Estrone

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Estrone
Estron.svg
Estrone molecule ball.png
Names
IUPAC name
3-Hydroxyestra-1,3,5(10)-trien-17-one
Systematic IUPAC name
(3aS,3bR,9bS,11aS)-7-Hydroxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthren-1-one
Other names
Oestrone; E1
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.150 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C18H22O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-16,19H,2,4,6-9H2,1H3/t14-,15-,16+,18+/m1/s1 X mark.svgN
    Key: DNXHEGUUPJUMQT-CBZIJGRNSA-N X mark.svgN
  • O=C4[C@]3(CC[C@@H]2c1ccc(O)cc1CC[C@H]2[C@@H]3CC4)C
Properties
C18H22O2
Molar mass 270.366 g/mol
Melting point 254.5
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. [1] It is one of three major endogenous estrogens, the others being estradiol and estriol. [1] Estrone, as well as the other estrogens, are synthesized from cholesterol and secreted mainly from the gonads, though they can also be formed from adrenal androgens in adipose tissue. [2] Relative to estradiol, both estrone and estriol have far weaker activity as estrogens. [1] Estrone can be converted into estradiol, and serves mainly as a precursor or metabolic intermediate of estradiol. [1] [3] It is both a precursor and metabolite of estradiol. [4] [1]

In addition to its role as a natural hormone, estrone has been used as a medication, for instance in menopausal hormone therapy; for information on estrone as a medication, see the estrone (medication) article.

Biological activity

Estrone is an estrogen, specifically an agonist of the estrogen receptors ERα and ERβ. [1] [5] It is a far less potent estrogen than is estradiol, and as such, is a relatively weak estrogen. [1] [5] [6] Given by subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol. [7] According to one study, the relative binding affinities of estrone for the human ERα and ERβ were 4.0% and 3.5% of those estradiol, respectively, and the relative transactivational capacities of estrone at the ERα and ERβ were 2.6% and 4.3% of those of estradiol, respectively. [5] In accordance, the estrogenic activity of estrone has been reported to be approximately 4% of that of estradiol. [1] In addition to its low estrogenic potency, estrone, unlike estradiol and estriol, is not accumulated in estrogen target tissues. [1] Because estrone can be transformed into estradiol, most or all of the estrogenic potency of estrone in vivo is actually due to conversion into estradiol. [1] [8] As such, estrone is considered to be a precursor or prohormone of estradiol. [3] In contrast to estradiol and estriol, estrone is not a ligand of the G protein-coupled estrogen receptor (affinity >10,000 nM). [9]

Clinical research has confirmed the nature of estrone as a relatively inert precursor of estradiol. [1] [10] [11] [12] With oral administration of estradiol, the ratio of estradiol levels to estrone levels is about 5 times higher on average than under normal physiological circumstances in premenopausal women and with parenteral (non-oral) routes of estradiol. [1] Oral administration of menopausal replacement dosages of estradiol results in low, follicular phase levels of estradiol, whereas estrone levels resemble the high levels seen during the first trimester of pregnancy. [1] [13] [14] In spite of markedly elevated levels of estrone with oral estradiol but not with transdermal estradiol, clinical studies have shown that dosages of oral and transdermal estradiol achieving similar levels of estradiol possess equivalent and non-significantly different potency in terms of measures including suppression of luteinizing hormone and follicle-stimulating hormone levels, inhibition of bone resorption, and relief of menopausal symptoms such as hot flashes. [1] [10] [11] [12] [15] In addition, estradiol levels were found to correlate with these effects, while estrone levels did not. [10] [11] These findings confirm that estrone has very low estrogenic activity, and also indicate that estrone does not diminish the estrogenic activity of estradiol. [1] [10] [11] [12] This contradicts some cell-free in-vitro research suggesting that high concentrations of estrone might be able to partially antagonize the actions of estradiol. [16] [17] [18]

