Estradiol 0.06% Gel 37.5gm(pumps)
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
Hormone Replacement Therapy (HRT)
Pharmacologic Class
Estrogen Receptor Agonist
Pregnancy Category
Category X
FDA Approved
Jan 2003
DEA Schedule
Not Controlled
Overview
What is this medicine?
Estradiol gel is a medication containing the hormone estrogen, which is naturally produced by a woman's body. It is used to 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. The gel is applied to the skin, usually on the arm, once a day.
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.
Apply this medication only to your skin, avoiding ingestion or contact with 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 one arm, from the wrist to the shoulder. Avoid using it on skin with any problems or irritations.
Do not apply this medication to your face, breast, or vagina.
Before the first use, prime the pump according to the manufacturer's instructions.
It is recommended that you apply the medication yourself. If someone else must apply it, they should wear gloves and avoid touching the medication.
After applying the medication, avoid exposure to fire, flames, or smoking until it is completely dry.
Allow the medication to dry before covering the area with clothing.
Do not bathe, shower, or swim immediately after applying the medication.
Storage and Disposal
To store this medication properly:
Keep it at room temperature in a dry place, avoiding storage in a bathroom.
Protect the medication from heat or open flames.
If using a pump, discard any unused portion after the labeled number of doses have been used.
Missed Dose
If you miss a dose, follow these steps:
Use the missed dose as soon as you remember.
If it is less than 12 hours until your next scheduled dose, skip the missed dose and continue with your regular schedule.
Do not use 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 is essential to use this medication as directed.
Apply this medication only to your skin, avoiding ingestion or contact with 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 one arm, from the wrist to the shoulder. Avoid using it on skin with any problems or irritations.
Do not apply this medication to your face, breast, or vagina.
Before the first use, prime the pump according to the manufacturer's instructions.
It is recommended that you apply the medication yourself. If someone else must apply it, they should wear gloves and avoid touching the medication.
After applying the medication, avoid exposure to fire, flames, or smoking until it is completely dry.
Allow the medication to dry before covering the area with clothing.
Do not bathe, shower, or swim immediately after applying the medication.
Storage and Disposal
To store this medication properly:
Keep it at room temperature in a dry place, avoiding storage in a bathroom.
Protect the medication from heat or open flames.
If using a pump, discard any unused portion after the labeled number of doses have been used.
Missed Dose
If you miss a dose, follow these steps:
Use the missed dose as soon as you remember.
If it is less than 12 hours until your next scheduled dose, skip the missed dose and continue with your regular schedule.
Do not use two doses at the same time or take extra doses.
Lifestyle & Tips
- Apply the gel to clean, dry skin on one arm (from wrist to shoulder) 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.
- Do not allow others to come into contact with the application site until the gel is dry, especially children or pets.
- Discuss any concerns about long-term use with your doctor, as hormone therapy should be used for the shortest duration possible at the lowest effective dose.
- Maintain regular physical activity and a healthy diet to support bone health and cardiovascular health.
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:
Apply 1.25 g of gel (0.75 mg estradiol) once daily to one arm from the wrist to the shoulder.
Dose Range:
0.625 - 2.5 mg
Condition-Specific Dosing:
vasomotorSymptoms:
Initial dose 1.25 g (0.75 mg estradiol) once daily. May be adjusted between 0.625 g (0.375 mg estradiol) and 2.5 g (1.5 mg estradiol) daily based on individual response and tolerability.
vulvarAndVaginalAtrophy:
Initial dose 1.25 g (0.75 mg estradiol) once daily. May be adjusted between 0.625 g (0.375 mg estradiol) and 2.5 g (1.5 mg estradiol) daily based on individual response and tolerability.
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, but use with caution.
Moderate:
No specific dose adjustment recommended, but use with caution.
Severe:
No specific dose adjustment recommended, but use with caution. Monitor for adverse effects.
Dialysis:
Not available
Hepatic Impairment:
Mild:
Use with caution; estrogens are extensively metabolized by the liver. Consider lower starting dose.
Moderate:
Use with caution; estrogens are extensively metabolized by the liver. Consider lower starting dose and close monitoring.
Severe:
Contraindicated in severe liver 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 organs, breast, bone, and brain. This binding leads to gene transcription and protein synthesis, mediating the physiological effects of estrogen, such as the alleviation of vasomotor symptoms and prevention of bone loss in postmenopausal women.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 82% (relative to oral estradiol, due to avoidance of first-pass metabolism)
Tmax:
Approximately 2-4 hours (for estradiol and estrone)
FoodEffect:
Not applicable (topical administration)
Distribution:
Vd:
Not available (for transdermal gel, but generally high for estradiol)
ProteinBinding:
Approximately 98% (primarily to sex hormone-binding globulin (SHBG) and albumin)
CnssPenetration:
Limited (estradiol can cross the blood-brain barrier, but clinical significance for gel is related to central effects on vasomotor symptoms)
Elimination:
HalfLife:
Approximately 24-36 hours (for estradiol after transdermal application, due to sustained absorption)
Clearance:
Not available
ExcretionRoute:
Renal (primarily as glucuronide and sulfate conjugates)
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Days to weeks for symptomatic relief
PeakEffect:
Weeks to months for full therapeutic effect
DurationOfAction:
24 hours (with daily application)
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 probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily oral CE/MPA. It is unknown whether these risks apply to younger postmenopausal women. 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 CE alone. The WHIMS also reported an increased risk of probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily oral CE alone. Other doses of oral conjugated estrogens and other dosage forms of estrogens and progestins were not studied in the WHI and, in the absence of comparable data, these risks should be assumed to be similar. 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.
