What is Elestrin (estradiol)?

What is Elestrin?

Elestrin is a transdermal estradiol gel 0.1% that delivers estradiol through the skin for the treatment of moderate to severe vasomotor symptoms associated with menopause. 1

Composition and Formulation

• Elestrin contains 17β-estradiol, which is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol, at the receptor level 2
• It is formulated as a topical gel that delivers estradiol systemically when applied to the skin, bypassing first-pass hepatic metabolism 1
• Each gram of estradiol gel contains 0.1 mg of estradiol (0.01%) in a non-liquefying base 2

Mechanism of Action

• Estradiol acts through binding to nuclear receptors in estrogen-responsive tissues throughout the body 2
• Circulating estrogens modulate pituitary secretion of gonadotropins (LH and FSH) through negative feedback, reducing the elevated levels of these hormones seen in postmenopausal women 2
• Transdermal delivery allows for more stable systemic estradiol levels compared to oral administration 3

Pharmacokinetics

• Estradiol is absorbed through the skin after application of the gel 2
• Transdermal administration avoids first-pass hepatic metabolism, allowing for lower doses to achieve therapeutic effects 3
• Estradiol is widely distributed in the body with higher concentrations in sex hormone target organs 2
• It circulates largely bound to sex hormone binding globulin (SHBG) and albumin 2
• Metabolism occurs primarily in the liver, where estradiol is converted reversibly to estrone, and both can be converted to estriol 2

Clinical Uses

• Treatment of moderate to severe vasomotor symptoms (hot flashes) associated with menopause 1, 4
• Management of vulvar and vaginal atrophy symptoms in postmenopausal women 1
• Estrogen replacement therapy for women with premature ovarian insufficiency (POI) 5

Dosing Options

• Available in multiple dosing options to individualize patient therapy 1
• Doses typically range from 0.25 mg to 1.0 mg of estradiol gel daily, with estimated daily deliveries of 0.003 to 0.027 mg of estradiol 1
• The lowest available effective dose (0.25 mg estradiol, delivering 0.003 mg/d estradiol) can be used to treat vasomotor symptoms 1

Efficacy

• Provides significant reductions in frequency and severity of vasomotor symptoms as early as 2 weeks after initiation of treatment 1
• Effectively improves signs of vulvar and vaginal atrophy 1
• Comparative studies suggest that Elestrin (Divigel) 1.0 mg provides the best efficacy profile for hot flush reduction compared to other transdermal estradiol preparations 6

Safety Considerations

• Women with an intact uterus should receive a progestogen in combination with estradiol to protect the endometrium 5
• Generally contraindicated in breast cancer survivors 5
• May be an option for women carrying BRCA1/2 mutations without personal history of breast cancer after prophylactic bilateral salpingo-oophorectomy 5
• For women with endometriosis who required oophorectomy, combined estrogen/progestogen therapy can effectively treat vasomotor symptoms 5
• Migraine should not be considered a contraindication to hormone replacement therapy in women with POI 5

Advantages of Transdermal Estradiol

• Achieves physiological estradiol levels with lower daily doses compared to oral administration 7, 3
• Avoids first-pass hepatic metabolism, potentially resulting in fewer undesirable effects on hepatic metabolism 3
• Provides more stable plasma concentrations of estradiol 7
• May have a milder impact on coagulation, fibrinolysis markers, and lipid profile compared to synthetic estrogens like ethinyl estradiol 8
• Associated with lower risk of thromboembolic events compared to oral estrogen preparations 8

Common Side Effects

• Local skin reactions at the application site (typically mild) 4
• Breast pain 4
• Headache 4
• Potential endometrial thickening (if not used with progestogen in women with intact uterus) 4

Drug Interactions

• Medications that induce CYP3A4 (such as St. John's Wort, phenobarbital, carbamazepine, rifampin) may reduce plasma concentrations of estradiol 2
• Inhibitors of CYP3A4 (erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, grapefruit juice) may increase plasma concentrations of estradiol 2