Estradiol 0.75mg/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 female hormone estrogen. It is applied to the skin to help relieve symptoms of menopause, such as hot flashes and vaginal dryness. It works by replacing the estrogen that your body no longer makes 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 is 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, healthy skin on the thigh.
Certain products are designed for specific areas of the body. Be sure to read the package insert to understand where to apply this medication.
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 Pump or Packet Products
If you are using a pump, prime it before the first use, following the instructions in the package insert.
Do not have someone else apply the medication to your skin. If someone else must apply it, they should wear gloves and avoid touching the medication.
Avoid exposure to fire, flames, or smoking until the medication is dry.
Allow the medication to dry 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 or open flames.
Keep all medications in a safe place, out of the reach of children and pets.
Missed Dose Instructions
If you miss a dose, apply it as soon as you remember.
If it is less than 12 hours until the next scheduled 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 is 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, healthy skin on the thigh.
Certain products are designed for specific areas of the body. Be sure to read the package insert to understand where to apply this medication.
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 Pump or Packet Products
If you are using a pump, prime it before the first use, following the instructions in the package insert.
Do not have someone else apply the medication to your skin. If someone else must apply it, they should wear gloves and avoid touching the medication.
Avoid exposure to fire, flames, or smoking until the medication is dry.
Allow the medication to dry 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 or open flames.
Keep all medications in a safe place, out of the reach of children and pets.
Missed Dose Instructions
If you miss a dose, apply it as soon as you remember.
If it is less than 12 hours until the next scheduled 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 one thigh 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 on the application site for at least one hour after application to prevent transfer.
- Regular exercise and a healthy diet can complement hormone therapy.
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:
0.75 mg estradiol applied once daily to the skin of one thigh
Dose Range:
0.25 - 1.5 mg
Condition-Specific Dosing:
vasomotor_symptoms:
Initial dose 0.25 mg or 0.5 mg once daily; may be adjusted based on clinical response to a maximum of 1.5 mg once daily. 0.75 mg is a common maintenance dose.
vulvar_vaginal_atrophy:
Initial dose 0.25 mg or 0.5 mg once daily; may be adjusted based on clinical response to a maximum of 1.5 mg once daily.
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.
Moderate:
No specific dose adjustment recommended.
Severe:
Use with caution; estrogens are primarily metabolized by the liver and excreted renally. Monitor for adverse effects.
Dialysis:
Use with caution; monitor for adverse effects. Not specifically studied.
Hepatic Impairment:
Mild:
Use with caution; estrogens are extensively metabolized by the liver. Monitor for adverse effects.
Moderate:
Contraindicated in severe liver dysfunction or disease.
Severe:
Contraindicated in severe liver dysfunction or disease.
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 tract, 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 menopausal women, it replaces declining endogenous estrogen levels to alleviate symptoms like vasomotor instability and genitourinary atrophy.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 10% (relative to oral estradiol, but topical avoids first-pass metabolism, leading to a more favorable estradiol to estrone ratio)
Tmax:
Approximately 2-4 hours
FoodEffect:
Not applicable for topical gel.
Distribution:
Vd:
Not specifically quantified for topical gel, but estrogens distribute widely throughout the body.
ProteinBinding:
Approximately 98% (primarily to sex hormone-binding globulin (SHBG) and albumin)
CnssPenetration:
Limited, but estrogen receptors are present in the CNS.
Elimination:
HalfLife:
Approximately 24-36 hours (for estradiol after topical application, reflecting sustained release from skin reservoir)
Clearance:
Not specifically quantified for topical gel.
ExcretionRoute:
Renal (as glucuronide and sulfate conjugates)
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Symptomatic relief may begin within weeks, full effect typically within 2-4 weeks.
PeakEffect:
Peak plasma concentrations reached within 2-4 hours after application.
DurationOfAction:
24 hours (applied once daily)
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) 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. Estrogens increase the risk of endometrial cancer in postmenopausal women with an intact uterus. Appropriate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurrent abnormal vaginal bleeding.
Side Effects
Serious 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 immediately or seek medical attention:
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, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes.
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or severe upset stomach or vomiting.
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe upset stomach or vomiting.
Signs of high blood pressure: severe headache or dizziness, passing out, or changes in eyesight.
Weakness on one side of the body, trouble speaking or thinking, changes in balance, drooping on one side of the face, or blurred eyesight.
Eyesight changes or loss, bulging eyes, or changes in how contact lenses feel.
Breast-related symptoms: lump in the breast, breast pain or soreness, or nipple discharge.
Vaginal symptoms: itching or discharge, or abnormal vaginal bleeding.
Depression or other mood changes, memory problems or loss, or fever.
Urinary problems: inability to pass urine or changes in urine output, or pain while passing urine.
