Estradiol 0.25mg/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 female hormone estrogen. It is applied to the skin to help relieve symptoms of menopause, such as hot flashes and vaginal dryness, by replacing the estrogen your body no longer makes enough of. It's important to use the lowest dose for the shortest time needed.
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.
Apply this medication only to your skin, as directed. Do not take it by mouth.
Keep the medication away from your mouth, nose, and eyes, as it may cause burning.
Use this medication at the same time every day to establish a routine.
Before and after applying the medication, wash your hands thoroughly.
Apply the medication to clean, dry, and healthy skin on your thigh. Be sure to choose the correct area of the body, as specified in the package insert.
Avoid applying the medication to skin with any problems or irritations.
Do not apply the medication to your face, breast, or vagina.
If you're using a pump, prime it before the first use, following the instructions in the package insert.
Apply the medication yourself, and avoid having someone else put it on you. If someone else must apply it, ensure they wear gloves and do not touch the medication.
Avoid exposure to fire, flames, or smoking until the medication is dry.
Allow the medication to 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 minimize skin irritation.
Storage and Disposal
Store this medication at room temperature in a dry place, away from bathrooms and heat sources. Protect it from open flames and keep it out of reach of children and pets.
Missed Dose
If you miss a dose, apply it as soon as you remember. However, if it's less than 12 hours until your next scheduled dose, skip the missed dose and resume your regular schedule. Do not apply two doses at the same time or take 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.
Apply this medication only to your skin, as directed. Do not take it by mouth.
Keep the medication away from your mouth, nose, and eyes, as it may cause burning.
Use this medication at the same time every day to establish a routine.
Before and after applying the medication, wash your hands thoroughly.
Apply the medication to clean, dry, and healthy skin on your thigh. Be sure to choose the correct area of the body, as specified in the package insert.
Avoid applying the medication to skin with any problems or irritations.
Do not apply the medication to your face, breast, or vagina.
If you're using a pump, prime it before the first use, following the instructions in the package insert.
Apply the medication yourself, and avoid having someone else put it on you. If someone else must apply it, ensure they wear gloves and do not touch the medication.
Avoid exposure to fire, flames, or smoking until the medication is dry.
Allow the medication to 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 minimize skin irritation.
Storage and Disposal
Store this medication at room temperature in a dry place, away from bathrooms and heat sources. Protect it from open flames and keep it out of reach of children and pets.
Missed Dose
If you miss a dose, apply it as soon as you remember. However, if it's less than 12 hours until your next scheduled dose, skip the missed dose and resume your regular schedule. Do not apply two doses at the same time or take extra doses.
Lifestyle & Tips
- Do not smoke, as smoking increases the risk of blood clots, stroke, and heart attack, especially when taking estrogen.
- Maintain a healthy weight and engage in regular physical activity to support cardiovascular health.
- Limit alcohol intake.
- Inform your doctor about all medications, supplements, and herbal products you are taking.
- Apply the gel to clean, dry skin on one thigh, avoiding the breasts and face. Allow it to dry for at least 5 minutes before dressing. Do not wash the application site for at least one hour after application.
- Avoid contact with other people's skin, especially children and pets, after applying the gel, until it is dry.
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:
0.25 mg of estradiol applied topically once daily to the skin of one thigh. The dose may be adjusted based on clinical response and symptoms, typically ranging from 0.25 mg to 1.25 mg per day.
Dose Range:
0.25 - 1.25 mg
Condition-Specific Dosing:
vasomotorSymptoms:
Initial dose 0.25 mg/day, adjust as needed.
vulvarAndVaginalAtrophy:
Initial dose 0.25 mg/day, adjust as needed.
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; no specific dose adjustment recommended but systemic exposure may be altered.
Dialysis:
Not available; use with caution.
Hepatic Impairment:
Mild:
Use with caution; no specific dose adjustment recommended.
Moderate:
Use with caution; estrogens are extensively metabolized by the liver. Consider lower starting doses and close monitoring.
Severe:
Contraindicated in severe hepatic dysfunction or disease.
Confidence:
Medium
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 the declining endogenous estrogen, alleviating symptoms like vasomotor symptoms and vulvar/vaginal atrophy.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 82% (relative to oral estradiol, but highly variable due to first-pass metabolism for oral forms; topical bypasses first-pass). Systemic absorption occurs from the skin.
Tmax:
Approximately 4-6 hours after topical application.