Selected biological properties of endogenous estrogens in rats
Estrogen ER Tooltip Estrogen receptor RBA Tooltip relative binding affinity (%) Uterine weight (%) Uterotrophy LH Tooltip Luteinizing hormone levels (%) SHBG Tooltip Sex hormone-binding globulin RBA Tooltip relative binding affinity (%)
Control–100–100–
Estradiol (E2) 100506 ± 20+++12–19100
Estrone (E1) 11 ± 8490 ± 22+++ ?20
Estriol (E3) 10 ± 4468 ± 30+++8–183
Estetrol (E4) 0.5 ± 0.2 ?Inactive ?1
17α-Estradiol 4.2 ± 0.8 ? ? ? ?
2-Hydroxyestradiol 24 ± 7285 ± 8+b31–6128
2-Methoxyestradiol 0.05 ± 0.04101Inactive ?130
4-Hydroxyestradiol 45 ± 12 ? ? ? ?
4-Methoxyestradiol 1.3 ± 0.2260++ ?9
4-Fluoroestradiol a180 ± 43 ?+++ ? ?
2-Hydroxyestrone 1.9 ± 0.8130 ± 9Inactive110–1428
2-Methoxyestrone 0.01 ± 0.00103 ± 7Inactive95–100120
4-Hydroxyestrone 11 ± 4351++21–5035
4-Methoxyestrone 0.13 ± 0.04338++65–9212
16α-Hydroxyestrone 2.8 ± 1.0552 ± 42+++7–24<0.5
2-Hydroxyestriol 0.9 ± 0.3302+b ? ?
2-Methoxyestriol 0.01 ± 0.00 ?Inactive ?4
Notes: Values are mean ± SD or range. ERRBA = Relative binding affinity to estrogen receptors of rat uterine cytosol. Uterine weight = Percentage change in uterine wet weight of ovariectomized rats after 72 hours with continuous administration of 1 μg/hour via subcutaneously implanted osmotic pumps. LH levels = Luteinizing hormone levels relative to baseline of ovariectomized rats after 24 to 72 hours of continuous administration via subcutaneous implant. Footnotes:a = Synthetic (i.e., not endogenous). b = Atypical uterotrophic effect which plateaus within 48 hours (estradiol's uterotrophy continues linearly up to 72 hours). Sources: See template.

Biochemistry

Comprehensive overview of steroidogenesis, showing estrone on the lower right among the estrogens. Steroidogenesis.svg
Comprehensive overview of steroidogenesis, showing estrone on the lower right among the estrogens.

Biosynthesis

Estrone is biosynthesized from cholesterol. The principal pathway involves androstenedione as an intermediate, with androstenedione being transformed into estrone by the enzyme aromatase. This reaction occurs in both the gonads and in certain other tissues, particularly adipose tissue, and estrone is subsequently secreted from these tissues. [2] In addition to aromatization of androstenedione, estrone is also formed reversibly from estradiol by the enzyme 17β-hydroxysteroid dehydrogenase (17β-HSD) in various tissues, including the liver, uterus, and mammary gland. [1]

Mechanism of Action:

The way estrone works is by entering the cells of certain tissues in the body and attaching to nuclear receptors. This interaction then influences how genes are expressed, leading to various physiological responses in the body. [20]

Distribution

Estrone is bound approximately 16% to sex hormone-binding globulin (SHBG) and 80% to albumin in the circulation, [1] with the remainder (2.0 to 4.0%) circulating freely or unbound. [21] It has about 24% of the relative binding affinity of estradiol for SHBG. [1] As such, estrone is relatively poorly bound to SHBG. [22]

Metabolism

Estrone is conjugated into estrogen conjugates such as estrone sulfate and estrone glucuronide by sulfotransferases and glucuronidases, and can also be hydroxylated by cytochrome P450 enzymes into catechol estrogens such as 2-hydroxyestrone and 4-hydroxyestrone or into estriol. [1] Both of these transformations take place predominantly in the liver. [1] Estrone can also be reversibly converted into estradiol by 17β-HSD. [1] The blood half-life of estrone is about 10 to 70 minutes and is similar to that of estradiol. [23] [24]

Interactive icon.svg
Description: The metabolic pathways involved in the metabolism of estradiol and other natural estrogens (e.g., estrone, estriol) in humans. In addition to the metabolic transformations shown in the diagram, conjugation (e.g., sulfation and glucuronidation) occurs in the case of estradiol and metabolites of estradiol that have one or more available hydroxyl (–OH) groups. Sources: See template page.

Excretion

Estrone is excreted in urine in the form of estrogen conjugates such as estrone sulfate. [1] Following an intravenous injection of labeled estrone in women, almost 90% is excreted in urine and feces within 4 to 5 days. [23] Enterohepatic recirculation causes a delay in excretion of estrone. [23]

It is one of the three primary types of estrogen and is produced in various parts of the body, including the placenta, ovaries, and peripheral tissues. [25]

