|This article needs additional citations for verification. (February 2013)|
|Systematic (IUPAC) name|
|Trade names||Climara, Menostar|
|Bioavailability||97–99% is bound|
|Excretion||Urine and sweat glands|
|(what is this?)|
Estradiol, or more precisely, 17β-estradiol, is a human sex hormone and steroid, and the primary female sex hormone. It is named for and is important in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is essential for the development and maintenance of female reproductive tissues but it also has important effects in many other tissues including bone. While estrogen levels in men are lower compared to women, estrogens have essential functions in men as well. Estradiol is found in most vertebrates as well as many crustaceans, insects, fish, and other animal species.
Estradiol or oestradiol (American or British English usages), derives from estra-, Gk. οἶστρος (oistros, literally meaning "verve or inspiration") and -diol, a chemical name and suffix indicating that this form of steroid and sex hormone is a type of alcohol bearing two hydroxyl groups.
Estradiol is produced especially within the follicles of female ovaries, but also in other endocrine (i.e., hormone-producing) and non-endocrine tissues (e.g., including fat, liver, adrenal, breast, and neural tissues). Estradiol is biosynthesized from progesterone (arrived at in two steps from cholesterol, via intermediate pregnenolone). One principle pathway then converts progesterone to its 17-hydroxy-derivative, and then to androstenedione via sequential cytochrome P450-catalyzed oxidations. Action of aromatase on this dione generates estrone, and action of a dehydrogenase on this gives the title compound, 17β-estradiol.
- 1 Effects
- 2 Medical uses
- 3 Estradiol medications
- 4 Adverse effects
- 5 Biosynthesis and localization
- 6 Mechanism of action
- 7 Metabolism
- 8 Levels and potency of estrogens
- 9 Measurement
- 10 See also
- 11 References
- 12 External links
- 13 Additional images
In the female, estradiol acts as a growth hormone for tissue of the reproductive organs, supporting the lining of the vagina, the cervical glands, the endometrium, and the lining of the fallopian tubes. It enhances growth of the myometrium. Estradiol appears necessary to maintain oocytes in the ovary. During the menstrual cycle, estradiol produced by the growing follicle triggers, via a positive feedback system, the hypothalamic-pituitary events that lead to the luteinizing hormone surge, inducing ovulation. In the luteal phase, estradiol, in conjunction with progesterone, prepares the endometrium for implantation. During pregnancy, estradiol increases due to placental production. In baboons, blocking of estrogen production leads to pregnancy loss, suggesting estradiol has a role in the maintenance of pregnancy. Research is investigating the role of estrogens in the process of initiation of labor. Actions of estradiol are required before the exposure of progesterone in the luteal phase.
The development of secondary sex characteristics in women is driven by estrogens, to be specific, estradiol. These changes are initiated at the time of puberty, most are enhanced during the reproductive years, and become less pronounced with declining estradiol support after the menopause. Thus, estradiol enhances breast development, and is responsible for changes in the body shape, affecting bones, joints and fat deposition. Fat structure and skin composition are modified by estradiol.
The effect of estradiol (and estrogens) upon male reproduction is complex. Estradiol is produced by action of aromatase mainly in the Leydig cells of the mammalian testis, but also by some germ cells and the Sertoli cells of immature mammals. It functions (in vitro) to prevent apoptosis of male sperm cells.
Several studies have noted sperm counts have been declining in many parts of the world, and estrogen exposure in the environment has been postulated to be the cause. Suppression of estradiol production in a subpopulation of subfertile men may improve the semen analysis.
Estradiol has a profound effect on bone. Individuals without it (or other estrogens) will become tall and eunuchoid, as epiphyseal closure is delayed or may not take place. Bone structure is affected also, resulting in early osteopenia and osteoporosis. Also, women past menopause experience an accelerated loss of bone mass due to a relative estrogen deficiency.
Estradiol has complex effects on the liver. It can lead to cholestasis. It affects the production of multiple proteins, including lipoproteins, binding proteins, and proteins responsible for blood clotting.
The positive and negative feedback loops of the menstrual cycle involve ovarian estradiol as the link to the hypothalamic-pituitary system to regulate gonadotropins. (See Hypothalamic–pituitary–gonadal axis.)