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 immediately or seek emergency 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 lump, breast pain or soreness, 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, 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 immediate medical attention if you experience:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, changes in color, or pain in a leg or arm; or trouble speaking or swallowing.
Signs of high calcium levels (more common in people with cancer): weakness, confusion, fatigue, headache, upset stomach or vomiting, constipation, or bone pain.
Other Possible Side Effects
While many people may not experience side effects or only have mild ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Dizziness or headache.
Hair loss.
Upset stomach or vomiting.
Constipation.
Stomach pain or cramps.
Bloating.
Enlarged breasts.
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.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, 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 emergency 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 lump, breast pain or soreness, 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, 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 immediate medical attention if you experience:
Signs of a blood clot: chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, changes in color, or pain in a leg or arm; or trouble speaking or swallowing.
Signs of high calcium levels (more common in people with cancer): weakness, confusion, fatigue, headache, upset stomach or vomiting, constipation, or bone pain.
Other Possible Side Effects
While many people may not experience side effects or only have mild ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Dizziness or headache.
Hair loss.
Upset stomach or vomiting.
Constipation.
Stomach pain or cramps.
Bloating.
Enlarged breasts.
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.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, 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 chest pain or shortness of breath (possible blood clot in lungs)
- Sudden severe headache, vision changes, slurred speech, weakness on one side of the body (possible stroke)
- Pain, swelling, or redness in one leg (possible deep vein thrombosis)
- Abnormal vaginal bleeding (e.g., bleeding after menopause, heavy or prolonged bleeding)
- Lump in the breast or nipple discharge
- Yellowing of the skin or eyes (jaundice)
- Severe abdominal pain
- Changes in mood, depression
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, such as:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack
+ Stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Pregnancy or potential pregnancy. Note: This medication is contraindicated during pregnancy and should not be taken if you are pregnant.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction and its symptoms.
A history of certain health conditions, such as:
+ Bleeding disorders
+ Blood clots or an increased risk of blood clots
+ Breast cancer
+ Liver problems or liver tumors
+ Heart attack
+ Stroke
+ Tumors that are sensitive to estrogen
Unexplained vaginal bleeding
Pregnancy or potential pregnancy. Note: This medication is contraindicated during pregnancy and should not be taken if you are pregnant.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your other medications and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor may advise you to stop taking this drug before certain surgical procedures, and will provide guidance on when to resume taking it after the surgery or procedure.
If you 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, it is crucial to closely monitor your blood sugar levels.
Regular blood pressure checks are necessary, as this medication can cause high blood pressure. Your doctor will also recommend regular blood tests and bone density checks to monitor your health.
It is vital to maintain regular breast exams and gynecology check-ups, and to perform breast self-exams as instructed by your doctor. The risk of certain side effects, such as heart attack, stroke, breast cancer, and ovarian cancer, may vary depending on factors like the duration of estrogen use, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor.
This medication may cause an increase in triglyceride levels, so inform your doctor if you have a history of high triglyceride levels. It 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 test results, so 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 discuss with your doctor if you regularly drink grapefruit juice or eat grapefruit.
In children and teenagers, this medication may affect growth in some cases, so regular growth checks may be necessary. Discuss this with your doctor. Before using other medications or skin products, including soaps, consult with your doctor. 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 inactivity may increase your risk of developing blood clots. Additionally, if you have diabetes, it is crucial to closely monitor your blood sugar levels.
Regular blood pressure checks are necessary, as this medication can cause high blood pressure. Your doctor will also recommend regular blood tests and bone density checks to monitor your health.
It is vital to maintain regular breast exams and gynecology check-ups, and to perform breast self-exams as instructed by your doctor. The risk of certain side effects, such as heart attack, stroke, breast cancer, and ovarian cancer, may vary depending on factors like the duration of estrogen use, whether it is taken with or without a progestin, and other individual factors. Discuss the benefits and risks of using this medication with your doctor.
This medication may cause an increase in triglyceride levels, so inform your doctor if you have a history of high triglyceride levels. It 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 test results, so 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 discuss with your doctor if you regularly drink grapefruit juice or eat grapefruit.
In children and teenagers, this medication may affect growth in some cases, so regular growth checks may be necessary. Discuss this with your doctor. Before using other medications or skin products, including soaps, consult with your doctor. 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; symptoms usually resolve upon discontinuation of the drug.
