Estradiol

Source: Wikipedia, the free encyclopedia.

Estradiol
The chemical structure of estradiol.
A ball-and-stick model of estradiol.
Names
Pronunciation /ˌɛstrəˈdl/ ES-trə-DY-ohl[1][2]
IUPAC name
Estra-1,3,5(10)-triene-3,17β-diol
Systematic IUPAC name
(1S,3aS,3bR,9bS,11aS)-11a-Methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1H-cyclopenta[a]phenanthrene-1,7-diol
Other names
Oestradiol; E2; 17β-Estradiol; 17β-Oestradiol
Identifiers
3D model (
JSmol
)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard
100.000.022 Edit this at Wikidata
EC Number
  • 200-023-8
KEGG
UNII
  • InChI=1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17+,18+/m1/s1 checkY
    Key: VOXZDWNPVJITMN-ZBRFXRBCSA-N checkY
  • C[C@]12CC[C@@H]3c4ccc(cc4CC[C@H]3[C@@H]1CC[C@@H]2O)O
Properties
C18H24O2
Molar mass 272.38 g/mol
-186.6·10−6 cm3/mol
Pharmacology
G03CA03 (WHO)
License data
Pharmacokinetics:
Oral: <5%[3]
~98%:[3][4]
Albumin: 60%
SHBG: 38%
• Free: 2%
Liver (via hydroxylation, sulfation, glucuronidation)
Oral: 13–20 hours[3]
Sublingual: 8–18 hours[5]
Topical (gel): 36.5 hours[6]
Urine: 54%[3]
Feces: 6%[3]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Estradiol (E2), also spelled oestradiol, is an

adulthood and pregnancy.[7] It also has important effects in many other tissues including bone, fat, skin, liver, and the brain
.

Though estradiol levels in males are much lower than in females, estradiol has important roles in males as well. Apart from humans and other mammals, estradiol is also found in most vertebrates and crustaceans, insects, fish, and other animal species.[8][9]

Estradiol is produced especially within the

intermediates.[10] The major pathway involves the formation of androstenedione, which is then converted by aromatase into estrone and is subsequently converted into estradiol. Alternatively, androstenedione can be converted into testosterone, which can then be converted into estradiol. Upon menopause
in females, production of estrogens by the ovaries stops and estradiol levels decrease to very low levels.

In addition to its role as a natural hormone, estradiol is used as a

menopausal hormone therapy and feminizing hormone therapy for transgender women; for information on estradiol as a medication, see the estradiol (medication)
article.

Biological function

Sexual development

The development of

epiphyseal closure (thereby limiting final height) in both sexes.[11][12]

Reproduction

Female reproductive system

In the female, estradiol acts as a growth hormone for tissue of the reproductive organs, supporting the lining of the

implantation. During pregnancy, estradiol increases due to placental production. 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.[citation needed] 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.[citation needed
]

Male reproductive system

The effect of estradiol (and estrogens in general) 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.[14] It functions (in vitro) to prevent apoptosis of male sperm cells.[15] While some studies in the early 1990s claimed a connection between globally declining

sperm counts and estrogen exposure in the environment,[16] later studies found no such connection, nor evidence of a general decline in sperm counts.[17][18]
Suppression of estradiol production in a subpopulation of subfertile men may improve the semen analysis.[19]

Males with certain

Klinefelter's syndrome, will have a higher level of estradiol.[20]

Skeletal system

Estradiol has a profound effect on bone. Individuals without it (or other estrogens) will become tall and

epiphyseal closure is delayed or may not take place.[21] Bone density is also affected, resulting in early osteopenia and osteoporosis.[22] Low levels of estradiol may also predict fractures, with post-menopausal women having the highest incidence of bone fracture.[23] Women past menopause experience an accelerated loss of bone mass due to a relative estrogen deficiency.[24]

Skin health

The

surface lipids (sebum production).[25] Along with chronological aging and photoaging, estrogen deficiency in menopause is one of the three main factors that predominantly influences skin aging.[25]

Hormone replacement therapy consisting of systemic treatment with estrogen alone or in combination with a progestogen, has well-documented and considerable beneficial effects on the skin of postmenopausal women.[25][26] These benefits include increased skin collagen content, skin thickness and elasticity, and skin hydration and surface lipids.[25][26] Topical estrogen has been found to have similar beneficial effects on the skin.[25] In addition, a study has found that topical 2% progesterone cream significantly increases skin elasticity and firmness and observably decreases wrinkles in peri- and postmenopausal women.[26] Skin hydration and surface lipids, on the other hand, did not significantly change with topical progesterone.[26] These findings suggest that progesterone, like estrogen, also has beneficial effects on the skin, and may be independently protective against skin aging.[26]

Nervous system

Estrogens can be produced in the

neuroprotective function.[27]

The positive and negative

feedback loops of the menstrual cycle involve ovarian estradiol as the link to the hypothalamic-pituitary system to regulate gonadotropins.[28]

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.[29][30]

The volumes of

prenatally
and later in 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.[32] 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.[33]

Estrogen has been found to increase the secretion of oxytocin and to increase the expression of its receptor, the oxytocin receptor, in the brain.[34] In women, a single dose of estradiol has been found to be sufficient to increase circulating oxytocin concentrations.[35]

Gynecological cancers

Estradiol has been tied to the development and progression of cancers such as breast cancer, ovarian cancer and endometrial cancer. Estradiol affects target tissues mainly by interacting with two

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.[38]

Cardiovascular system

Estrogen affects certain

coronary arteries.[39] 17-beta-estradiol (E2) is considered the most potent estrogen found in humans. E2 influences vascular function, apoptosis, and damage during cardiac ischemia and reperfusion. E2 can protect the heart and individual cardiac myocytes from injuries related to ischemia. After a heart attack or long periods of hypertension, E2 inhibits the adverse effects of pathologic remodeling of the heart.[40]

During

venous thromboembolism
.