Estrogen is considered to play a significant role in women’s mental health, with links suggested between the hormone level, mood and well-being. Sudden drops or fluctuations in, or long periods of sustained low levels of estrogen may be correlated with significant mood-lowering. Clinical recovery from depression postpartum, perimenopause, and postmenopause was shown to be effective after levels of estrogen were stabilized and/or restored.
Recently, the volumes of sexually dimorphic brain structures in phenotypical males were found to change and approximate typical female brain structures when exposed to estradiol over a period of months, suggesting estradiol has a significant part to play in sex differentiation of the brain, both prenatally and throughout life.
There is also evidence the programming of adult male sexual behavior in many vertebrates is largely dependent on estradiol produced during prenatal life and early infancy. It is not yet known whether this process plays a significant role in human sexual behavior, although evidence from other mammals tends to indicate a connection.
Estrogen is suspected to activate certain oncogenes, as it supports certain cancers, notably breast cancer and cancer of the uterine lining. In addition, several benign gynecologic conditions are dependent on estrogen, such as endometriosis, leiomyomata uteri, and uterine bleeding.
The effect of estradiol, together with estrone and estriol, in pregnancy is less clear. They may promote uterine blood flow, myometrial growth, stimulate breast growth and at term, promote cervical softening and expression of myometrial oxytocin receptors.
A chemical derivative of estradiol, ethinyl estradiol with maximum dosage 200 µg, is a major component of hormonal contraceptive devices. Combined forms of hormonal contraception contain ethinyl estradiol and a progestin, which both contribute to the inhibition of GnRH, LH, and FSH, which accounts for the ability of these birth control methods to prevent ovulation and thus prevent pregnancy. Other types of hormonal birth control contain only progestins and no ethinyl estradiol.
Hormone replacement therapy
If severe side effects of low levels of estradiol in a woman's blood are experienced (commonly at the beginning of menopause or after oophorectomy), hormone replacement therapy may be prescribed. Such therapy is usually combined with a progestin to reduce the risk of endometrial cancer.
Estrogen therapy may be used in treatment of infertility in women when there is a need to develop sperm-friendly cervical mucus or an appropriate uterine lining. This is often prescribed in combination with clomifene.
Not all products are available worldwide. Estradiol is also part of conjugated estrogen preparations, such as Premarin, though it is not the major ingredient. (Premarin consists of a large number of estrogen derivatives. As the name indicates, it comes from pregnant mares' urine.)
Hormone replacement therapy in transgender women
Estrogen therapy is also used as part of the hormone replacement therapy for trans women. Either oral or transdermal estradiol is used in higher concentrations during initial treatment and transition; estradiol is continued in lower doses to maintain female-level hormones following gender reassignment surgery.
Inducing a state of hypoestrogenism may be beneficial in certain situations where estrogens are contributing to unwanted effects, e.g., certain forms of breast cancer, gynecomastia, premature closure of epiphyses, and inhibiting feminization in female-to-male transsexual hormone treatment. Estrogen levels can be reduced by inhibiting production using gonadotropin-releasing factor agonists (GnRH agonists) or blocking the aromatase enzyme using an aromatase inhibitor, such as anastrozole, or with an estrogen receptor antagonist, such as tamoxifen.
Estrogen is marketed in a number of ways to address issues of hypoestrogenism. Thus, there are oral, transdermal, topical, injectable, and vaginal preparations. Furthermore, the estradiol molecule may be linked to an alkyl group at C17 (sometimes also at C3) position to facilitate the administration. Such modifications give rise to estradiol acetate (oral and vaginal applications) and to estradiol cypionate (injectable).
Oral preparations are not necessarily predictably absorbed, and are subject to a first pass through the liver, where they can be metabolized, and also initiate unwanted side effects. Therefore, alternative routes of administration that bypass the liver before primary target organs are hit have been developed. Transdermal and transvaginal routes are not subject to the initial liver passage.