Drug Interactions
Major Interactions
- Aromatase inhibitors (e.g., anastrozole, letrozole, exemestane) - concurrent use would counteract their effect.
- Fulvestrant - concurrent use would counteract its effect.
- Tamoxifen - concurrent use would counteract its effect.
Moderate Interactions
- CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort) - may decrease estradiol levels, reducing efficacy.
- CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, 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.
- Corticosteroids (e.g., prednisone) - estrogens may decrease the clearance of corticosteroids, leading to increased effects.
- Anticoagulants (e.g., warfarin) - estrogens may affect coagulation parameters, requiring dose adjustment of anticoagulants.
Minor Interactions
- Lamotrigine - estrogens may decrease lamotrigine levels, potentially reducing seizure control.
Monitoring
Baseline Monitoring
Complete medical history and physical examination (including blood pressure, breast, and pelvic examination)
Rationale: To identify contraindications, risk factors for adverse events (e.g., VTE, breast cancer, cardiovascular disease), and establish baseline health status.
Timing: Prior to initiation of therapy
Lipid profile
Rationale: Estrogens can affect lipid metabolism; establish baseline.
Timing: Prior to initiation of therapy
Liver function tests (LFTs)
Rationale: Estrogens are metabolized by the liver; assess hepatic function.
Timing: Prior to initiation of therapy
Routine Monitoring
Annual physical examination (including blood pressure, breast, and pelvic examination)
Frequency: Annually
Target: Normal for age
Action Threshold: Any new or concerning findings (e.g., breast lump, abnormal bleeding, significant BP changes) require further investigation.
Mammography
Frequency: As clinically indicated, based on age and risk factors (typically annually or biennially)
Target: No suspicious findings
Action Threshold: Any suspicious findings require further diagnostic evaluation.
Endometrial monitoring (for women with intact uterus)
Frequency: If abnormal uterine bleeding occurs
Target: Normal endometrial thickness
Action Threshold: Persistent or recurrent abnormal bleeding requires endometrial biopsy to rule out malignancy.
Blood pressure
Frequency: Regularly (e.g., every 3-6 months)
Target: <130/80 mmHg
Action Threshold: Sustained elevation requires evaluation and management.
Symptom Monitoring
- Signs of blood clots (e.g., sudden chest pain, shortness of breath, pain/swelling in leg, sudden severe headache, vision changes)
- Signs of stroke (e.g., sudden numbness or weakness, confusion, trouble speaking, trouble walking, dizziness)
- Signs of heart attack (e.g., chest pain, discomfort in other areas of upper body, shortness of breath)
- Abnormal vaginal bleeding (e.g., spotting, bleeding after menopause)
- Breast lumps or changes
- Jaundice (yellowing of skin or eyes)
- Severe abdominal pain
- Mood changes, depression
Special Patient Groups
Pregnancy
Contraindicated in pregnancy. There is no indication for estrogen therapy in pregnancy. Estrogens may cause severe harm to the fetus, including genital abnormalities.
Trimester-Specific Risks:
First Trimester:
High risk of fetal harm, particularly genital abnormalities.
Second Trimester:
High risk of fetal harm.
Third Trimester:
High risk of fetal harm.
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 breastfed infant include feminization.
Infant Risk:
L4 (Possibly hazardous) - Potential for decreased milk production and excretion into breast milk with potential effects on infant.
Pediatric Use
Not indicated for pediatric use. Safety and efficacy have not been established in pediatric patients. Estrogen exposure in children can lead to premature puberty or other hormonal imbalances.
Geriatric Use
Use with caution in women 65 years of age or older. The WHI study showed an increased risk of probable dementia in women 65 years of age or older treated with CE alone or CE/MPA. Consider the lowest effective dose for the shortest duration. Increased risk of VTE and stroke may also be present in older women.
Clinical Information
Clinical Pearls
- Transdermal estradiol avoids first-pass hepatic metabolism, potentially leading to a more favorable lipid profile and lower risk of VTE compared to oral estrogens, though risks still exist.
- Ensure patients understand the proper application technique to maximize absorption and minimize transfer to others.
- 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, as HRT should be used for the shortest duration consistent with treatment goals.
- Counsel patients on the Black Box Warning regarding cardiovascular events, stroke, breast cancer, and dementia.
Alternative Therapies
- Other transdermal estrogens (e.g., estradiol patches, sprays)
- Oral estrogens (e.g., conjugated estrogens, oral estradiol)
- Vaginal estrogens (for localized symptoms only)
- Non-hormonal therapies for vasomotor symptoms (e.g., SSRIs/SNRIs like paroxetine, venlafaxine; gabapentin; clonidine)
- Lifestyle modifications (e.g., diet, exercise, stress reduction)
Cost & Coverage
Average Cost:
$100 - $200 per 37.5g pump (approx. 30 days supply)
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 it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about what was taken, the amount, and the time it occurred.