Levels

Production rates, secretion rates, clearance rates, and blood levels of major sex hormones
SexSex hormoneReproductive
phase		Blood
production rate		Gonadal
secretion rate		Metabolic
clearance rate		Reference range (serum levels)
SI unitsNon-SI units
Men Androstenedione
–
2.8 mg/day1.6 mg/day2200 L/day2.8–7.3 nmol/L80–210 ng/dL
Testosterone
–
6.5 mg/day6.2 mg/day950 L/day6.9–34.7 nmol/L200–1000 ng/dL
Estrone
–
150 μg/day110 μg/day2050 L/day37–250 pmol/L10–70 pg/mL
Estradiol
–
60 μg/day50 μg/day1600 L/day<37–210 pmol/L10–57 pg/mL
Estrone sulfate
–
80 μg/dayInsignificant167 L/day600–2500 pmol/L200–900 pg/mL
Women Androstenedione
–
3.2 mg/day2.8 mg/day2000 L/day3.1–12.2 nmol/L89–350 ng/dL
Testosterone
–
190 μg/day60 μg/day500 L/day0.7–2.8 nmol/L20–81 ng/dL
EstroneFollicular phase110 μg/day80 μg/day2200 L/day110–400 pmol/L30–110 pg/mL
Luteal phase260 μg/day150 μg/day2200 L/day310–660 pmol/L80–180 pg/mL
Postmenopause40 μg/dayInsignificant1610 L/day22–230 pmol/L6–60 pg/mL
Estradiol Follicular phase90 μg/day80 μg/day1200 L/day<37–360 pmol/L10–98 pg/mL
Luteal phase250 μg/day240 μg/day1200 L/day699–1250 pmol/L190–341 pg/mL
Postmenopause6 μg/dayInsignificant910 L/day<37–140 pmol/L10–38 pg/mL
Estrone sulfate Follicular phase100 μg/dayInsignificant146 L/day700–3600 pmol/L250–1300 pg/mL
Luteal phase180 μg/dayInsignificant146 L/day1100–7300 pmol/L400–2600 pg/mL
Progesterone Follicular phase2 mg/day1.7 mg/day2100 L/day0.3–3 nmol/L0.1–0.9 ng/mL
Luteal phase25 mg/day24 mg/day2100 L/day19–45 nmol/L6–14 ng/mL
Notes and sources
Notes: "The concentration of a steroid in the circulation is determined by the rate at which it is secreted from glands, the rate of metabolism of precursor or prehormones into the steroid, and the rate at which it is extracted by tissues and metabolized. The secretion rate of a steroid refers to the total secretion of the compound from a gland per unit time. Secretion rates have been assessed by sampling the venous effluent from a gland over time and subtracting out the arterial and peripheral venous hormone concentration. The metabolic clearance rate of a steroid is defined as the volume of blood that has been completely cleared of the hormone per unit time. The production rate of a steroid hormone refers to entry into the blood of the compound from all possible sources, including secretion from glands and conversion of prohormones into the steroid of interest. At steady state, the amount of hormone entering the blood from all sources will be equal to the rate at which it is being cleared (metabolic clearance rate) multiplied by blood concentration (production rate = metabolic clearance rate × concentration). If there is little contribution of prohormone metabolism to the circulating pool of steroid, then the production rate will approximate the secretion rate." Sources: See template.

Toxicity:

When estrone is used too much or taken in large amounts, it can cause toxicity, leading to symptoms like nausea and vomiting. Estrone should be stored in its original package or container to maintain its quality and effectiveness. [25]

Chemistry

Structures of major endogenous estrogens
Chemical structures of major endogenous estrogens no labels.png
Estrone (E1)
Estradiol (E2)
Estriol (E3)
Estetrol (E4)
Interactive icon.svg
Note the hydroxyl (–OH) groups: estrone (E1) has one, estradiol (E2) has two, estriol (E3) has three, and estetrol (E4) has four.

Estrone, also known as estra-1,3,5(10)-trien-3-ol-17-one, is a naturally occurring estrane steroid with double bonds at the C1, C3, and C5 positions, a hydroxyl group at the C3 position, and a ketone group at the C17 position. The name estrone was derived from the chemical terms estrin (estra-1,3,5(10)-triene) and ketone.

The chemical formula of estrone is C18H22O2 and its molecular weight is 270.366 g/mol. It is a white, odorless, solid crystalline powder, with a melting point of 254.5 °C (490 °F) and a specific gravity of 1.23. [26] [27] Estrone is combustible at high temperatures, with the products carbon monoxide (CO) and carbon dioxide (CO2). [26]

Medical use

Estrone has been available as an injected estrogen for medical use, for instance in hormone therapy for menopausal symptoms, but it is now mostly no longer marketed. [28]

Estrone, as part of hormone replacement therapy (HRT), is frequently used to treat symptoms caused by estrogen deficiency in peri and post-menopausal women. This therapy aims to enhance overall health and relieve menopausal symptoms related to estrogen imbalance. Additionally, estrone and other estrogens are used to prevent osteoporosis in postmenopausal women who are at high risk of fractures and cannot tolerate alternative medications. Estrogens are absorbed efficiently by the body and subsequently inactivated in the liver, making them effective in HRT and osteoporosis prevention. [25]