List of estradiol medications
- Gel: Estrogel, Estrasorb, Estraderm
- Oral versions: estradiol (Estrace), estradiol hemihydrate (Estrofem), estradiol acetate (Femtrace), estradiol valerate (Estrofem, Progynova)
- Transdermal patches: Alora, Climara, Minivelle, Vivelle-Dot, Menostar, Estraderm
- Topical Spray: EvaMist
- Ointments: Divigel, Estrasorb Topical, Elestrin
- Injection: estradiol benzoate, estradiol cypionate, estradiol valerate
- Vaginal ointment: Estrace Vaginal Cream
- Vaginal ring: Estring (estradiol), Femring (estradiol acetate)
- Vaginal tablet: Vagifem (estradiol hemihydrate)
- Estradiol combined with a progestin: CombiPatch (transdermal), Activella (oral), AngeliQ (oral)
Estradiol hemihydrate (INN; brand names Climara, Estraderm, Estralis, Estrasorb, Estreva, Estring, Estrofem, Estrogel, Vagifem, many others), or oestradiol hemihydrate, is the hemihydrate form of estradiol. In terms of activity and bioequivalence, estradiol and its hemihydrate are identical, with the only disparities being an approximate 1% difference in potency by weight (due to the presence of water molecules in the hemihydrate form of the substance) and a slower rate of release with certain formulations of the hemihydrate. This is because estradiol hemihydrate is more hydrated than anhydrous estradiol, and for that reason, is highly insoluble in water in comparison, which results in slower absorption rates with specific formulations such as Vagifem, a vaginal tablet form of the drug. Estradiol hemihydrate has also been shown to result in less systemic absorption as a vaginal tablet formulation relative to other topical estradiol formulations such as vaginal creams.
Adverse effects, which may occur as a result of use of estradiol and have been associated with estrogen and/or progestin therapy, include changes in vaginal bleeding, dysmenorrhea, increase in size of uterine leiomyomata, vaginitis including vaginal candidiasis, changes in cervical secretion and cervical ectropion, ovarian cancer, endometrial hyperplasia, endometrial cancer, nipple discharge, galactorrhea, fibrocystic breast changes and breast cancer. Cardiovascular effects include chest pain, deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke, and increased blood pressure. Gastrointestinal effects include nausea and vomiting, abdominal cramps, bloating, diarrhea, dyspepsia, dysuria, gastritis, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, or enlargement of hepatic hemangiomas. Skin adverse effects include chloasma or melasma that may continue despite discontinuation of the drug. Other effects on the skin include erythema multiforme, erythema nodosum, otitis media, hemorrhagic eruption, loss of scalp hair, hirsutism, pruritus, or rash. Adverse effects on the eyes include retinal vascular thrombosis, steepening of corneal curvature or intolerance to contact lenses. Adverse central nervous system effects include headache, migraine, dizziness, mental depression, chorea, nervousness/anxiety, mood disturbances, irritability, and worsening of epilepsy. Other adverse effects include changes in weight, reduced carbohydrate tolerance, worsening of porphyria, edema, arthralgias, bronchitis, leg cramps, hemorrhoids, changes in libido, urticaria, angioedema, anaphylactic reactions, syncope, toothache, tooth disorder, urinary incontinence, hypocalcemia, exacerbation of asthma, and increased triglycerides.
Estrogen combined with medroxyprogesterone acetate is associated with an increased risk of dementia. It is not known whether estradiol taken alone is associated with an increased risk of dementia. Estrogens should only be used for the shortest possible time and at the lowest effective dose due to these risks. Attempts to gradually reduce the medication via a dose taper should be made every three to six months.
Estradiol has been tied to the development and progression of cancers such as breast cancer, ovarian cancer and endometrial cancer. Estradiol effects target tissues by interacting with two nuclear hormone receptors called estrogen receptor α (ERα) and estrogen receptor β (ERβ). One of the functions of these estrogen receptors is gene expression. Once the hormone binds to the estrogen receptors, the hormone-receptor complexes then bind to specific DNA sequences, possibly causing damage to the DNA and an increase in cell division and DNA replication. Eukaryotic cells respond to damaged DNA by stimulating or impairing G1, S, or G2 phases of the cell cycle to initiate DNA repair. As a result, cellular transformation and cancer cell proliferation occurs.
St John's wort, phenobarbital, carbamazepine and rifampicin decrease the levels of estrogens, such as estradiol, by speeding up its metabolism, whereas erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may slow down metabolism, leading to increased levels in the blood plasma.
