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Estradiol: From Swing to Shift
April 21, 2026
Watch Belmar Pharma Solutions Medical Director, Angela DeRosa, DO, MBA, CPE, and Clinical Director of Women’s Health, Andi Roths, PharmD, […]
Estradiol (E2)
Estradiol is the strongest and most active of the three primary estrogens and may have a role in supporting menstrual, bone, cardiovascular, and overall cellular health.
Common dosage forms
Capsule
Cream
Fast SL
Gel
Ointment
Oral Tablet
Pellets
Solution
Suspension
Suppository
Troche
Vaginal Tablet
What is Estradiol?
Estradiol (E2) is the strongest and most active of the three primary estrogens and is produced mainly by the ovaries before menopause, with smaller amounts made by the adrenal glands and fat tissue. It accounts for 5–10% of circulating estrogen and binds most effectively to estrogen receptors, allowing it to influence a wide range of biological functions in cells throughout the body.
Estradiol may play an essential role in the menstrual cycle, reproductive health, bone density, skin integrity, temperature regulation, and cardiovascular and neurological function. It also may participate in feedback control of luteinizing hormone and follicle-stimulating hormone, helping maintain hormonal balance across the endocrine system.
Men and women both produce estradiol, though men generate smaller amounts through the conversion of testosterone. Because estradiol supports vaginal tissue health, bone maintenance, and thermoregulation, it may be prescribed when natural estrogen levels decline. In clinical practice, estradiol is prepared in several compounded forms—including estradiol vaginal cream, estradiol cream, and estradiol tablets—to accommodate different needs and delivery preferences.
Who May Benefit from Estradiol Therapy?
Postmenopausal women with low estrogen symptoms
Women experiencing hot flashes, night sweats, or vaginal dryness after menopause may benefit from estradiol therapy, which may help restore declining estrogen levels. Forms such as estradiol vaginal cream, estradiol cream, or estradiol tablets can support vaginal comfort, temperature regulation, and overall quality of life.
Bone density concerns
Estradiol may help slow bone loss by supporting calcium absorption and maintaining bone strength. Adults at increased risk for weak or fragile bones may benefit from estradiol therapy, including options like estradiol tablets when systemic support is needed.
Vaginal or urogenital discomfort
Estradiol may support the thickness, flexibility, and lubrication of vaginal tissues, which often decline when estrogen levels drop. Those with dryness, irritation, or narrowing of the vaginal canal may benefit from localized therapies such as estradiol vaginal cream or estradiol cream.
Estrogen deficiency
Those with naturally low estrogen levels due to aging, surgery, or certain medical conditions may benefit from estradiol to help restore hormonal balance. Depending on the need, estradiol may be provided through estradiol tablets or topical forms like estradiol cream.
What are bioidentical hormones?
Bioidentical hormones, predominantly isolated from plant materials, have the exact chemical and molecular structure as hormones made in the human body. Bioidentical steroid hormones like estradiol are designed to bind to the same receptors and undergo similar enzymatic breakdown. Dose and delivery route are essential to activity, which is why compounded bioidentical hormone replacement therapy (BHRT) offers distinctive options that maximize therapeutic use.
Access clinical studies on Estradiol
- Britto R, Araújo L, Barbosa I, Silva L. Improvement of the lipid profile in post menopausal women who use estradiol and testosterone implants. Gynecological Endocrinology, 2012; 28(10):767-769.
- Klein DA, Paradise SL, Goodwin ET. Caring for Transgender and Gender-Diverse Persons: What Clinicians Should Know. Am Fam Physician. 2018 Dec 1;98(11):645-653.
- Irving A, Lehault WB. Clinical pearls of gender-affirming hormone therapy in transgender patients. Ment Health Clin. 2018 Mar 26;7(4):164-167.
- Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T’Sjoen GG. Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017 Nov 1;102(11):3869-3903.
- Hashemi L, Weinreb J, Weimer AK, Weiss RL. Transgender Care in the Primary Care Setting: A Review of Guidelines and Literature. Fed Pract. 2018 Jul;35(7):30-37.
- Awouters M, Vanderschueren D, Antonio L. Aromatase inhibitors and selective estrogen receptor modulators: Unconventional therapies for functional hypogonadism? Andrology. 2020 Nov;8(6):1590-1597.
- Mauvais-Jarvis F, Lindsey SH. Metabolic benefits afforded by estradiol and testosterone in both sexes: clinical considerations. J Clin Invest. 2024 Sep 3;134(17):e180073.
- Borozan S, Kamrul-Hasan ABM, Pappachan JM. Hormone replacement therapy for menopausal mood swings and sleep quality: The current evidence. World J Psychiatry. 2024 Oct 19;14(10):1605-1610.
- Lephart ED, Naftolin F. Menopause and the Skin: Old Favorites and New Innovations in Cosmeceuticals for Estrogen-Deficient Skin. Dermatol Ther (Heidelb). 2021 Feb;11(1):53-69. doi: 10.1007/s13555-020-00468-7. Epub 2020 Nov 26. PMID: 33242128; PMCID: PMC7859014.
- Kamp E, Ashraf M, Musbahi E, DeGiovanni C. Menopause, skin and common dermatoses. Part 1: hair disorders. Clin Exp Dermatol. 2022 Dec;47(12):2110-2116. doi: 10.1111/ced.15327. Epub 2022 Oct 28.
- Samaras N, Papadopoulou MA, Samaras D, Ongaro F. Off-label use of hormones as an antiaging strategy: a review. Clin Interv Aging. 2014 Jul 23;9:1175-86.
- Comhaire F. Hormone replacement therapy and longevity. Andrologia, 2016; 48(1):65-8.