Contraindications

The use of estrone has several contraindications, some examples including: hypersensitivity, history of some cancers, stroke, venous thromboembolism (VTE), and those currently pregnant or breastfeeding. Estrogens hold a boxed warning to be used at the lowest effective dose and for the shortest possible treatment period if used alone or with another hormone in the progestogen class. [29]

Breast Cancer

Estrone is contraindicated for those that have or are suspected of having breast cancer. The use of estrogens hold a boxed warning with breast cancer for post-menopausal women as this can increase the risk of developing invasive breast cancer. [30] Those with breast cancer become at a greater risk of hypercalcemia and bone metastases when taking estrogens. [31] Post-menopausal women with breast cancer can be seen to develop frailty syndrome when there are changes in blood hormonal levels, including an increased level of estrone. Estrone, the major type of estrogen produced in post-menopausal women, was seen in greater concentrations from standard levels in those that were categorized as prefrail and in those that classified as frail. [32]

Venous Thromboembolism

The risk of VTE is increased in those that use estrogens, those that currently have or have a history with VTE are at a greater risk of reoccurring VTE with the usage of estrogens. [30] [33] The use of estrogens within three weeks postpartum may increase the risk of developing a VTE. [34] Risk of developing initial VTE is also increased with familial history, genetic mutations: factor V Leiden and prothrombin-G20210A, and pregnancy-postpartum with the use of estrogens. [35]

Breastfeeding

The use of estrogens may affect the ability to breastfeed and can change the composition of breastmilk. Estrogens have been used to suppress lactation which can result in a reduced total duration of lactation and reduced volume or inability to produce breastmilk. Composition of breastmilk produced was also seen to be different resulting in a reduced concentration of proteins in the milk. Babies of mothers that were taking estrogens while breastfeeding were seen to experience slower weight gain. [34]

Side effects

Common

Some common side effects seen with the usage of estrogens include: breast swelling, breast tenderness, vaginal itching, abnormal uterine bleeding, weight gain, hair loss, jaundice, and anaphylaxis. [36]

Adverse effect

Some adverse effects seen with the usage of estrogens include: increased risk of venous thromboembolism (VTE), stroke, breast cancer, hypertension, and vaginitis. [36] [29]

History

Estrone was the first steroid hormone to be discovered. [37] [38] It was discovered in 1929 independently by the American scientists Edward Doisy and Edgar Allen and the German biochemist Adolf Butenandt, although Doisy and Allen isolated it two months before Butenandt. [37] [39] [40] They isolated and purified estrone in crystalline form from the urine of pregnant women. [39] [40] [41] Doisy and Allen named it theelin, while Butenandt named it progynon and subsequently referred to it as folliculin in his second publication on the substance. [40] [42] Butenandt was later awarded the Nobel Prize in 1939 for the isolation of estrone and his work on sex hormones in general. [41] [43] The molecular formula of estrone was known by 1931, [44] and its chemical structure had been determined by Butenandt by 1932. [40] [39] Following the elucidation of its structure, estrone was additionally referred to as ketohydroxyestrin or oxohydroxyestrin, [45] [46] and the name estrone, on the basis of its C17 ketone group, was formally established in 1932 at the first meeting of the International Conference on the Standardization of Sex Hormones in London. [47] [48]

A partial synthesis of estrone from ergosterol was accomplished by Russell Earl Marker in 1936, and was the first chemical synthesis of estrone. [49] [50] An alternative partial synthesis of estrone from cholesterol by way of dehydroepiandrosterone (DHEA) was developed by Hans Herloff Inhoffen and Walter Hohlweg in 1939 or 1940, [49] and a total synthesis of estrone was achieved by Anner and Miescher in 1948. [48]

Approval

The FDA has approved estrone based on its safety and effectiveness as per the rules outlined in sections 505 of the Federal Food, Drug, and Cosmetic Act. [25]

Related Research Articles

<span class="mw-page-title-main">Estrogen</span> Primary female sex hormone

Estrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy.

<span class="mw-page-title-main">Estradiol</span> Chemical compound

Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips and a female pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus and vagina during puberty, adulthood and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain.

<span class="mw-page-title-main">Progestogen (medication)</span> Medication producing effects similar to progesterone

A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy. They can also be used in the treatment of gynecological conditions, to support fertility and pregnancy, to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone.

<span class="mw-page-title-main">Estriol</span> Chemical compound

Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estrone. Levels of estriol in women who are not pregnant are almost undetectable. However, during pregnancy, estriol is synthesized in very high quantities by the placenta and is the most produced estrogen in the body by far, although circulating levels of estriol are similar to those of other estrogens due to a relatively high rate of metabolism and excretion. Relative to estradiol, both estriol and estrone have far weaker activity as estrogens.

<span class="mw-page-title-main">Ethinylestradiol</span> Estrogen medication

Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.