Estradiol should be avoided when there is undiagnosed abnormal genital bleeding, known, suspected or a history of breast cancer, current treatment for metastatic disease, known or suspected estrogen-dependent neoplasia, deep vein thrombosis, pulmonary embolism or history of these conditions, active or recent arterial thromboembolic disease such as stroke, myocardial infarction, liver dysfunction or disease. Estradiol should not be taken by people with a hypersensitivity/allergy or those who are pregnant or are suspected pregnant.
Biosynthesis and localization
|This section needs additional citations for verification. (June 2014)|
Estradiol, like other steroids, is derived from cholesterol. After side chain cleavage and using the delta-5 or the delta-4 pathway, androstenedione is the key intermediary. A fraction of the androstenedione is converted to testosterone, which in turn undergoes conversion to estradiol by an enzyme called aromatase. In an alternative pathway, androstenedione is aromatized to estrone, which is subsequently converted to estradiol.
During the reproductive years, most estradiol in women is produced by the granulosa cells of the ovaries by the aromatization of androstenedione (produced in the theca folliculi cells) to estrone, followed by conversion of estrone to estradiol by 17β-hydroxysteroid dehydrogenase. Smaller amounts of estradiol are also produced by the adrenal cortex, and (in men), by the testes.
Estradiol is not produced in the gonads only, in particular, fat cells produce active precursors to estradiol, and will continue to do so even after menopause. Estradiol is also produced in the brain and in arterial walls, though it cannot be readily transferred from the circulatory system into the brain. However, as one of the two active metabolites of testosterone in males (the other being dihydrotestosterone), it can be produced from this hormone within the brain.
Mechanism of action
Estradiol acts primarily as an agonist of the estrogen receptor (ER), a nuclear steroid hormone receptor. There are two subtypes of the ER, ERα and ERβ, and estradiol potently binds to and activates both of these receptors. The result of ER activation is a modulation of gene transcription and expression in ER-expressing cells, which is the predominant mechanism by which estradiol mediates its biological effects in the body. Estradiol also acts as an agonist of the intracellular membrane receptor GPER, a recently discovered non-nuclear estrogen receptor, through which it can mediate a variety of rapid, non-genomic effects. Unlike the case of the ER, GPER appears to be selective for estradiol, and shows very low affinities for other endogenous estrogens, such as estrone and estriol.
In the E2 classical pathway or estrogen classical pathway, estradiol enters the cytoplasm, where it causes dissociation of heat-shock protein (HSP). Estradiol now binds to HSP and can homodimerise (form structures of two HSP and two estradiol molecules) and then bind to specific domains on the nucleus (estrogen response element, ERE), allowing for gene transcription which can take place over hours and days.
In plasma, estradiol is largely bound to sex hormone-binding globulin, also to albumin. Only a fraction of 2.21% (± 0.04%) is free and biologically active, the percentage remaining constant throughout the menstrual cycle. Deactivation includes conversion to less-active estrogens, such as estrone and estriol. Estriol is the major urinary metabolite. Estradiol is conjugated in the liver by sulfate and glucuronide formation and, as such, excreted via the kidneys. Some of the water-soluble conjugates are excreted via the bile duct, and partly reabsorbed after hydrolysis from the intestinal tract. This enterohepatic circulation contributes to maintaining estradiol levels.
In the liver, estradiol is non-specifically metabolized by CYP1A2, CYP3A4, and CYP2C9 via 2-hydroxylation into 2-hydroxyestradiol, and by CYP2C9, CYP2C19, and CYP2C8 via 17β-hydroxy dehydrogenation into estrone, with various other cytochrome P450 (CYP) enzymes and metabolic transformations also being involved. As a result, cimetidine, a known, non-selective inhibitor of CYP450 enzymes, can increase the levels of exogenous, orally-ingested estradiol.
Levels and potency of estrogens
As the name implies, estradiol, sometimes abbreviated E2, has two hydroxyl groups in its molecular structure; its relatives estrone (E1) and estriol (E3) have one and three, respectively. Based on its unique chemical structure, estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect. During the reproductive years of the human female, its serum levels are somewhat higher than that of estrone, except during the early follicular phase of the menstrual cycle; thus, estradiol may be considered the predominant estrogen during human female reproductive years in terms of absolute serum levels and estrogenic activity. During pregnancy estriol becomes the predominant circulating estrogen, while during menopause, estrone predominates (both based on serum levels). The estradiol produced by male humans, from testosterone, is present at serum levels roughly comparable to postmenopausal women (14-55 versus <35 pg/mL, respectively).
