changed twice a week.
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.
Administration
Do not take this medication by mouth. It is for skin use only.
Avoid getting the medication in your mouth, nose, or eyes, as it may cause burning.
Apply the patch at the same time every day to maintain a consistent routine.
Preparation and Application
Wash your hands before and after handling the patch to ensure cleanliness.
Choose a clean, dry, and healthy area of skin on your lower belly or upper buttocks for patch application.
Rotate the patch site with each new application to avoid skin irritation.
Wait at least 7 days before applying a new patch to the same site.
Do not apply the patch to skin with problems, such as cuts, wounds, or irritation.
Avoid applying the patch to the breast area.
Do not apply the patch to skin that has been treated with creams, oils, lotions, powder, or other skin products, as this may affect the patch's adhesion.
Select a hair-free area for patch application.
Avoid placing the patch on 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.
Patch Replacement and Disposal
If the patch falls off, reapply it to the same site. If it cannot be reapplied, attach a new patch to a different area.
Wear only one patch at a time.
After removing a used 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 the medication at room temperature in a dry place, avoiding bathroom storage.
Missed Dose
If you miss a dose, apply a new patch as soon as possible 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.
Administration
Do not take this medication by mouth. It is for skin use only.
Avoid getting the medication in your mouth, nose, or eyes, as it may cause burning.
Apply the patch at the same time every day to maintain a consistent routine.
Preparation and Application
Wash your hands before and after handling the patch to ensure cleanliness.
Choose a clean, dry, and healthy area of skin on your lower belly or upper buttocks for patch application.
Rotate the patch site with each new application to avoid skin irritation.
Wait at least 7 days before applying a new patch to the same site.
Do not apply the patch to skin with problems, such as cuts, wounds, or irritation.
Avoid applying the patch to the breast area.
Do not apply the patch to skin that has been treated with creams, oils, lotions, powder, or other skin products, as this may affect the patch's adhesion.
Select a hair-free area for patch application.
Avoid placing the patch on 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.
Patch Replacement and Disposal
If the patch falls off, reapply it to the same site. If it cannot be reapplied, attach a new patch to a different area.
Wear only one patch at a time.
After removing a used 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 the medication at room temperature in a dry place, avoiding bathroom storage.
Missed Dose
If you miss a dose, apply a new patch as soon as possible after removing the old one.
Lifestyle & Tips
- Do not smoke: Smoking significantly increases the risk of serious cardiovascular events (blood clots, stroke, heart attack) when using estrogen therapy.
- Maintain a healthy weight and engage in regular physical activity.
- Limit alcohol intake.
- Discuss any existing medical conditions or new symptoms with your doctor immediately.
- Apply the patch to a clean, dry area of skin on your lower abdomen or buttocks. Avoid breasts, waistline, or areas with skin folds. Rotate application sites.
- Ensure the patch adheres well and stays on for the full duration (3-4 days). If it falls off, replace it with a new one and continue your regular schedule from that point.
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:
0.0375 mg/day patch applied topically twice weekly (e.g., every 3-4 days)
Dose Range:
0.025 - 0.1 mg
Condition-Specific Dosing:
vasomotorSymptoms:
Initial dose typically 0.025 mg/day or 0.0375 mg/day, adjusted based on response and tolerability. Applied twice weekly.
vulvarAndVaginalAtrophy:
Often treated with lower doses or local preparations, but systemic 0.0375 mg/day patch can be used.
hypogonadism:
Initial dose typically 0.025 mg/day or 0.0375 mg/day, adjusted based on clinical response and serum estradiol levels.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
For treatment of hypogonadism, dosing is individualized, typically starting at lower doses (e.g., 0.025 mg/day patch) and titrating upwards. Not for general pediatric use.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment recommended.
Moderate:
No specific adjustment recommended, but use with caution.
Severe:
Use with caution; monitor for fluid retention and adverse effects.
Dialysis:
Not specifically studied; use with caution and monitor.
Hepatic Impairment:
Mild:
Use with caution; monitor liver function.
Moderate:
Use with caution; monitor liver function. Consider lower starting dose.
