Estradiol 1.25mg/day Top Gel Pk
WARNING: All products: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.Skin gel and spray:Do not let another person or a pet touch this drug or the treated part of your skin. If they do, wash their skin with soap and water. If you notice any signs that others may have been in contact with the treated area by accident, call the doctor. This may include signs of unusual sexual development like breast changes in children. @ COMMON USES: It is used to prevent or lower the signs of the change of life (menopause).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
Jun 2007
DEA Schedule
Not Controlled
Overview
What is this medicine?
Estradiol gel is a medication containing the hormone estrogen. It is applied to the skin to help relieve symptoms of menopause, such as hot flashes, night sweats, and vaginal dryness. It works by replacing the estrogen that your body naturally produces less of after menopause.
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 and follow all instructions carefully.
Application Instructions
Do not take this medication by mouth. It is for use on your skin only.
Avoid getting the medication in your mouth, nose, or eyes, as it may cause burning.
Apply the medication at the same time every day.
Wash your hands before and after applying the medication.
Apply the medication to clean, dry, and healthy skin on the thigh.
Be sure to apply the medication to the correct area of the body, as specified in the package insert.
Do not apply the medication to skin with any problems or irritations.
Avoid applying the medication to the face, breast, or vagina.
Special Instructions for Certain Products
If you're using a pump, prime it before the first use, following the instructions in the package insert.
If you're using a packet, follow the instructions provided.
Do not have someone else apply the medication to your skin. If someone must assist you, they should wear gloves and avoid touching the medication.
Precautions
Avoid exposure to fire, flames, or smoking until the medication is dry.
Let the medication dry completely before covering the treated area with clothing.
Do not wash the treated area for at least 1 hour after applying the medication.
Rotate the application site with each dose to avoid skin irritation.
Storage and Disposal
Store the medication at room temperature in a dry place, away from bathrooms.
Protect the medication from heat and open flames.
Keep all medications in a safe place, out of the reach of children and pets.
Missed Dose
If you miss a dose, apply it as soon as you remember.
If it's less than 12 hours until the next dose, skip the missed dose and resume your regular schedule.
* Do not apply two doses at the same time or use extra doses.
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 and follow all instructions carefully.
Application Instructions
Do not take this medication by mouth. It is for use on your skin only.
Avoid getting the medication in your mouth, nose, or eyes, as it may cause burning.
Apply the medication at the same time every day.
Wash your hands before and after applying the medication.
Apply the medication to clean, dry, and healthy skin on the thigh.
Be sure to apply the medication to the correct area of the body, as specified in the package insert.
Do not apply the medication to skin with any problems or irritations.
Avoid applying the medication to the face, breast, or vagina.
Special Instructions for Certain Products
If you're using a pump, prime it before the first use, following the instructions in the package insert.
If you're using a packet, follow the instructions provided.
Do not have someone else apply the medication to your skin. If someone must assist you, they should wear gloves and avoid touching the medication.
Precautions
Avoid exposure to fire, flames, or smoking until the medication is dry.
Let the medication dry completely before covering the treated area with clothing.
Do not wash the treated area for at least 1 hour after applying the medication.
Rotate the application site with each dose to avoid skin irritation.
Storage and Disposal
Store the medication at room temperature in a dry place, away from bathrooms.
Protect the medication from heat and open flames.
Keep all medications in a safe place, out of the reach of children and pets.
Missed Dose
If you miss a dose, apply it as soon as you remember.
If it's less than 12 hours until the next dose, skip the missed dose and resume your regular schedule.
* Do not apply two doses at the same time or use extra doses.
Lifestyle & Tips
- Apply the gel to clean, dry skin on the thigh or calf once daily. Do not apply to breasts or face.
- Allow the gel to dry for at least 5 minutes before dressing.
- Wash hands thoroughly after application.
- Avoid contact with eyes and mouth.
- Avoid applying to irritated or broken skin.
- Avoid direct skin-to-skin contact with others (especially children or pets) on the application site for at least one hour after application to prevent transfer.
- Discuss the need for a progestin if you have a uterus, to reduce the risk of endometrial cancer.
- Maintain a healthy lifestyle, including regular exercise and a balanced diet.
- Quit smoking, as smoking increases the risk of serious cardiovascular events with estrogen use.
