17 β Estradiol

• Treatment of moderate to severe vasomotor symptoms (hot flashes, night sweats) associated with menopause.
• Treatment of symptoms of estrogen deficiency such as vulvar and vaginal atrophy when systemic therapy is indicated.
• Prevention of osteoporosis in postmenopausal women at high risk of fracture who cannot use other treatments.
• Hormone replacement therapy for women with primary ovarian failure or hypogonadism.
• Off-label uses:
• Menopausal symptoms in women with surgical menopause.
• Feminizing hormone therapy in transgender women.

• Adults: Apply 1.5 g gel (approximately 1.5 mg estradiol) once daily to clean, dry, intact skin of inner forearms or shoulders. Avoid breasts or irritated skin. Allow to dry before dressing. Wash hands after application.
• Elderly: No specific dose adjustment; monitor closely.
• Pediatrics: Not indicated.
• Hepatic impairment: Use with caution due to altered metabolism.
• Renal impairment: Use cautiously; no specific dose adjustments defined.
• Missed dose should be applied as soon as possible without doubling the next dose.
• Use the lowest effective dose for the shortest duration consistent with treatment goals.

17β-Estradiol is a natural estrogen hormone that crosses cell membranes and binds to estrogen receptors (ERα and ERβ) inside the cell. The hormone-receptor complex then acts in the nucleus as a transcription factor to regulate genes responsible for female secondary sexual characteristics, relief of menopausal symptoms, and maintenance of bone density by inhibiting osteoclast-mediated bone resorption.

• Absorption: Transdermal route avoids first-pass metabolism, achieving stable plasma estradiol levels with peak concentration around 4–6 hours after application.
• Distribution: Extensive binding to sex hormone-binding globulin (SHBG) and albumin.
• Metabolism: Hepatic metabolism via CYP450 enzymes (primarily CYP3A4), hydroxylation, and conjugation.
• Excretion: Metabolites excreted in urine and feces.
• Half-life: Approximately 27–37 hours, enabling steady hormone levels.

• Pregnancy: FDA Category X. Contraindicated due to risk of fetal harm.
• Lactation: Estradiol is excreted in breast milk and may suppress lactation; use during breastfeeding is not recommended unless benefits outweigh risks. Data are limited, so caution is advised.

• Estrogen hormone replacement therapy
• Subclass: Transdermal estradiol preparation

• Known or suspected estrogen-dependent cancers (breast, endometrial).
• Undiagnosed abnormal vaginal bleeding.
• Active or history of venous thromboembolism (deep vein thrombosis, pulmonary embolism).
• Active or history of arterial thromboembolic disease (stroke, myocardial infarction).
• Severe liver disease.
• Pregnancy or breastfeeding.
• Hypersensitivity to estradiol or formulation components.

• Increased risk of endometrial hyperplasia and carcinoma if uterus is intact without concomitant progestogen.
• Elevated risk of thromboembolism and cardiovascular events; avoid in high-risk patients.
• Monitor for breast cancer with regular mammography.
• Use cautiously in patients with cardiovascular risk factors, hypertension, diabetes, or hyperlipidemia.
• Smoking increases thrombotic risk and should be discouraged.
• Early warning signs of serious adverse events include leg swelling/pain, chest pain, severe headache, or visual changes.

• Common: Local skin irritation, breast tenderness, headache, nausea.
• Serious but rare: Venous thromboembolism, stroke, myocardial infarction, gallbladder disease, breast and endometrial cancers.
• Side effects may be dose-dependent and onset can vary from weeks to months.

• CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s Wort) reduce estradiol levels, potentially lowering effectiveness.
• CYP3A4 inhibitors may increase estradiol levels, increasing side effect risk.
• Anticoagulants may have altered effects; monitor coagulation status.
• Alcohol may exacerbate hepatic effects.
• Smoking significantly increases thrombotic risk.

• Current guidelines recommend lowest effective dose for shortest duration.
• Transdermal estradiol preferred over oral in women at thromboembolic risk.
• Osteoporosis prevention use limited to women intolerant or contraindicated to other therapies.
• Stricter warnings for cardiovascular and thrombotic risks have been emphasized.

• Store at 20–25°C (68–77°F); excursions permitted between 15–30°C (59–86°F).
• Protect from light and moisture.
• Keep tube tightly closed when not in use.
• Do not freeze.
• Keep out of reach of children.
• No reconstitution needed.