Estradiol

HRT MEMBERS ONLY

INDICATIONS FOR USE

Estradiol is used in hormone replacement therapy (HRT) for postmenopausal women to treat vasomotor symptoms, vaginal atrophy, and osteoporosis prevention. It may also be used for hypoestrogenism due to primary ovarian insufficiency.

ROUTE OF ADMINISTRATION

  • Topical gel, cream, or transdermal patch.

COMMON INITIAL DOSING REGIMENS

  • Topical Gel/Cream: Typically 0.5–1.5 mg applied once daily to the inner thighs or arms.

  • Transdermal Patch: 0.025–0.1 mg estradiol released daily, replaced once or twice weekly.

MECHANISM OF ACTION

  • Estradiol binds to estrogen receptors, regulating gene expression and mimicking endogenous estrogen effects. It alleviates menopausal symptoms by maintaining vaginal epithelium, reducing hot flashes, and supporting bone density.

COMMON SIDE EFFECTS

  • Endocrine: Breast tenderness, increased vaginal discharge, or breakthrough bleeding.

  • Metabolic: Fluid retention, weight changes, or mild bloating.

  • Cardiovascular: Rare risks include venous thromboembolism (VTE) and hypertension.

  • Dermatological: Local skin irritation with transdermal patches.

  • Rare: Long-term use may increase risks of endometrial hyperplasia or estrogen-dependent cancers.

CONTRAINDICATIONS

  • Absolute: Active or history of estrogen-dependent cancer, thromboembolic disorders, or undiagnosed vaginal bleeding.

  • Relative: Caution in women with liver dysfunction, gallbladder disease, or significant cardiovascular risk factors.

MORE INFORMATION

  • FDA Safety Data Sheet can be found here

  • Tang Y. Effectiveness and safety of hormone replacement therapy in the treatment of menopausal syndrome: a meta-analysis. Am J Transl Res. 2025 [PubMed Link]

  • Wang L. Hormone therapy with different administration routes for patients with perimenopausal syndrome: a systematic review and network meta-analysis. Gynecol Endocrinol. 2025 [PubMed Link]

  • Lu DH. Association between hormone replacement therapy and sex hormones in postmenopausal women: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2023 [PubMed Link]

  • Hevener AL. Metabolic Messengers: Estradiol. Nat Metab. 2025 [PubMed Link]

  • Yang Z. Estradiol therapy and breast cancer risk in perimenopausal and postmenopausal women: a systematic review and meta-analysis. Gynecol Endocrinol. 2017 [PubMed Link]

  • Cucinella L. Sexual function after menopause: the role of vaginal estrogens. Maturitas. 2025 [PubMed Link]

  • Ali A. Efficacy and Safety of Intravaginal Estrogen in the Treatment of Atrophic Vaginitis: A Systematic Review and Meta-Analysis. J Menopausal Med. 2024 [PubMed Link]

  • Whedon JM. Bioidentical Estrogen for Menopausal Depressive Symptoms: A Systematic Review and Meta-Analysis. J Womens Health (Larchmt). 2017 [PubMed Link]

  • Burgos N. Estrogen-based hormone therapy in women with primary ovarian insufficiency: a systematic review. Endocrine. 2017 [PubMed Link]

  • Pan Z. Different regimens of menopausal hormone therapy for improving sleep quality: a systematic review and meta-analysis. Menopause. 2022 [PubMed Link]