FoodEffect:
Not applicable for topical gel.
Distribution:
Vd:
Approximately 1.2 L/kg (for estradiol)
ProteinBinding:
Approximately 98% (primarily to sex hormone-binding globulin [SHBG] and albumin).
CnssPenetration:
Limited systemic penetration to CNS for therapeutic effects, but estrogen receptors are present in the brain.
Elimination:
HalfLife:
Approximately 1-2 hours (for estradiol itself, but effective half-life from topical reservoir is longer, leading to sustained levels).
Clearance:
High hepatic clearance.
ExcretionRoute:
Primarily renal (as glucuronide and sulfate conjugates), with some biliary excretion.
Unchanged:
<1% (very little unchanged drug excreted)
Pharmacodynamics
OnsetOfAction:
Symptomatic relief may begin within a few weeks; full effect for vasomotor symptoms typically within 4-8 weeks.
PeakEffect:
Peak plasma concentrations reached within 4-6 hours after application.
DurationOfAction:
Sustained systemic levels for 24 hours with once-daily application.
Safety & Warnings
BLACK BOX WARNING
Estrogens and estrogen plus progestin therapies 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) receiving daily oral conjugated estrogens (CE) plus medroxyprogesterone acetate (MPA) compared to placebo. The WHI estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis in postmenopausal women (50-79 years of age) receiving daily oral CE alone compared to placebo. The WHI Memory Study (WHIMS) reported an increased risk of probable dementia in postmenopausal women 65 years of age or older receiving CE plus MPA or CE alone compared to placebo. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adequate 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
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 other 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 immediate medical attention 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 (more common in people with cancer): weakness, confusion, fatigue, headache, stomach upset or vomiting, constipation, or bone pain.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only mild ones. If you are concerned about any of the following side effects or if they persist, contact your doctor:
Dizziness or headache.
Hair loss.
Stomach upset 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 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 other 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 immediate medical attention 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 (more common in people with cancer): weakness, confusion, fatigue, headache, stomach upset or vomiting, constipation, or bone pain.
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only mild ones. If you are concerned about any of the following side effects or if they persist, contact your doctor:
Dizziness or headache.
Hair loss.
Stomach upset 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 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:
- Sudden severe headache or migraine
- Sudden chest pain, shortness of breath, or coughing up blood
- Sudden vision changes (e.g., partial or complete loss of vision)
- Pain, swelling, or tenderness in one leg (especially the calf)
- Yellowing of the skin or eyes (jaundice)
- New breast lump or nipple discharge
- Unusual vaginal bleeding or spotting after menopause
- 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 sensitive to estrogen
Unexplained vaginal bleeding
Pregnancy or suspected pregnancy, as this medication should not be taken during pregnancy
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Do not initiate, stop, or adjust the dosage of any medication without consulting your doctor first.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, such as:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack
+ Stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Pregnancy or suspected pregnancy, as this medication should not be taken during pregnancy
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health problems with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Do not initiate, stop, or adjust the dosage of any medication without consulting your doctor first.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will provide guidance on when to resume taking it after the surgery or procedure.
If you 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. 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. Additionally, have your blood work and bone density checked as recommended by your doctor.
Regular breast exams and gynecology check-ups are vital, and you should also perform breast self-exams as instructed by your doctor. The risk of certain side effects, such as heart attack, stroke, breast cancer, and ovarian cancer, may vary depending on factors like the duration of estrogen use, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor.
High triglyceride levels have been associated with this drug. If you have a history of high triglyceride levels, inform your doctor. This medication may cause dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and use sunscreen and protective clothing and eyewear.
This medication may affect certain laboratory tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Avoid smoking, as it increases the risk of heart disease, and limit your alcohol consumption. If you regularly consume 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. 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. 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. Additionally, have your blood work and bone density checked as recommended by your doctor.
Regular breast exams and gynecology check-ups are vital, and you should also perform breast self-exams as instructed by your doctor. The risk of certain side effects, such as heart attack, stroke, breast cancer, and ovarian cancer, may vary depending on factors like the duration of estrogen use, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor.
High triglyceride levels have been associated with this drug. If you have a history of high triglyceride levels, inform your doctor. This medication may cause dark skin patches on your face, so it is essential to avoid sun exposure, sunlamps, and tanning beds, and use sunscreen and protective clothing and eyewear.