<span class="mw-page-title-main">Estrone sulfate</span> Chemical compound

Estrone sulfate, also known as E1S, E1SO4 and estrone 3-sulfate, is a natural, endogenous steroid and an estrogen ester and conjugate.

<span class="mw-page-title-main">Estetrol</span> Chemical compound

Estetrol (E4), or oestetrol, is one of the four natural estrogenic steroid hormones found in humans, along with estrone (E1), estradiol (E2), and estriol (E3). Estetrol is a major estrogen in the body. In contrast to estrone and estradiol, estetrol is a native estrogen of fetal life. Estetrol is produced exclusively by the fetal liver and is found in detectable levels only during pregnancy, with relatively high levels in the fetus and lower levels in the maternal circulation.

<span class="mw-page-title-main">Nomegestrol acetate</span> Chemical compound

Nomegestrol acetate (NOMAC), sold under the brand names Lutenyl and Zoely among others, is a progestin medication which is used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. It is available both alone and in combination with an estrogen. NOMAC is taken by mouth. A birth control implant for placement under the skin was also developed but ultimately was not marketed.

<span class="mw-page-title-main">Esterified estrogens</span> Pharmaceutical drug

Esterified estrogens (EEs), sold under the brand names Estratab and Menest among others, is an estrogen medication which is used hormone therapy for menopausal symptoms and low sex hormone levels in women, to treat breast cancer in both women and men, and to treat prostate cancer in men. It is formulated alone or in combination with methyltestosterone. It is taken by mouth.

<span class="mw-page-title-main">Conjugated estrogens</span> Estrogen medication

Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen medication which is used in menopausal hormone therapy and for various other indications. It is a mixture of the sodium salts of estrogen conjugates found in horses, such as estrone sulfate and equilin sulfate. CEEs are available in the form of both natural preparations manufactured from the urine of pregnant mares and fully synthetic replications of the natural preparations. They are formulated both alone and in combination with progestins such as medroxyprogesterone acetate. CEEs are usually taken by mouth, but can also be given by application to the skin or vagina as a cream or by injection into a blood vessel or muscle.

<span class="mw-page-title-main">Estradiol sulfate</span> Chemical compound

Estradiol sulfate (E2S), or 17β-estradiol 3-sulfate, is a natural, endogenous steroid and an estrogen ester. E2S itself is biologically inactive, but it can be converted by steroid sulfatase into estradiol, which is a potent estrogen. Simultaneously, estrogen sulfotransferases convert estradiol to E2S, resulting in an equilibrium between the two steroids in various tissues. Estrone and E2S are the two immediate metabolic sources of estradiol. E2S can also be metabolized into estrone sulfate (E1S), which in turn can be converted into estrone and estradiol. Circulating concentrations of E2S are much lower than those of E1S. High concentrations of E2S are present in breast tissue, and E2S has been implicated in the biology of breast cancer via serving as an active reservoir of estradiol.

<span class="mw-page-title-main">Estradiol (medication)</span> Steroidal hormone medication

Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in feminizing hormone therapy for transgender women and some non-binary individuals, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.

<span class="mw-page-title-main">Estrogen (medication)</span> Type of medication

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

<span class="mw-page-title-main">Estriol (medication)</span> Chemical compound

Estriol (E3), sold under the brand name Ovestin among others, is an estrogen medication and naturally occurring steroid hormone which is used in menopausal hormone therapy. It is also used in veterinary medicine as Incurin to treat urinary incontinence due to estrogen deficiency in dogs. The medication is taken by mouth in the form of tablets, as a cream that is applied to the skin, as a cream or pessary that is applied in the vagina, and by injection into muscle.

<span class="mw-page-title-main">Estrone (medication)</span> Estrogen medication

Estrone (E1), sold under the brand names Estragyn, Kestrin, and Theelin among many others, is an estrogen medication and naturally occurring steroid hormone which has been used in menopausal hormone therapy and for other indications. It has been provided as an aqueous suspension or oil solution given by injection into muscle and as a vaginal cream applied inside of the vagina. It can also be taken by mouth as estradiol/estrone/estriol and in the form of prodrugs like estropipate and conjugated estrogens.

<span class="mw-page-title-main">Estetrol (medication)</span> Estrogen medication

Estetrol (E4) is an estrogen medication and naturally occurring steroid hormone which is used in combination with a progestin in combined birth control pills and is under development for various other indications. These investigational uses include menopausal hormone therapy to treat symptoms such as vaginal atrophy, hot flashes, and bone loss and the treatment of breast cancer and prostate cancer. It is taken by mouth.