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:
1.25 mg estradiol applied once daily to the thigh or calf
Dose Range:
0.25 - 1.25 mg
Condition-Specific Dosing:
vasomotorSymptoms:
Initial dose 0.25 mg or 0.5 mg once daily; may be adjusted to 1.25 mg once daily based on clinical response. The 1.25 mg dose is often used for moderate to severe symptoms.
vulvarAndVaginalAtrophy:
Initial dose 0.25 mg or 0.5 mg once daily; may be adjusted based on clinical response.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (not indicated for pediatric use)
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, use with caution.
Moderate:
No specific dose adjustment recommended, use with caution.
Severe:
No specific dose adjustment recommended, use with caution; monitor for adverse effects.
Dialysis:
Not available; use with caution, as estrogen metabolism may be altered.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended for topical application, but use with caution.
Moderate:
Use with caution; estrogens are extensively metabolized by the liver. Consider lower starting doses and monitor for adverse effects.
Severe:
Contraindicated in severe hepatic impairment or liver disease.
Confidence:
Medium
Pharmacology
Mechanism of Action
Estradiol is the primary estrogen secreted by the human ovary. It binds to and activates nuclear estrogen receptors (ERΞ± and ERΞ²) in target tissues, forming a complex that interacts with DNA to regulate gene expression. This leads to the physiological effects of estrogens, including the alleviation of vasomotor symptoms and improvement of vulvar and vaginal atrophy.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 10-15% (transdermal, relative to oral)
Tmax:
Approximately 2-4 hours (for serum estradiol after single dose)
FoodEffect:
Not applicable for topical gel.
Distribution:
Vd:
Approximately 1.2 L/kg
ProteinBinding:
Approximately 98% (primarily to sex hormone-binding globulin [SHBG] and albumin)
CnssPenetration:
Limited (therapeutic effects are peripheral, though some CNS effects like mood modulation are known)
Elimination:
HalfLife:
Approximately 1-2 hours (for estradiol itself, but effective half-life from transdermal reservoir is longer, leading to sustained levels)
Clearance:
Approximately 650-900 mL/min/1.73mΒ²
ExcretionRoute:
Renal (primarily as glucuronide and sulfate conjugates), Fecal (minor)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Weeks to months for full therapeutic effect on vasomotor symptoms; some relief may be felt within days to weeks.
PeakEffect:
Typically achieved after several weeks of consistent daily application as steady-state levels are reached.
DurationOfAction:
24 hours (with daily application, maintaining steady-state levels)
Confidence:
Medium
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 0.625 mg/MPA 2.5 mg). The WHI Memory Study (WHIMS) reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older. These risks apply to systemic estrogen therapy. The relevance of these findings to topical estradiol gel is uncertain but cannot be excluded.
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: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of liver problems: dark urine, fatigue, decreased appetite, stomach pain or upset, light-colored stools, vomiting, or yellow skin and eyes.
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades, yellow skin and eyes, fever with chills, bloating, or severe stomach upset or vomiting.
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe stomach upset or vomiting.
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision.
Weakness on one side of the body, difficulty speaking or thinking, balance changes, drooping on one side of the face, or blurred vision.
Changes in eyesight or loss of eyesight, bulging eyes, or changes in how contact lenses feel.
Breast lump, breast pain or tenderness, or nipple discharge.
Vaginal itching or discharge.
Abnormal vaginal bleeding.
Depression or mood changes.
Memory problems or loss.
Fever.
Difficulty urinating or changes in urine output.
Pain while urinating.
This medication may cause fluid retention or swelling in the body. Inform your doctor if you experience swelling, weight gain, or breathing difficulties.
Blood Clots and High Calcium Levels
Seek medical help immediately if you experience:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, color changes, or pain in a leg or arm, or difficulty speaking or swallowing.
Signs of high calcium levels: weakness, confusion, fatigue, headache, stomach upset or vomiting, constipation, or bone pain.
Other Possible Side Effects
Most medications can cause side effects, but many people experience none or only mild side effects. If you experience any of the following side effects or any other symptoms that concern you or do not resolve, contact your doctor or seek medical help:
Dizziness or headache.
Hair loss.
Stomach upset or vomiting.
Constipation.
Stomach pain or cramps.
Bloating.
Breast enlargement or tenderness.
Vaginal bleeding or spotting.
Painful periods.
Common cold symptoms.
Nose or throat irritation.
Weight changes.
Joint pain.
Leg cramps.
Changes in sex drive.
This list is not exhaustive. 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 notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction: rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of liver problems: dark urine, fatigue, decreased appetite, stomach pain or upset, light-colored stools, vomiting, or yellow skin and eyes.
