Due to its estrogenic activity, estradiol has antigonadotropic effects and can inhibit fertility and suppress sex hormone production in both women and men. Estradiol differs from non-bioidentical estrogens like conjugated estrogens and ethinylestradiol in various ways, with implications for tolerability and safety.Estradiol was discovered in 1933. It became available as a medication that same year, in an injectable form known as estradiol benzoate. Forms that were more useful by mouth, estradiol valerate and micronized estradiol, were introduced in the 1960s and 1970s and increased its popularity by this route. Estradiol is also used as other prodrugs, like estradiol cypionate. Related estrogens such as ethinylestradiol, which is the most common estrogen in birth control pills, and conjugated estrogens (brand name Premarin), which is used in menopausal hormone therapy, are used as medications as well. In 2020, it was the 59th most commonly prescribed medication in the United States, with more than 11 million prescriptions. Medical uses
Hormone therapy
Menopause
Estradiol is used in menopausal hormone therapy to prevent and treat moderate to severe menopausal symptoms such as hot flashes, vaginal dryness and atrophy, and osteoporosis (bone loss). As unopposed estrogen therapy (using estrogen alone without progesterone) increases the risk of endometrial hyperplasia and endometrial cancer in women with intact uteruses, estradiol is usually combined with a progestogen like progesterone or medroxyprogesterone acetate to prevent the effects of estradiol on the endometrium. This is not necessary if the woman has undergone a hysterectomy (surgical removal of the uterus).
Older age, higher body weight, lower physical activity, and smoking are all associated with a higher risk of VTE with oral estrogen therapy. Risk of VTE with estrogen therapy is highest at the start of treatment, particularly during the first year, and decreases over time.The absolute risk of VTE with estrogen and/or progestin therapy is small. Women who are not on a birth control pill or hormone therapy have a risk of VTE of about 1 to 5 out of 10,000 women per year. In women taking a birth control pill containing ethinylestradiol and a progestin, the risk of VTE is in the range of 3 to 10 out of 10,000 women per year. Birth control pills containing estradiol valerate and a progestin are associated with about half the risk of VTE of ethinylestradiol/progestin-containing birth control pills. Hormone therapy for transgender women likewise is associated with a lower risk of VTE than birth control pills containing ethinylestradiol and a progestin. The risk of VTE during pregnancy, when estrogens and progesterone increase to very high levels, is 5 to 20 in 10,000 women per year, while the risk is 40 to 65 per 10,000 women per year during the postpartum period. Long-term effects
Uncommon but serious possible side effects of estrogens associated with long-term therapy may include breast cancer, uterine cancer, stroke, heart attack, blood clots, dementia, gallbladder disease, and ovarian cancer.