<span class="mw-page-title-main">Estrone sulfate (medication)</span> Chemical compound

Estrone sulfate (E1S) is an estrogen medication and naturally occurring steroid hormone. It is used in menopausal hormone therapy among other indications. As the sodium salt, it is the major estrogen component of conjugated estrogens (Premarin) and esterified estrogens. In addition, E1S is used on its own as the piperazine salt estropipate. The compound also occurs as a major and important metabolite of estradiol and estrone. E1S is most commonly taken by mouth, but in the form of Premarin can also be taken by parenteral routes such as transdermal, vaginal, and injection.

<span class="mw-page-title-main">Pharmacokinetics of estradiol</span>

The pharmacology of estradiol, an estrogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.

<span class="mw-page-title-main">Conjugated estriol</span> Pharmaceutical drug

Conjugated estriol, sold under the brand names Progynon and Emmenin, is an estrogen medication which was previously used for estrogen-type indications such as the treatment of menopausal symptoms in women. The term specifically refers to formulations of estriol conjugates which were manufactured from the estrogen-rich urine of pregnant women and were used as medications in the 1920s and 1930s. Conjugated estriol is analogous to and was superseded by conjugated estrogens, which is manufactured from the urine of pregnant mares. Conjugated estriol was among the first forms of pharmaceutical estrogen to be used in medicine. It was taken by mouth.