- Zhang J, Yin J, Song X, Lai S, Zhong S, Jia Y. The effect of exogenous estrogen on depressive mood in women: A systematic review and meta-analysis of randomized controlled trials. J Psychiatr Res. 2023 Jun;162:21-29.
- Mosconi L, Nerattini M, Matthews DC, Jett S, Andy C, Williams S, Yepez CB, Zarate C, Carlton C, Fauci F, Ajila T, Pahlajani S, Andrews R, Pupi A, Ballon D, Kelly J, Osborne JR, Nehmeh S, Fink M, Berti V, Dyke JP, Brinton RD. In vivo brain estrogen receptor density by neuroendocrine aging and relationships with cognition and symptomatology. Sci Rep. 2024 Jun 20;14(1):12680.
- Holroyd CR, Edwards CJ. The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus. Climacteric. 2009 Oct;12(5):378-86.
- Schwartz E, Morelli V, Holtorf K. Hormone replacement therapy in the geriatric patient: current state of the evidence and questions for the future–estrogen, progesterone, testosterone, and thyroid hormone augmentation in geriatric clinical practice: part 2. Clin Geriatr Med. 2011 Nov;27(4):561-75. doi: 10.1016/j.cger.2011.07.004. PMID: 22062441.
- Wang J, Wang L. The therapeutic effect of dehydroepiandrosterone (DHEA) on vulvovaginal atrophy. Pharmacol Res. 2021 Apr;166:105509
- Loflin BJ, Westmoreland K, Williams NT. Vulvodynia: A Review of the Literature. J Pharm Technol. 2019 Feb;35(1):11-24.
- Goldstein I, Alexander JL. Practical aspects in the management of vaginal atrophy and sexual dysfunction in perimenopausal and postmenopausal women. J Sex Med. 2005 Sep;2 Suppl 3:154-65.
- Hurtado MD, Tama E, Fansa S, Ghusn W, Anazco D, Acosta A, Faubion SS, Shufelt CL. Weight loss response to semaglutide in postmenopausal women with and without hormone therapy use. Menopause. 2024 Apr 1;31(4):266-274. doi: 10.1097/GME.0000000000002310.
- Santoro N, Roeca C, Peters BA, Neal-Perry G. The Menopause Transition: Signs, Symptoms, and Management Options. J Clin Endocrinol Metab. 2021 Jan 1;106(1):1-15.
- Santoro N. Perimenopause: From Research to Practice. J Womens Health (Larchmt). 2016 Apr;25(4):332-9. doi: 10.1089/jwh.2015.5556.
- Marlatt KL, Pitynski-Miller DR, Gavin KM, Moreau KL, Melanson EL, Santoro N, Kohrt WM. Body composition and cardiometabolic health across the menopause transition. Obesity (Silver Spring). 2022 Jan;30(1):14-27.
- Maki PM, Jaff NG. Brain fog in menopause: a health-care professional’s guide for decision-making and counseling on cognition. Climacteric. 2022 Dec;25(6):570-578.
- Kim YJ, Soto M, Branigan GL, Rodgers K, Brinton RD. Association between menopausal hormone therapy and risk of neurodegenerative diseases: Implications for precision hormone therapy. Alzheimers Dement (N Y). 2021 May 13;7(1):e12174.
- Gava G, Orsili I, Alvisi S, Mancini I, Seracchioli R, Meriggiola MC. Cognition, Mood and Sleep in Menopausal Transition: The Role of Menopause Hormone Therapy. Medicina (Kaunas). 2019 Oct 1;55(10):668.
- Vincent C, Bodnaruc AM, Prud’homme D, Olson V, Giroux I. Associations between menopause and body image: A systematic review. Womens Health (Lond). 2023 Jan-Dec;19:17455057231209536.
- Sochocka M, Karska J, Pszczołowska M, Ochnik M, Fułek M, Fułek K, Kurpas D, Chojdak-Łukasiewicz J, Rosner-Tenerowicz A, Leszek J. Cognitive Decline in Early and Premature Menopause. Int J Mol Sci. 2023 Mar 31;24(7):6566. doi: 10.3390/ijms24076566.
- Scheyer O, Rahman A, Hristov H, Berkowitz C, Isaacson RS, Diaz Brinton R, Mosconi L. Female Sex and Alzheimer’s Risk: The Menopause Connection. J Prev Alzheimers Dis. 2018;5(4):225-230. doi: 10.14283/jpad.2018.34.
- Ruiz AD, Daniels KR, Barner JC, Carson JJ, Frei CR. Effectiveness of compounded bioidentical hormone replacement therapy: an observational cohort study. BMC Womens Health. 2011 Jun 8;11:27.
- Gandhi J, Chen A, Dagur G, Suh Y, Smith N, Cali B, Khan SA. Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol. 2016 Dec;215(6):704-711.
- Faubion SS, Sood R, Kapoor E. Genitourinary Syndrome of Menopause: Management Strategies for the Clinician. Mayo Clin Proc. 2017 Dec;92(12):1842-1849.
Access package inserts for Estradiol
Commonly Asked Questions
Estradiol vaginal cream may be used to support vaginal tissue health in women with low estrogen levels, helping improve moisture, elasticity, and overall comfort. It may be recommended for symptoms such as vaginal dryness or discomfort that can occur after menopause.
Estradiol may contribute to side effects such as bloating or weight gain when used without progesterone or when hormone levels are not well balanced. These effects may improve once dosing, formulation, or hormone balance is adjusted under professional guidance.
Estradiol is one specific type of estrogen, and it is the most potent and biologically active of the three primary estrogens made in the body. While estradiol is a form of estrogen, the term estrogen refers to a broader group of hormones that also includes estrone (E1) and estriol (E3).
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