In women, serum estradiol is measured in a clinical laboratory and reflects primarily the activity of the ovaries. As such, they are useful in the detection of baseline estrogen in women with amenorrhea or menstrual dysfunction, and to detect the state of hypoestrogenicity and menopause. Furthermore, estrogen monitoring during fertility therapy assesses follicular growth and is useful in monitoring the treatment. Estrogen-producing tumors will demonstrate persistent high levels of estradiol and other estrogens. In precocious puberty, estradiol levels are inappropriately increased.
Individual laboratory results should always been interpreted using the ranges provided by the laboratory that performed the test.
|Reference ranges for serum estradiol|
|Patient type||Lower limit||Upper limit||Unit|
|Adult female (follicular
phase, day 5)
95% PI (standard)
90% PI (used
|19 (95% PI)||140 (95% PI)||pg/mL|
|30 (90% PI)||60 (90% PI)|
|Adult female (preovulatory
|Adult female - free
(not protein bound)
|0.5[original research?]||9[original research?]||pg/mL|
|1.7[original research?]||33[original research?]||pmol/L|
|Post-menopausal female||N/A||< 130||pmol/L|
In the normal menstrual cycle, estradiol levels measure typically <50 pg/ml at menstruation, rise with follicular development (peak: 200 pg/ml), drop briefly at ovulation, and rise again during the luteal phase for a second peak. At the end of the luteal phase, estradiol levels drop to their menstrual levels unless there is a pregnancy.
- Hormone replacement therapy (menopause)
- Hormone replacement therapy (male-to-female)
- Estrogen insensitivity syndrome
- Oral contraceptive formulations
- Phytoestrogens, the family of plant chemicals which can act on estradiol receptive tissue in mammals, although the exact mechanism at hand is unclear.
- Bisphenols, a group of human made chemical compounds that mimic estradiol
- Ryan KJ (August 1982). "Biochemistry of aromatase: significance to female reproductive physiology". Cancer Res. 42 (8 Suppl): 3342s–3344s. PMID 7083198.
- Mechoulam R, Brueggemeier RW, Denlinger DL (September 2025). "Estrogens in insects" (PDF). Cellular and Molecular Life Sciences 40 (9): 942–944. doi:10.1007/BF01946450. Check date values in:
- Ozon R (1972). "Estrogens in Fishes, Amphibians, Reptiles, and Birds". In Idler DR. Steroids In Nonmammalian Vertebrates. Oxford: Elsevier Science. pp. 390–414. ISBN 032314098X.
- "Greek Word Study Tool: oistros". Perseus Digital Library. Retrieved 2011-12-28.
- Carreau S, Lambard S, Delalande C, Denis-Galeraud I, Bilinska B, Bourguiba S (2003). "Aromatase expression and role of estrogens in male gonad : a review". Reproductive Biology and Endocrinology 1: 35. doi:10.1186/1477-7827-1-35. PMC 155680. PMID 12747806.
- Pentikäinen V, Erkkilä K, Suomalainen L, Parvinen M, Dunkel L (2000). "Estradiol acts as a germ cell survival factor in the human testis in vitro". The Journal of Clinical Endocrinology and Metabolism 85 (5): 2057–67. doi:10.1210/jc.85.5.2057. PMID 10843196.
- Sharpe RM, Skakkebaek NE (1993). "Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract?". Lancet 341 (8857): 1392–5. doi:10.1016/0140-6736(93)90953-E. PMID 8098802.
- Raman JD, Schlegel PN (2002). "Aromatase inhibitors for male infertility". The Journal of Urology 167 (2 Pt 1): 624–9. doi:10.1016/S0022-5347(01)69099-2. PMID 11792932.
- Visootsak J, Graham JM (2006). "Klinefelter syndrome and other sex chromosomal anueploidies". Orphanet Journal of Rare Diseases 1 (42): 42. doi:10.1186/1750-1172-1-42. PMC 1634840. PMID 17062147. Retrieved 20 November 2013.
- Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER (1997). "Effect of testosterone and estradiol in a man with aromatase deficiency". The New England Journal of Medicine 337 (2): 91–5. doi:10.1056/NEJM199707103370204. PMID 9211678.