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades, yellow skin and eyes, fever with chills, bloating, or severe stomach upset or vomiting.
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe stomach upset or vomiting.
Signs of high blood pressure: severe headache or dizziness, fainting, or changes in vision.
Weakness on one side of the body, difficulty speaking or thinking, balance changes, drooping on one side of the face, or blurred vision.
Changes in eyesight or loss of eyesight, bulging eyes, or changes in how contact lenses feel.
Breast lump, breast pain or tenderness, or nipple discharge.
Vaginal itching or discharge.
Abnormal vaginal bleeding.
Depression or mood changes.
Memory problems or loss.
Fever.
Difficulty urinating or changes in urine output.
Pain while urinating.
This medication may cause fluid retention or swelling in the body. Inform your doctor if you experience swelling, weight gain, or breathing difficulties.
Blood Clots and High Calcium Levels
Seek medical help immediately if you experience:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, color changes, or pain in a leg or arm, or difficulty speaking or swallowing.
Signs of high calcium levels: weakness, confusion, fatigue, headache, stomach upset or vomiting, constipation, or bone pain.
Other Possible Side Effects
Most medications can cause side effects, but many people experience none or only mild side effects. If you experience any of the following side effects or any other symptoms that concern you or do not resolve, contact your doctor or seek medical help:
Dizziness or headache.
Hair loss.
Stomach upset or vomiting.
Constipation.
Stomach pain or cramps.
Bloating.
Breast enlargement or tenderness.
Vaginal bleeding or spotting.
Painful periods.
Common cold symptoms.
Nose or throat irritation.
Weight changes.
Joint pain.
Leg cramps.
Changes in sex drive.
This list is not exhaustive. 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:
- Unusual vaginal bleeding
- New breast lump or changes
- Pain, swelling, or redness in your leg (especially calf)
- Sudden chest pain or shortness of breath
- Sudden severe headache or migraine
- Sudden vision changes
- Yellowing of skin or eyes (jaundice)
- Severe abdominal pain
- Signs of an allergic reaction (rash, itching, swelling, severe dizziness, trouble breathing)
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 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 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 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 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 will be 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, you will need 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 crucial, 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. If you have a history of high triglyceride levels, inform your doctor. This drug may also cause 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 affect 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.
In some cases, this medication may affect growth in children and teenagers, and they may require regular growth checks. Consult with your doctor before using other medications or skin products, including soaps. When using the gel form of this medication, avoid applying sunscreen before or soon after application, and do not use sunscreen on the treated area for 7 consecutive days.
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 with your doctor to discuss any potential risks to your baby.
If you will be 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, you will need 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 crucial, 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. If you have a history of high triglyceride levels, inform your doctor. This drug may also cause 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 affect 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.
In some cases, this medication may affect growth in children and teenagers, and they may require regular growth checks. Consult with your doctor before using other medications or skin products, including soaps. When using the gel form of this medication, avoid applying sunscreen before or soon after application, and do not use sunscreen on the treated area for 7 consecutive days.
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 with 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:
Seek immediate medical attention or call a poison control center (1-800-222-1222). Treatment is generally supportive; there is no specific antidote. Remove the gel from the skin if possible.
Drug Interactions
Major Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) - concurrent use would counteract their effect.
- Tamoxifen - may reduce efficacy of tamoxifen and increase risk of VTE.
Moderate Interactions
- CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) - may decrease estradiol levels.
- CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, ketoconazole, itraconazole, ritonavir, grapefruit juice) - may increase estradiol levels.
- Thyroid hormones (e.g., levothyroxine) - estrogens may increase thyroid-binding globulin, requiring increased thyroid hormone dose.
- Corticosteroids (e.g., prednisone) - estrogens may decrease corticosteroid clearance, increasing their effects.
- Anticoagulants (e.g., warfarin) - estrogens may alter anticoagulant effects; monitor INR.
Minor Interactions
- Folic acid - may increase folate levels.
- Cyclosporine - estrogens may inhibit cyclosporine metabolism, increasing its levels.
Monitoring
Baseline Monitoring
Complete medical history and physical examination
Rationale: To identify contraindications, risk factors (e.g., VTE, breast cancer, cardiovascular disease), and establish baseline health status.
Timing: Prior to initiation of therapy
Blood pressure
Rationale: Estrogens can affect blood pressure.
Timing: Prior to initiation
Breast examination and mammography
Rationale: To screen for breast cancer and establish baseline breast health.