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  6. ↑ Ruggiero RJ, Likis FE (2002). "Estrogen: physiology, pharmacology, and formulations for replacement therapy". Journal of Midwifery & Women's Health. 47 (3): 130–138. doi:10.1016/s1526-9523(02)00233-7. PMID   12071379.
  7. ↑ Labhart A (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 548–. ISBN   978-3-642-96158-8.
  8. ↑ Fishman J, Martucci CP (1980). "New Concepts of Estrogenic Activity: The Role of Metabolites in the Expression of Hormone Action". In Pasetto N, Paoletti R, Ambrus JL (eds.). The Menopause and Postmenopause. Springer. pp. 43–52. doi:10.1007/978-94-011-7230-1_5. ISBN   978-94-011-7232-5.
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  12. 1 2 3 Fåhraeus L, Larsson-Cohn U (December 1982). "Oestrogens, gonadotrophins and SHBG during oral and cutaneous administration of oestradiol-17 beta to menopausal women". Acta Endocrinologica. 101 (4): 592–596. doi:10.1530/acta.0.1010592. PMID   6818806.
  13. ↑ Wright JV (December 2005). "Bio-identical steroid hormone replacement: selected observations from 23 years of clinical and laboratory practice". Annals of the New York Academy of Sciences. 1057 (1): 506–524. Bibcode:2005NYASA1057..506W. doi:10.1196/annals.1356.039. PMID   16399916. S2CID   38877163.
  14. ↑ Friel PN, Hinchcliffe C, Wright JV (March 2005). "Hormone replacement with estradiol: conventional oral doses result in excessive exposure to estrone". Alternative Medicine Review. 10 (1): 36–41. PMID   15771561.
  15. ↑ De Lignieres B, Basdevant A, Thomas G, Thalabard JC, Mercier-Bodard C, Conard J, et al. (March 1986). "Biological effects of estradiol-17 beta in postmenopausal women: oral versus percutaneous administration". The Journal of Clinical Endocrinology and Metabolism. 62 (3): 536–541. doi:10.1210/jcem-62-3-536. PMID   3080464.
  16. ↑ Kloosterboer HJ, Schoonen WG, Verheul HA (11 April 2008). "Proliferation of Breast Cells by Steroid Hormones and Their Metabolites". In Pasqualini JR (ed.). Breast Cancer: Prognosis, Treatment, and Prevention. CRC Press. pp. 343–366. ISBN   978-1-4200-5873-4.
  17. ↑ Sasson S, Notides AC (July 1983). "Estriol and estrone interaction with the estrogen receptor. II. Estriol and estrone-induced inhibition of the cooperative binding of [3H]estradiol to the estrogen receptor". The Journal of Biological Chemistry. 258 (13): 8118–8122. doi: 10.1016/S0021-9258(20)82036-5 . PMID   6863280.
  18. ↑ Lundström E, Conner P, Naessén S, Löfgren L, Carlström K, Söderqvist G (2015). "Estrone - a partial estradiol antagonist in the normal breast". Gynecological Endocrinology. 31 (9): 747–749. doi:10.3109/09513590.2015.1062866. PMID   26190536. S2CID   13617050.
  19. ↑ Häggström M, Richfield D (2014). "Diagram of the pathways of human steroidogenesis". WikiJournal of Medicine. 1 (1). doi: 10.15347/wjm/2014.005 . ISSN   2002-4436.
  20. ↑ Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID   16112947. S2CID   24616324.
  21. ↑ Jameson JL, De Groot LJ (18 May 2010). Endocrinology – E-Book: Adult and Pediatric. Elsevier Health Sciences. pp. 2813–. ISBN   978-1-4557-1126-0.
  22. ↑ Buchsbaum HJ (6 December 2012). The Menopause. Springer Science & Business Media. pp. 62, 64. ISBN   978-1-4612-5525-3.
  23. 1 2 3 Dorfman RI (1961). "Steroid Hormone Metabolism". Radioactive Isotopes in Physiology Diagnostics and Therapy / Künstliche Radioaktive Isotope in Physiologie Diagnostik und Therapie. Springer. pp. 1223–1241. doi:10.1007/978-3-642-49761-2_39. ISBN   978-3-642-49477-2.
  24. ↑ Sandberg AA, Slaunwhite WR (August 1957). "Studies on phenolic steroids in human subjects. II. The metabolic fate and hepato-biliary-enteric circulation of C14-estrone and C14-estradiol in women". The Journal of Clinical Investigation. 36 (8): 1266–1278. doi:10.1172/JCI103524. PMC   1072719 . PMID   13463090.
  25. 1 2 3 4 "Estrogen". PubChem. U.S. National Library of Medicine.
  26. 1 2 "Material Safety Data Sheet Estrone" (PDF). ScienceLab.com. Retrieved 21 February 2013.
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  28. ↑ "Drugs@FDA: FDA Approved Drug Products".
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  30. 1 2 Crandall CJ, Hovey KM, Andrews CA, Chlebowski RT, Stefanick ML, Lane DS, et al. (January 2018). "Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study". Menopause. 25 (1): 11–20. doi:10.1097/GME.0000000000000956. PMC   5734988 . PMID   28816933.
  31. ↑ The NAMS 2017 Hormone Therapy Position Statement Advisory Panel (July 2017). "The 2017 hormone therapy position statement of The North American Menopause Society". Menopause. 24 (7): 728–753. doi:10.1097/GME.0000000000000921. PMID   28650869.{{cite journal}}: |author1= has generic name (help)CS1 maint: numeric names: authors list (link)
  32. ↑ García-Sánchez J, Mafla-España MA, Tejedor-Cabrera C, Avellán-Castillo O, Torregrosa MD, Cauli O (March 2022). "Plasma Aromatase Activity Index, Gonadotropins and Estrone Are Associated with Frailty Syndrome in Post-Menopausal Women with Breast Cancer". Current Oncology. 29 (3): 1744–1760. doi: 10.3390/curroncol29030144 . PMC   8947022 . PMID   35323344.
  33. ↑ "Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis". academic.oup.com. Retrieved 31 July 2023.
  34. 1 2 "Contraceptives, Oral, Combined", Drugs and Lactation Database (LactMed®), Bethesda (MD): National Institute of Child Health and Human Development, 2006, PMID   30000354 , retrieved 31 July 2023
  35. ↑ van Vlijmen EF, Veeger NJ, Middeldorp S, Hamulyák K, Prins MH, Büller HR, Meijer K (August 2011). "Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception". Blood. 118 (8): 2055–61, quiz 2375. doi: 10.1182/blood-2011-03-345678 . PMID   21659542.
  36. 1 2 Delgado BJ, Lopez-Ojeda W (2023). "Estrogen". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   30855848 . Retrieved 31 July 2023.