This medication may affect certain laboratory tests, so inform all your healthcare providers and lab personnel that you are taking this drug. Avoid smoking, as it increases the risk of heart disease, and limit your alcohol consumption. If you regularly consume 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. 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 women with a uterus)
What to Do:
There is no specific antidote. Treatment is symptomatic and supportive. Contact a poison control center or emergency medical services immediately. Call 1-800-222-1222.
Drug Interactions
Contraindicated Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole) - concurrent use would counteract their mechanism of action.
- Drugs that induce severe hepatic dysfunction.
Major Interactions
- CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) - may decrease estradiol levels, reducing efficacy.
- CYP3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole, ritonavir, grapefruit juice) - may increase estradiol levels, increasing risk of adverse effects.
- Thyroid hormone replacement therapy (e.g., levothyroxine) - estrogens can increase thyroid-binding globulin (TBG), potentially increasing thyroid hormone requirements.
- Anticoagulants (e.g., warfarin) - estrogens may decrease the anticoagulant effect of warfarin; monitor INR.
Moderate Interactions
- Corticosteroids (e.g., prednisone) - 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, reducing seizure control.
Minor Interactions
- Not many specific minor interactions for topical estradiol; general caution with drugs affecting liver metabolism.
Monitoring
Baseline Monitoring
Complete medical history and physical examination
Rationale: To identify contraindications, risk factors for cardiovascular disease, breast cancer, and other conditions.
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, as estrogens can increase risk.
Timing: Prior to initiation and as clinically indicated.
Lipid profile (total cholesterol, HDL, LDL, triglycerides)
Rationale: Estrogens can affect lipid metabolism.
Timing: Prior to initiation.
Liver function tests (LFTs)
Rationale: To assess hepatic function, as estrogens are metabolized by the liver.
Timing: Prior to initiation, especially if history of liver disease.
Routine Monitoring
Annual physical examination, including blood pressure, breast exam, and pelvic exam
Frequency: Annually
Target: Normal for age and health status
Action Threshold: Significant changes or abnormalities require further investigation.
Mammography
Frequency: As recommended by national guidelines (e.g., every 1-2 years)
Target: No suspicious findings
Action Threshold: New lumps, pain, or suspicious findings require immediate follow-up.
Assessment of symptoms (e.g., vasomotor symptoms, vaginal atrophy)
Frequency: Regularly (e.g., every 3-6 months initially, then annually)
Target: Symptom relief with lowest effective dose
Action Threshold: Persistent or worsening symptoms may require dose adjustment or re-evaluation of therapy.
Evaluation for abnormal vaginal bleeding
Frequency: Regularly, especially if uterus is intact
Target: Absence of abnormal bleeding
Action Threshold: Any new, persistent, or recurrent abnormal vaginal bleeding requires prompt investigation to rule out endometrial pathology.
Symptom Monitoring
- New or worsening headache/migraine
- Sudden severe chest pain or shortness of breath
- Sudden partial or complete loss of vision
- Pain, swelling, or redness in one leg (signs of DVT)
- Yellowing of skin or eyes (jaundice)
- Breast lumps or changes
- Abnormal vaginal bleeding
- Severe abdominal pain
- Mood changes, depression
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. Estrogen use 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 genital abnormalities in male fetuses.
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 adverse effects on the nursing infant are unknown but possible.
Infant Risk:
L5 (Contraindicated - significant documented hazard to infant or mother).
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 the lowest effective dose for the shortest duration. Close monitoring for adverse events is recommended.
Clinical Information
Clinical Pearls
- Topical estradiol gel bypasses first-pass hepatic metabolism, potentially leading to a more favorable estrogen-to-androgen ratio and less impact on liver-synthesized proteins compared to oral estrogens.
- Ensure patients understand the correct application technique: apply to clean, dry skin on one thigh, allow to dry, and avoid contact with others until dry. Do not apply to breasts or face.
- 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.
- Educate patients on the signs and symptoms of serious adverse events, such as blood clots, stroke, and heart attack, and when to seek immediate medical attention.
Alternative Therapies
- Selective Estrogen Receptor Modulators (SERMs) (e.g., ospemifene for dyspareunia, bazedoxifene/conjugated estrogens for vasomotor symptoms and osteoporosis prevention)
- 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)
- Lubricants and moisturizers for vaginal dryness
Cost & Coverage
Average Cost:
$100 - $300 per 30-day supply (e.g., 30 individual packets)
Generic Available:
Yes
Insurance Coverage:
Tier 2 or Tier 3 (for brand name); 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.