I'm sometimes asked why estradiol is used by itself in menopausal hormone therapy even though there are 3 forms of estrogen - estrone (E1), estradiol (E2) and estriol (E3).
Estrone levels remain constant and do not decline with age. 1 This form of estrogen is made in fat cells through a process called aromatization. It’s higher in women who are obese and increases the risk of endometrial cancer.5
Estradiol is 12 times more potent than estrone and 80 times more potent than estriol.5 The safety and efficacy of bio-identical estradiol has been studied extensively. An analysis of 44 studies revealed that vaginal estradiol (E2) effectively improved symptoms of vaginal dryness, pain with intercourse, pain with urination, urinary urgency and frequency, recurrent bladder infections, urinary incontinence and physical exam findings. 2 Systemic estradiol (regardless of the route of administration - orally, topically or with a vaginal ring) has been shown to decrease hot flashes and night sweats, improve sleep and improve quality of life. 3
Estriol is made by the placenta during pregnancy.5 Estriol is currently not FDA-approved for the treatment of menopausal symptoms. A recent analysis of 6 separate studies showed that both vaginal estradiol (E2) and vaginal estriol (E3) were effective at alleviating vaginal symptoms of dryness, burning, itching, and pain with intercourse. 4 The most common side effect, although rare, was abnormal uterine bleeding.
Because the preponderance of research is on estradiol, most menopause practitioners use this to treat menopausal symptoms related to estrogen deficiency. When appropriate, the North American Menopause Society recommends that FDA-approved, evidence-based medications be prescribed by health care providers experienced in the treatment of menopausal symptoms. I understand some women will choose other options, and I'm grateful women have so many options. I feel estradiol is a well-researched first choice for women who need systemic or vaginal estrogen therapy.
1. Emmerson E, Hardman MJ. The role of estrogen deficiency in skin ageing and wound healing. Biogerontology 2012;13(1):3–20.
2. Rahn DD, Carberry C, Sanses TV, et al. Vaginal estrogen for genitourinary syndrome of menopause: a systematic review. Obstet Gynecol 2014;124(6):1147–56.
3. Archer DF, Bernick BA, Mirkin S. A combined, bioidentical, oral, 17β-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause. Expert Rev Clin Pharmacol 2019;12(8):729–39.
4. Biehl C, Plotsker O, Mirkin S. A systematic review of the efficacy and safety of vaginal estrogen products for the treatment of genitourinary syndrome of menopause. Menopause 2019;26(4):431–53.
5. The Estrogen Window, Mache Seibel