- Albright, Fuller; Smith Patricia H.; Richardson Anna M. (31 May 1941). "Postmenopausal Osteoporosis: Its Clinical Features". JAMA 116 (22): 2465–2474. doi:10.1001/jama.1941.02820220007002. Retrieved 20 November 2013.
- Behl C, Widmann M, Trapp T, Holsboer F (November 1995). "17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro". Biochem. Biophys. Res. Commun. 216 (2): 473–82. doi:10.1006/bbrc.1995.2647. PMID 7488136.
- Meethal, S. V.; Liu, T.; Chan, H. W.; Ginsburg, E.; Wilson, A. C.; Gray, D. N.; Bowen, R. L.; Vonderhaar, B. K.; Atwood, C. S. (2009). "Identification of a regulatory loop for the synthesis of neurosteroids: A steroidogenic acute regulatory protein-dependent mechanism involving hypothalamic-pituitary-gonadal axis receptors". Journal of Neurochemistry 110 (3): 1014–1027. doi:10.1111/j.1471-4159.2009.06192.x. PMC 2789665. PMID 19493163.
- Douma SL, Husband C, O'Donnell ME, Barwin BN, Woodend AK (2005). "Estrogen-related mood disorders: reproductive life cycle factors". ANS Adv Nurs Sci 28 (4): 364–75. doi:10.1097/00012272-200510000-00008. PMID 16292022.
- Lasiuk GC, Hegadoren KM (October 2007). "The effects of estradiol on central serotonergic systems and its relationship to mood in women". Biol Res Nurs 9 (2): 147–60. doi:10.1177/1099800407305600. PMID 17909167.
- Hulshoff HE, Cohen-Kettenis PT, Van Haren NE, Peper JS, Brans RG, Cahn W, Schnack HG, Gooren LJ Kahn RS (July 2006). "Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure". European Journal of Endocrinology 155 (155): 107–114. doi:10.1530/eje.1.02248.
- Harding CF (June 2004). "Hormonal Modulation of Singing: Hormonal Modulation of the Songbird Brain and Singing Behavior". Ann. N.Y. Acad. Sci. (The New York Academy of Sciences) 1016: 524–539. doi:10.1196/annals.1298.030. PMID 15313793. Retrieved 2007-03-07.
- Simerly RB (2002-03-27). "Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain" (PDF). Annual Rev. Neurosci. 25: 507–536. doi:10.1146/annurev.neuro.25.112701.142745. PMID 12052919. Retrieved 2007-03-07.
- Collins P, Rosano GM, Sarrel PM, Ulrich L, Adamopoulos S, Beale CM, McNeill JG, Poole-Wilson PA (1995). "17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease". Circulation 92 (1): 24–30. doi:10.1161/01.CIR.92.1.24. PMID 7788912.
- 韋伯顧問醫師 (2011-08-09). 【您應該知道的避孕常識 9】事後緊急避孕 [Common contraception knowledge you shall know (Part 9): Emergency contraception after sex] (in Chinese). Retrieved 2012-07-02.
- Glasier, Anna (2010). "Contraception". In Jameson, J. Larry; De Groot, Leslie J. Endocrinology (6th ed.). Philadelphia: Saunders Elsevier. pp. 2417–2427. ISBN 978-1-4160-5583-9.
- Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 434, 444. ISBN 3-8047-1763-2.
- Ockrim JL, Lalani el-N, Kakkar AK, Abel PD (August 2005). "Transdermal estradiol therapy for prostate cancer reduces thrombophilic activation and protects against thromboembolism". J. Urol. 174 (2): 527–33; discussion 532–3. doi:10.1097/01.ju.0000165567.99142.1f. PMID 16006886.
- Carruba G, Pfeffer U, Fecarotta E, Coviello DA, D'Amato E, Lo Castro M, Vidali G, Castagnetta L (March 1994). "Estradiol inhibits growth of hormone-nonresponsive PC3 human prostate cancer cells". Cancer Res. 54 (5): 1190–3. PMID 8118804.
- Drugs.com: Premarin Official FDA information, side effects and uses.
- Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. pp. 406–. ISBN 978-3-88763-075-1. Retrieved 13 September 2012.
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research On Cancer (2007). Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. World Health Organization. p. 384. ISBN 978-92-832-1291-1. Retrieved 13 September 2012.