This medication may cause fluid retention, leading to swelling or weight gain. If you experience swelling, weight gain, or trouble breathing, inform your doctor.
Blood Clots and High Calcium Levels
Seek medical help immediately 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
High calcium levels can occur in some people with cancer taking this medication. Contact your doctor right away if you experience:
Weakness
Confusion
Feeling tired
Headache
Upset stomach or vomiting
Constipation
Bone pain
Other Side Effects
Most people do not experience severe side effects, but some may occur. If you are bothered by any of the following side effects or if they persist, contact your doctor:
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
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 notice any of the following symptoms, contact your doctor immediately or seek medical attention:
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, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of liver problems: dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, vomiting, or yellow skin or eyes.
Signs of gallbladder problems: pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; fever with chills; bloating; or severe upset stomach or vomiting.
Signs of pancreatitis (pancreas problem): severe stomach pain, severe back pain, or severe upset stomach or vomiting.
Signs of high blood pressure: severe headache or dizziness, passing out, or changes in eyesight.
Weakness on one side of the body, trouble speaking or thinking, changes in balance, drooping on one side of the face, or blurred eyesight.
Eyesight changes or loss, bulging eyes, or changes in how contact lenses feel.
Breast-related symptoms: lump in the breast, breast pain or soreness, or nipple discharge.
Vaginal symptoms: itching or discharge, or abnormal vaginal bleeding.
Depression or other mood changes, memory problems or loss, or fever.
Urinary problems: inability to pass urine or changes in urine output, or pain while passing urine.
This medication may cause fluid retention, leading to swelling or weight gain. If you experience swelling, weight gain, or trouble breathing, inform your doctor.
Blood Clots and High Calcium Levels
Seek medical help immediately 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
High calcium levels can occur in some people with cancer taking this medication. Contact your doctor right away if you experience:
Weakness
Confusion
Feeling tired
Headache
Upset stomach or vomiting
Constipation
Bone pain
Other Side Effects
Most people do not experience severe side effects, but some may occur. If you are bothered by any of the following side effects or if they persist, contact your doctor:
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
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:
- Unusual vaginal bleeding (especially after menopause)
- New breast lump or changes in breasts
- Severe headache or migraine
- Sudden vision changes
- Numbness or weakness in an arm or leg, especially on one side of the body
- Trouble speaking or understanding speech
- Sudden shortness of breath or chest pain
- Pain, swelling, or redness in one leg
- Yellowing of the skin or eyes (jaundice)
- 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, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
A history of certain health conditions, including:
+ 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
Any instances of unexplained vaginal bleeding
If you are pregnant or think you might be pregnant. Note that 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, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
A history of certain health conditions, including:
+ 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
Any instances of unexplained vaginal bleeding
If you are pregnant or think you might be pregnant. Note that 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 inactivity 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 drug, so inform your doctor if you have a history of elevated triglyceride levels. This medication may cause dark skin patches on your face, so avoid exposure to sunlight, sunlamps, and tanning beds, and use protective measures like sunscreen, clothing, and eyewear.
This medication may interfere with certain laboratory tests, so notify all your healthcare providers and lab personnel that you are taking this drug. Avoid smoking, as it increases the risk of heart disease, and limit your alcohol consumption. If you regularly consume grapefruit juice or eat grapefruit, consult with your doctor.
In some cases, this medication may affect growth in children and teenagers, so 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 shortly 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. If you are breastfeeding, discuss the potential risks to your baby with your doctor.
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 inactivity 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 drug, so inform your doctor if you have a history of elevated triglyceride levels. This medication may cause dark skin patches on your face, so avoid exposure to sunlight, sunlamps, and tanning beds, and use protective measures like sunscreen, clothing, and eyewear.
This medication may interfere with certain laboratory tests, so notify all your healthcare providers and lab personnel that you are taking this drug. Avoid smoking, as it increases the risk of heart disease, and limit your alcohol consumption. If you regularly consume grapefruit juice or eat grapefruit, consult with your doctor.
In some cases, this medication may affect growth in children and teenagers, so 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 shortly 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. If you are breastfeeding, discuss the potential risks to your baby with your doctor.
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.
Drug Interactions
Major Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) - concurrent use would counteract their effect.
- Tranexamic acid - increased risk of thrombosis.
- Ombitasvir/paritaprevir/ritonavir with or without dasabuvir - increased ALT elevations.
Moderate Interactions
- CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) - may decrease estradiol levels.
- CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir, grapefruit juice) - may increase estradiol levels.
- Thyroid hormone replacement (e.g., levothyroxine) - estrogens can increase thyroid-binding globulin, potentially increasing thyroid hormone requirements.