Severe:
Contraindicated in severe hepatic impairment or liver disease 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 central nervous system. This binding leads to gene transcription and protein synthesis, mediating the physiological effects of estrogen, such as the development and maintenance of female reproductive system and secondary sex characteristics, and regulation of the menstrual cycle. In postmenopausal women, it replaces declining endogenous estrogen levels to alleviate symptoms like vasomotor symptoms and genitourinary atrophy, and to prevent bone loss.
Pharmacokinetics
Absorption:
Bioavailability:
High (transdermal bypasses first-pass hepatic metabolism, leading to a more favorable estradiol-to-estrone ratio compared to oral administration).
Tmax:
Approximately 1-2 days after patch application.
FoodEffect:
Not applicable for transdermal patch.
Distribution:
Vd:
Approximately 1.2 L/kg (for estradiol).
ProteinBinding:
Approximately 98% bound to plasma proteins, primarily sex hormone-binding globulin (SHBG) and albumin.
CnssPenetration:
Limited, but estrogens do cross the blood-brain barrier and exert effects on the CNS.
Elimination:
HalfLife:
Approximately 1-2 hours (for circulating estradiol after removal of patch, but sustained release from patch provides continuous levels).
Clearance:
High (hepatic clearance).
ExcretionRoute:
Mainly renal (urine) as glucuronide and sulfate conjugates; some fecal excretion.
Unchanged:
<1% (very little unchanged estradiol excreted)
Pharmacodynamics
OnsetOfAction:
Symptomatic relief may begin within days to weeks.
PeakEffect:
Steady-state plasma concentrations are typically reached within 2-3 days of initial patch application.
DurationOfAction:
Maintained for the duration of patch wear (3-4 days for twice-weekly patches).
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 (CE 0.625 mg) alone, or in combination with medroxyprogesterone acetate (CE/MPA 0.625 mg/2.5 mg). The WHI Memory Study (WHIMS) reported an increased risk of probable dementia in postmenopausal women 65 years of age or older. These risks apply to other estrogen and progestin products as well. The 0.0375 mg/day patch is a lower dose than those studied in WHI, but the risks are still considered applicable to the class.
Side Effects
Important Side Effects to Report to Your Doctor Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, 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 problem), 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, weight gain, or breathing difficulties. If you experience any of these symptoms, inform your doctor.
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
In some cases, high calcium levels have been reported in people with cancer taking this medication. If you experience any of the following symptoms, contact your doctor:
Weakness
Confusion
Fatigue
Headache
Upset stomach or vomiting
Constipation
Bone pain
Other Possible Side Effects
Most people do not experience severe side effects, and some may only have minor side effects. However, if you experience any of the following side effects, consult your doctor or seek medical attention if they bother you or persist:
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
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult 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 experience any of the following symptoms, 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 problem), 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, weight gain, or breathing difficulties. If you experience any of these symptoms, inform your doctor.
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
In some cases, high calcium levels have been reported in people with cancer taking this medication. If you experience any of the following symptoms, contact your doctor:
Weakness
Confusion
Fatigue
Headache
Upset stomach or vomiting
Constipation
Bone pain
Other Possible Side Effects
Most people do not experience severe side effects, and some may only have minor side effects. However, if you experience any of the following side effects, consult your doctor or seek medical attention if they bother you or persist:
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
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult 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.
- Chest pain, shortness of breath, coughing up blood.
- Pain, swelling, or tenderness in one leg.
- Yellowing of the skin or eyes (jaundice).
- New breast lump or changes in existing breast lumps.
- Abnormal vaginal bleeding (especially if you have a uterus and are not taking progestin).
- Severe abdominal pain.
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 estrogen-dependent
Unexplained vaginal bleeding
Pregnancy or suspected pregnancy. Note: This medication is contraindicated during pregnancy and should not be taken if you are pregnant.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Do not initiate, stop, or adjust the dosage of any medication without first consulting 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 estrogen-dependent
Unexplained vaginal bleeding
Pregnancy or suspected pregnancy. Note: This medication is contraindicated during pregnancy and should not be taken if you are pregnant.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Do not initiate, stop, or adjust the dosage of any medication without first consulting your doctor.