- Archana Desai; Mary Lee (7 May 2007). Gibaldi's Drug Delivery Systems in Pharmaceutical Care. ASHP. p. 337. ISBN 978-1-58528-136-7. Retrieved 13 September 2012.
- Rebekah Wang-Cheng; Joan M. Neuner (May 2007). Menopause. ACP Press. p. 96. ISBN 978-1-930513-83-9. Retrieved 13 September 2012.
- Barr Laboratories, Inc. (March 2008). "ESTRACE TABLETS, (estradiol tablets, USP)" (PDF). wcrx.com. Retrieved 27 January 2010.
- Pfizer (August 2008). "ESTRING (estradiol vaginal ring)" (PDF).
- Bulzomi P, Bolli A, Galluzzo P, Leone S, Acconcia F, Marino M (January 2010). "Naringenin and 17β-estradiol coadministration prevents hormone-induced human cancer cell growth". IUBMD Life 62 (1): 51–60. doi:10.1002/iub.279. PMID 19960539.
- Sreeja S, Santhosh Kumar TR, Lakshmi BS, Sreeja S (17 March 2011). "Pomegranate extract demonstrate a selective estrogen receptor modulator profile in human tumor cell lines and in vivo models of estrogen deprivation". Journal of Nutritional Biochemistry 23 (7): 725–32. doi:10.1016/j.jnutbio.2011.03.015. PMID 21839626.
- Thomas CG, Strom A, Lindberg K, Gustafsson JA (22 June 2010). "Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G2/M checkpoint signaling". Breast Cancer Research and Treatment 127 (2): 417–427. doi:10.1007/s10549-010-1011-z. PMID 20623183.
- Walter F. Boron, Emile L. Boulpaep (2003). Medical Physiology: A Cellular And Molecular Approach. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.
- Pardridge WM, Mietus LJ (July 1979). "Transport of Steroid Hormones through the Rat Blood-Brain Barrier". Journal of Clinical Investigation 64 (1): 145–154. doi:10.1172/JCI109433. PMC 372100. PMID 447850.
- Young, I. J.; Hillman, J. R.; Knights, B. A. (1978). "Endogenous Estradiol-17 β in Phaseolus vulgaris". Zeitschrift für Pflanzenphysiologie 90: 45. doi:10.1016/S0044-328X(78)80223-2.
- Prossnitz ER, Barton M (May 2014). "Estrogen biology: New insights into GPER function and clinical opportunities". Mol. Cell. Endocrinol. 389 (1-2): 71–83. doi:10.1016/j.mce.2014.02.002. PMID 24530924.
- Prossnitz ER, Arterburn JB, Sklar LA (February 2007). "GPR30: A G protein-coupled receptor for estrogen". Mol. Cell. Endocrinol. 265-266: 138–42. doi:10.1016/j.mce.2006.12.010. PMC 1847610. PMID 17222505.
- Wu CH, Motohashi T, Abdel-Rahman HA, Flickinger GL, Mikhail G (August 1976). "Free and protein-bound plasma estradiol-17 beta during the menstrual cycle". J. Clin. Endocrinol. Metab. 43 (2): 436–45. doi:10.1210/jcem-43-2-436. PMID 950372.
- Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH (February 2001). "Role of cytochrome P450 in estradiol metabolism in vitro". Acta Pharmacol. Sin. 22 (2): 148–54. PMID 11741520.
- Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT (August 2003). "Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms". Endocrinology 144 (8): 3382–98. doi:10.1210/en.2003-0192. PMID 12865317.
- GPNotebook — reference range (oestradiol) Retrieved on September 27, 2009
- Values taken from day 1 after LH surge in: Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P, Stricker R (2006). "Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer". Clin. Chem. Lab. Med. 44 (7): 883–7. doi:10.1515/CCLM.2006.160. PMID 16776638. as PDF
- Total amount multiplied by 0.022 according to 2.2% presented in: Wu CH, Motohashi T, Abdel-Rahman HA, Flickinger GL, Mikhail G (August 1976). "Free and protein-bound plasma estradiol-17 beta during the menstrual cycle". J. Clin. Endocrinol. Metab. 43 (2): 436–45. doi:10.1210/jcem-43-2-436. PMID 950372.[original research?]