- Corticosteroids - estrogens may decrease corticosteroid clearance, leading to increased effects.
- Warfarin - estrogens may alter anticoagulant effects; monitor INR.
Minor Interactions
- Folic acid - may increase folate levels.
Monitoring
Baseline Monitoring
Complete medical history and physical examination (including blood pressure, breast and pelvic exam)
Rationale: To identify contraindications, risk factors for cardiovascular disease, breast cancer, and other conditions.
Timing: Prior to initiation of therapy.
Lipid panel
Rationale: To assess cardiovascular risk factors.
Timing: Prior to initiation of therapy.
Liver function tests (LFTs)
Rationale: To assess hepatic function, as estrogens are metabolized by the liver.
Timing: Prior to initiation of therapy, especially if history of liver disease.
Mammogram
Rationale: To screen for breast cancer.
Timing: Prior to initiation of therapy, and as clinically indicated.
Routine Monitoring
Annual physical examination (including blood pressure, breast and pelvic exam)
Frequency: Annually
Target: Normal for age and health status
Action Threshold: Abnormal findings require further investigation.
Mammogram
Frequency: As clinically indicated (e.g., annually or biennially based on age and risk factors)
Target: No suspicious findings
Action Threshold: Suspicious findings require further diagnostic workup.
Endometrial monitoring (if uterus intact)
Frequency: Annually, or if abnormal bleeding occurs
Target: No endometrial hyperplasia or cancer
Action Threshold: Abnormal bleeding or endometrial thickening requires biopsy.
Lipid panel
Frequency: Periodically, as clinically indicated
Target: Optimal lipid levels
Action Threshold: Significant changes or worsening dyslipidemia may require intervention.
Symptom Monitoring
- Persistent or recurrent vaginal bleeding
- Breast lumps or pain
- Leg pain, swelling, or tenderness (signs of DVT)
- Sudden severe headache, vision changes, slurred speech (signs of stroke)
- Chest pain, shortness of breath (signs of MI or PE)
- Jaundice or abdominal pain (signs of liver dysfunction)
- Mood changes, depression
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. Estrogen therapy during pregnancy is associated with an increased risk of birth defects and should not be used.
Trimester-Specific Risks:
First Trimester:
Increased risk of birth defects, particularly cardiovascular and limb defects.
Second Trimester:
Not indicated; potential for adverse effects on fetal development.
Third Trimester:
Not indicated; potential for adverse effects on fetal development.
Lactation
Contraindicated during lactation. Estrogens are excreted in breast milk and may decrease the quantity and quality of breast milk. Potential for adverse effects on the nursing infant.
Infant Risk:
L5 (Contraindicated - significant documented risk to infant or to milk production)
Pediatric Use
Not indicated for pediatric use. Safety and efficacy have not been established in pediatric patients.
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 estrogen alone or estrogen plus progestin. Consider lowest effective dose and shortest duration consistent with treatment goals. Monitor closely for adverse cardiovascular and cognitive events.
Clinical Information
Clinical Pearls
- Topical estradiol gels offer an alternative to oral estrogens, avoiding first-pass hepatic metabolism and potentially leading to a more favorable estradiol to estrone ratio and lower triglyceride levels.
- Ensure patients understand proper application technique: apply to clean, dry, intact skin on one thigh, allow to dry, and wash hands thoroughly.
- Advise patients to avoid contact of the application site with others (especially children or pets) for at least one hour after application to prevent secondary exposure.
- For women with an intact uterus, a progestin must be co-administered to reduce the risk of endometrial hyperplasia and cancer.
- Regularly reassess the need for continued therapy, aiming for the lowest effective dose for the shortest duration consistent with treatment goals.
- Counsel patients on the Black Box Warnings regarding cardiovascular events, stroke, breast cancer, and dementia, and discuss individual risk factors.
Alternative Therapies
- Other topical estradiol formulations (patches, sprays, vaginal rings, vaginal creams, vaginal tablets)
- Oral estradiol (e.g., Estrace)
- Conjugated estrogens (e.g., Premarin, oral or vaginal cream)
- Estrogen/progestin combinations (e.g., Prempro, Combipatch)
- Selective Estrogen Receptor Modulators (SERMs) (e.g., ospemifene for dyspareunia, bazedoxifene/conjugated estrogens for vasomotor symptoms)
- 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)
Cost & Coverage
Average Cost:
Not available (varies widely by pharmacy, formulation, and insurance) per 30 packets
Generic Available:
Yes
Insurance Coverage:
Tier 2 or 3 (for brand), Tier 1 (for generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it is a good idea to consult with your pharmacist. If you have any questions or concerns about this medication, do not hesitate to discuss them with 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 reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the amount, and the time it occurred.