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 immobility may increase your risk of developing blood clots. Additionally, if you have diabetes, it is crucial to closely monitor your blood sugar levels.
Be aware that medications like this one can cause high blood pressure. Follow your doctor's instructions for regular blood pressure checks. You should also have your blood work and bone density checked as directed 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.
This medication can cause elevated triglyceride levels. If you have a history of high triglyceride levels, inform your doctor. Prolonged use of this drug may lead to the development of dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and to use sunscreen and protective clothing and eyewear.
This medication may interfere with certain laboratory tests, so be sure to inform all your healthcare providers and lab personnel that you are taking this drug. Smoking can increase 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, it is recommended that you use it in conjunction with calcium and vitamin D supplements and engage in weight-bearing exercises, such as 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 regular growth checks may be necessary. 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. Finally, if you are breastfeeding, consult your doctor 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 immobility may increase your risk of developing blood clots. Additionally, if you have diabetes, it is crucial to closely monitor your blood sugar levels.
Be aware that medications like this one can cause high blood pressure. Follow your doctor's instructions for regular blood pressure checks. You should also have your blood work and bone density checked as directed 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.
This medication can cause elevated triglyceride levels. If you have a history of high triglyceride levels, inform your doctor. Prolonged use of this drug may lead to the development of dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and to use sunscreen and protective clothing and eyewear.
This medication may interfere with certain laboratory tests, so be sure to inform all your healthcare providers and lab personnel that you are taking this drug. Smoking can increase 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, it is recommended that you use it in conjunction with calcium and vitamin D supplements and engage in weight-bearing exercises, such as 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 regular growth checks may be necessary. 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. Finally, if you are breastfeeding, consult your doctor 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:
Overdose with transdermal patches is unlikely due to controlled release. Remove the patch immediately. Treatment is symptomatic and supportive. Call 911 or Poison Control (1-800-222-1222) for advice.
Drug Interactions
Contraindicated Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) - concurrent use would counteract the effect of the aromatase inhibitor.
- Tranexamic acid (increased risk of thrombosis).
Major Interactions
- CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) - may decrease estradiol levels and efficacy.
- CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir, grapefruit juice) - may increase estradiol levels and risk of adverse effects.
- Thyroid hormone replacement (e.g., levothyroxine) - estrogens can increase thyroid-binding globulin (TBG), potentially increasing thyroid hormone requirements.
- Anticoagulants (e.g., warfarin) - estrogens may alter the effects of anticoagulants; monitor INR/PT.
Moderate Interactions
- Corticosteroids - estrogens may decrease the clearance of corticosteroids, leading to increased effects.
- Cyclosporine - estrogens may inhibit cyclosporine metabolism, increasing its levels and toxicity.
- Lamotrigine - estrogens may decrease lamotrigine levels, potentially leading to loss of seizure control.
- Folic acid antagonists (e.g., methotrexate) - theoretical interaction, monitor.
Minor Interactions
- Not specifically identified as minor, but general caution with drugs affecting liver enzymes.
Monitoring
Baseline Monitoring
Complete medical history and physical examination
Rationale: To identify contraindications, risk factors (e.g., cardiovascular disease, breast cancer, liver disease), and establish baseline health status.
Timing: Prior to initiation of therapy.
Blood pressure
Rationale: Estrogens can affect blood pressure.
Timing: Prior to initiation of therapy.
Lipid profile
Rationale: Estrogens can affect lipid metabolism.
Timing: Prior to initiation of therapy.
Liver function tests (LFTs)
Rationale: To assess hepatic function, especially given hepatic metabolism of estradiol.
Timing: Prior to initiation of therapy.
Mammogram
Rationale: To screen for breast cancer before starting HRT.
Timing: Prior to initiation of therapy, as per screening guidelines.
Pelvic examination and Pap test
Rationale: To screen for gynecological conditions, including endometrial hyperplasia/cancer (if uterus intact and not on progestin).
Timing: Prior to initiation of therapy, as per screening guidelines.
Routine Monitoring
Annual physical examination, including blood pressure
Frequency: Annually
Target: Normal for age and health status
Action Threshold: Significant changes or sustained elevation warrant investigation and potential therapy adjustment.