Timing: Prior to initiation and as clinically indicated
Pelvic examination and Pap test
Rationale: To screen for gynecological conditions and establish baseline uterine/ovarian health.
Timing: Prior to initiation and as clinically indicated
Lipid profile
Rationale: Estrogens can affect lipid metabolism; establish baseline.
Timing: Prior to initiation (if clinically indicated)
Liver function tests (LFTs)
Rationale: Estrogens are metabolized by the liver; establish baseline, especially if hepatic impairment is suspected.
Timing: Prior to initiation (if clinically indicated)
Routine Monitoring
Annual physical examination (including breast and pelvic exam)
Frequency: Annually
Target: Normal findings
Action Threshold: Any abnormal findings (e.g., new breast lump, abnormal bleeding) require immediate investigation.
Mammography
Frequency: As recommended by national guidelines (e.g., annually or biennially)
Target: Normal findings
Action Threshold: Suspicious findings require further diagnostic workup.
Blood pressure
Frequency: Periodically (e.g., every 6-12 months or as clinically indicated)
Target: <130/80 mmHg (general target)
Action Threshold: Sustained hypertension may require dose adjustment or discontinuation.
Symptoms of VTE, stroke, MI
Frequency: Ongoing patient education and inquiry at each visit
Target: Absence of symptoms
Action Threshold: Any new onset of chest pain, shortness of breath, leg pain/swelling, sudden severe headache, visual disturbances, or weakness/numbness requires immediate medical attention.
Symptom Monitoring
- New or worsening headache
- Unexplained vaginal bleeding
- Breast lumps or changes
- Pain, swelling, or tenderness in legs (DVT)
- Sudden chest pain or shortness of breath (PE)
- Sudden severe headache, visual disturbances, slurred speech, weakness/numbness (stroke)
- Chest pain, discomfort, or pressure (MI)
- Jaundice or signs of liver dysfunction (e.g., dark urine, pale stools, severe abdominal pain)
- Changes in mood or depression
Special Patient Groups
Pregnancy
Contraindicated during pregnancy. Estrogen use during pregnancy is associated with an increased risk of birth defects and should be avoided.
Trimester-Specific Risks:
First Trimester:
Increased risk of birth defects, particularly urogenital and cardiovascular abnormalities, if exposure occurs during critical periods of organogenesis.
Second Trimester:
Not applicable, as exposure should be avoided.
Third Trimester:
Not applicable, as exposure should be avoided.
Lactation
Not recommended during lactation. Estrogens are excreted in breast milk and may decrease the quantity and quality of breast milk. Potential adverse effects on the nursing infant are unknown but possible.
Infant Risk:
Risk L4 (Possibly hazardous). May decrease milk production and alter milk composition. Potential for adverse effects on infant development (e.g., feminization in male infants) is theoretical but not well-studied.
Pediatric Use
Not indicated for use in pediatric patients. Safety and efficacy have not been established.
Geriatric Use
Use with caution in women 65 years of age or older. The WHIMS study showed an increased risk of probable dementia in women 65 years of age or older receiving oral estrogen plus progestin or estrogen alone. The relevance to topical estradiol is not fully established but should be considered. Lowest effective dose for the shortest duration consistent with treatment goals is recommended.
Clinical Information
Clinical Pearls
- Topical estradiol gels offer the advantage of avoiding first-pass hepatic metabolism, potentially leading to a more favorable lipid profile and lower risk of VTE compared to oral estrogens, though the absolute risk reduction is not fully quantified for all outcomes.
- Ensure patients understand proper application technique: apply to a clean, dry, intact skin area (thigh or calf), allow to dry completely, and wash hands thoroughly.
- Emphasize the importance of consistent daily application for optimal symptom control.
- For women with an intact uterus, co-administration of a progestin is crucial to reduce the risk of endometrial hyperplasia and cancer.
- Regular monitoring for signs of serious adverse events (VTE, stroke, MI, breast cancer) is paramount, and patients should be educated on these warning signs.
- Re-evaluate the need for continued therapy periodically, typically annually, to ensure benefits outweigh risks.
Alternative Therapies
- Other systemic hormone therapies (e.g., conjugated estrogens, synthetic estrogens)
- Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine)
- Lifestyle modifications (e.g., diet, exercise, layered clothing, avoiding triggers)
- Vaginal moisturizers and lubricants for vulvar and vaginal atrophy
Cost & Coverage
Average Cost:
$150 - $300 per 30-day supply (30 packets)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (Brand), Tier 1 (Generic)
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 emergency medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.