Estradiol

Estradiol, also known as 17β-estradiol, is the most potent natural estrogen and the principal female sex hormone in premenopausal women. It is a steroid produced mainly by the ovarian granulosa cells, with contributions from the placenta during pregnancy and from peripheral aromatization of androgens in adipose tissue and other organs in both sexes.

Circulating estradiol is mostly bound to sex hormone-binding globulin and albumin; only a small fraction remains free to enter cells. Estradiol exerts its effects by binding estrogen receptors ERα and ERβ, regulating gene transcription and, in some tissues, triggering rapid signaling cascades.

Physiologically, estradiol supports development and maintenance of the female reproductive tract, regulates the menstrual cycle and ovulation, contributes to bone density and cardiovascular health, and influences secondary sexual characteristics, mood, and cognition.

Medical use includes hormone replacement therapy for menopausal symptoms and osteoporosis prevention, delivered by oral, transdermal, vaginal, or other routes. In individuals with a uterus, estrogens are typically combined with progestins to reduce the risk of endometrial cancer. Estradiol is also used in feminizing hormone therapy for transgender women and in certain assisted reproduction protocols.

Pharmacokinetics vary by route. Oral estradiol undergoes significant first-pass metabolism with relatively low bioavailability; transdermal and vaginal routes bypass first-pass metabolism. It is metabolized in the liver to estrone and estriol and excreted in urine and bile.

Safety considerations include an increased risk of venous thromboembolism, stroke, myocardial infarction, gallbladder disease, and breast tenderness with estrogen therapy. Unopposed estrogen increases endometrial cancer risk in women with an intact uterus. Contraindications include pregnancy, active thromboembolic disease, estrogen-dependent cancers, and certain liver or cardiovascular conditions.