Breast examination
Frequency: Annually (clinical breast exam) and mammogram as per screening guidelines
Target: No new lumps or abnormalities
Action Threshold: Any new or suspicious findings require immediate investigation.
Pelvic examination and Pap test
Frequency: Annually or as per screening guidelines (if uterus intact, monitor for abnormal bleeding)
Target: No abnormal findings
Action Threshold: Abnormal bleeding, pain, or suspicious findings require investigation.
Symptom review (e.g., vasomotor symptoms, vaginal dryness, mood, sleep)
Frequency: At each follow-up visit (e.g., every 3-6 months initially, then annually)
Target: Improved or resolved symptoms with minimal side effects
Action Threshold: Persistent or worsening symptoms, or bothersome side effects, warrant dose adjustment or consideration of alternative therapy.
Symptom Monitoring
- Signs of deep vein thrombosis (DVT) or pulmonary embolism (PE): leg pain, swelling, redness, shortness of breath, chest pain.
- Signs of stroke: sudden severe headache, vision changes, weakness or numbness on one side of the body, slurred speech.
- Signs of myocardial infarction (MI): chest pain, discomfort in other areas of the upper body, shortness of breath, cold sweat, nausea, lightheadedness.
- Signs of breast cancer: new lump, skin changes, nipple discharge.
- Signs of endometrial cancer (if uterus intact and not on progestin): abnormal vaginal bleeding, spotting, or discharge.
- Signs of liver problems: yellowing of skin/eyes (jaundice), dark urine, persistent nausea/vomiting, severe abdominal pain.
- Severe headache or migraine with aura (may indicate increased risk of stroke).
Special Patient Groups
Pregnancy
Contraindicated. Estradiol is classified as Pregnancy Category X. There is no indication for estrogen therapy in pregnancy, and there is evidence of fetal risk.
Trimester-Specific Risks:
First Trimester:
Potential for adverse effects on fetal development; not indicated.
Second Trimester:
Not indicated.
Third Trimester:
Not indicated.
Lactation
Not recommended. Estrogens can decrease the quantity and quality of breast milk. Small amounts of estrogens are excreted in breast milk and may have adverse effects on the nursing infant (e.g., breast enlargement, vaginal bleeding).
Infant Risk:
Low to moderate risk of adverse effects on infant; potential for decreased milk supply.
Pediatric Use
Not indicated for general pediatric use. Use in adolescent females with hypogonadism should be carefully considered and individualized by a specialist.
Geriatric Use
Use with caution. Women aged 65 years and older have an increased risk of probable dementia with estrogen-alone therapy. The lowest effective dose for the shortest duration consistent with treatment goals should be used. Increased risk of cardiovascular events and breast cancer also applies to this population.
Clinical Information
Clinical Pearls
- Always use the lowest effective dose for the shortest duration consistent with treatment goals, especially for menopausal symptoms.
- For women with an intact uterus, a progestin must be co-administered to reduce the risk of endometrial hyperplasia and cancer.
- Transdermal estradiol bypasses first-pass hepatic metabolism, potentially leading to a more favorable lipid profile and lower risk of venous thromboembolism compared to oral estrogens, though risks are still present.
- Advise patients to rotate application sites to prevent skin irritation and ensure consistent absorption.
- Emphasize the importance of regular follow-up appointments, including annual physical exams and mammograms.
- Educate patients on the signs and symptoms of serious adverse events (e.g., blood clots, stroke, heart attack, breast cancer) and when to seek immediate medical attention.
Alternative Therapies
- Other forms of estrogen (oral, vaginal cream/ring/tablet, gel, spray)
- Selective Estrogen Receptor Modulators (SERMs) (e.g., ospemifene for dyspareunia, bazedoxifene/conjugated estrogens for vasomotor symptoms and osteoporosis)
- Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine)
- Bio-identical hormone therapy (compounded preparations, variable efficacy and safety data)
- Lifestyle modifications (diet, exercise, stress reduction) for symptom management.
Cost & Coverage
Average Cost:
$100 - $400 per 8 patches (1 month supply)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or Tier 2 (generics often Tier 1, some brands Tier 2 or 3)
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 your 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 taken, the amount, and the time it happened.