  37. 1 2 Bullough VL (19 May 1995). Science In The Bedroom: A History Of Sex Research. Basic Books. pp. 128–. ISBN   978-0-465-07259-0. When Allen and Doisy heard about the [Ascheim-Zondek test for the diagnosis of pregnancy], they realized there was a rich and easily handled source of hormones in urine from which they could develop a potent extract. [...] Allen and Doisy's research was sponsored by the committee, while that of their main rival, Adolt Butenandt (b. 1903) of the University of Gottingen was sponsored by a German pharmaceutical firm. In 1929, both terms announced the isolation of a pure crystal female sex hormone, estrone, in 1929, although Doisy and Allen did so two months earlier than Butenandt.27 By 1931, estrone was being commercially produced by Parke Davis in this country, and Schering-Kahlbaum in Germany. Interestingly, when Butenandt (who shared the Nobel Prize for chemistry in 1939) isolated estrone and analyzed its structure, he found that it was a steroid, the first hormone to be classed in this molecular family.[ permanent dead link ]
  38. ↑ Nielsch U, Fuhrmann U, Jaroch S (30 March 2016). New Approaches to Drug Discovery. Springer. pp. 7–. ISBN   978-3-319-28914-4. The first steroid hormone was isolated from the urine of pregnant women by Adolf Butenandt in 1929 (estrone; see Fig. 1) (Butenandt 1931).
  39. 1 2 3 Parl FF (2000). Estrogens, Estrogen Receptor and Breast Cancer. IOS Press. pp. 4–5. ISBN   978-0-9673355-4-4. [Doisy] focused his research on the isolation of female sex hormones from hundreds of gallons of human pregnancy urine based on the discovery by Ascheim and Zondeck in 1927 that the urine of pregnant women possessed estrogenic activity [9]. In the summer of 1929, Doisy succeeded in the isolated of estrone (named by him theelin), simultaneously with but independent of Adolf Butenandt of the University of Gottingen in Germany. Doisy presented his results on the crystallization of estrone at the XIII International Physiological Congress in Boston in August 1929 [10].
  40. 1 2 3 4 Laylin JK (30 October 1993). Nobel Laureates in Chemistry, 1901–1992. Chemical Heritage Foundation. pp. 255–. ISBN   978-0-8412-2690-6. Adolt Friedrich Johann Butenandt was awarded the Nobel Prize in chemistry in 1939 "for his work on sex hormones"; [...] In 1929 Butenandt isolated estrone [...] in pure crystalline form. [...] Both Butenandt and Edward Doisy isolated estrone simultaneously but independently in 1929. [...] Butenandt took a big step forward in the history of biochemistry when he isolated estrone from the urine of pregnant women. [...] He named it "progynon" in his first publication, and then "folliculine", [...] By 1932, [...] he could determine its chemical structure, [...]
  41. 1 2 Greenberg A (14 May 2014). Chemistry: Decade by Decade. Infobase Publishing. pp. 127–. ISBN   978-1-4381-0978-7. Rational chemical studies of human sex hormones began in 1929 with Adolph Butenandt's isolation of pure crystalline estrone, the follicular hormone, from the urine of pregnant women. [...] Butenandt and Ruzicka shared the 1939 Nobel Prize in chemistry.
  42. ↑ Labhart A (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 511–. ISBN   978-3-642-96158-8. E. A. Doisy and A. Butenandt reported almost at the same time on the isolation of an estrogen-active substance in crystalline form from the urine of pregnant women. N. K. Adam suggested that this substance be named estrone because of the C-17-ketone group present (1933).
  43. ↑ Rooke T (1 January 2012). The Quest for Cortisone. MSU Press. pp. 54–. ISBN   978-1-60917-326-5. In 1929 the first estrogen, a steroid called "estrone," was isolated and purified by Doisy; he later won a Nobel Prize for this work.
  44. ↑ Loriaux DL (23 February 2016). "Russel Earl Marker (1902–1995) - The Mexican Yam". A Biographical History of Endocrinology. Wiley. pp. 345–. ISBN   978-1-119-20247-9.
  45. ↑ Campbell AD (1933). "Concerning Placental Hormones and Menstrual Disorders". Annals of Internal Medicine. 7 (3): 330. doi:10.7326/0003-4819-7-3-330. ISSN   0003-4819.
  46. ↑ Fluhmann CF (November 1938). "Estrogenic Hormones: Their Clinical Usage". California and Western Medicine. 49 (5): 362–366. PMC   1659459 . PMID   18744783.
  47. ↑ Fritz MA, Speroff L (28 March 2012). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 750–. ISBN   978-1-4511-4847-3. In 1926, Sir Alan S. Parkes and C.W Bellerby coined the basic word "estrin" to designate the hormone or hormones that induce estrus in animals, the time when female mammals are fertile and receptive to males. [...] The terminology was extended to include the principal estrogens in humans, estrone, estradiol, and estriol, in 1932 at the first meeting of the International Conference on the Standardization of Sex Hormones in London, [...]
  48. 1 2 Oettel M, Schillinger E (6 December 2012). Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens. Springer Science & Business Media. pp. 2–. ISBN   978-3-642-58616-3. The structure of the estrogenic hormones was stated by Butenandt, Thayer, Marrian, and Hazlewood in 1930 and 1931 (see Butenandt 1980). Following the proposition of the Marrian group, the estrogenic hormones were given the trivial names of estradiol, estrone, and estriol. At the first meeting of the International Conference on the Standardization of Sex Hormones, in London (1932), a standard preparation of estrone was established. [...] The partial synthesis of estradiol and estrone from cholesterol and dehydroepiandrosterone was accomplished by Inhoffen and Howleg (Berlin 1940); the total synthesis was achieved by Anner and Miescher (Basel, 1948).
  49. 1 2 Watkins ES (6 March 2007). "Beginnings". The Estrogen Elixir: A History of Hormone Replacement Therapy in America. JHU Press. pp. 21–. ISBN   978-0-8018-8602-7.
  50. ↑ Pincus G, Thimann KV (2 December 2012). The Hormones V1: Physiology, Chemistry and Applications. Elsevier. pp. 360–. ISBN   978-0-323-14206-9.
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