Absolute and relative incidence of venous thromboembolism (VTE) during pregnancy and the postpartum period
Absolute incidence of first VTE per 10,000 person–years during pregnancy and the postpartum period
Swedish data A Swedish data B English data Danish data
Time period N Rate (95% CI) N Rate (95% CI) N Rate (95% CI) N Rate (95% CI)
Outside pregnancy 1105 4.2 (4.0–4.4) 1015 3.8 (?) 1480 3.2 (3.0–3.3) 2895 3.6 (3.4–3.7)
Antepartum 995 20.5 (19.2–21.8) 690 14.2 (13.2–15.3) 156 9.9 (8.5–11.6) 491 10.7 (9.7–11.6)
  Trimester 1 207 13.6 (11.8–15.5) 172 11.3 (9.7–13.1) 23 4.6 (3.1–7.0) 61 4.1 (3.2–5.2)
  Trimester 2 275 17.4 (15.4–19.6) 178 11.2 (9.7–13.0) 30 5.8 (4.1–8.3) 75 5.7 (4.6–7.2)
  Trimester 3 513 29.2 (26.8–31.9) 340 19.4 (17.4–21.6) 103 18.2 (15.0–22.1) 355 19.7 (17.7–21.9)
Around delivery 115 154.6 (128.8–185.6) 79 106.1 (85.1–132.3) 34 142.8 (102.0–199.8)
Postpartum 649 42.3 (39.2–45.7) 509 33.1 (30.4–36.1) 135 27.4 (23.1–32.4) 218 17.5 (15.3–20.0)
  Early postpartum 584 75.4 (69.6–81.8) 460 59.3 (54.1–65.0) 177 46.8 (39.1–56.1) 199 30.4 (26.4–35.0)
  Late postpartum 65 8.5 (7.0–10.9) 49 6.4 (4.9–8.5) 18 7.3 (4.6–11.6) 319 3.2 (1.9–5.0)
Incidence rate ratios (IRRs) of first VTE during pregnancy and the postpartum period
Swedish data A Swedish data B English data Danish data
Time period IRR* (95% CI) IRR* (95% CI) IRR (95% CI)† IRR (95% CI)†
Outside pregnancy
Reference (i.e., 1.00)
Antepartum 5.08 (4.66–5.54) 3.80 (3.44–4.19) 3.10 (2.63–3.66) 2.95 (2.68–3.25)
  Trimester 1 3.42 (2.95–3.98) 3.04 (2.58–3.56) 1.46 (0.96–2.20) 1.12 (0.86–1.45)
  Trimester 2 4.31 (3.78–4.93) 3.01 (2.56–3.53) 1.82 (1.27–2.62) 1.58 (1.24–1.99)
  Trimester 3 7.14 (6.43–7.94) 5.12 (4.53–5.80) 5.69 (4.66–6.95) 5.48 (4.89–6.12)
Around delivery 37.5 (30.9–44.45) 27.97 (22.24–35.17) 44.5 (31.68–62.54)
Postpartum 10.21 (9.27–11.25) 8.72 (7.83–9.70) 8.54 (7.16–10.19) 4.85 (4.21–5.57)
  Early postpartum 19.27 (16.53–20.21) 15.62 (14.00–17.45) 14.61 (12.10–17.67) 8.44 (7.27–9.75)
  Late postpartum 2.06 (1.60–2.64) 1.69 (1.26–2.25) 2.29 (1.44–3.65) 0.89 (0.53–1.39)
Notes: Swedish data A = Using any code for VTE regardless of confirmation. Swedish data B = Using only algorithm-confirmed VTE. Early postpartum = First 6 weeks after delivery. Late postpartum = More than 6 weeks after delivery. * = Adjusted for age and calendar year. † = Unadjusted ratio calculated based on the data provided. Source: [41]

Other functions

Estradiol has complex effects on the

blood clotting.[citation needed] In high amounts, estradiol can lead to cholestasis, for instance cholestasis of pregnancy
.

Certain gynecological conditions are dependent on estrogen, such as

]

Biological activity

Estradiol acts primarily as an

affinities for other endogenous estrogens, such as estrone and estriol.[43] Additional mERs besides GPER include ER-X, ERx, and Gq-mER.[44][45]

ERα/ERβ are in inactive state trapped in multimolecular chaperone complexes organized around the heat shock protein 90 (HSP90), containing p23 protein, and immunophilin, and located in majority in cytoplasm and partially in nucleus. In the E2 classical pathway or estrogen classical pathway, estradiol enters the

estrogen response element
, ERE), allowing for gene transcription which can take place over hours and days.

Given by

subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol.[46][47][48] As such, estradiol is the main estrogen in the body, although the roles of estrone and estriol as estrogens are said not to be negligible.[48]

Selected biological properties of endogenous estrogens in rats
Estrogen
RBA
Tooltip relative binding affinity (%)
Uterine weight (%)
Uterotrophy
LHTooltip Luteinizing hormone levels (%)
RBA
Tooltip relative binding affinity (%)
Control 100 100
Estradiol (E2) 100 506 ± 20 +++ 12–19 100
Estrone (E1) 11 ± 8 490 ± 22 +++ ? 20
Estriol (E3) 10 ± 4 468 ± 30 +++ 8–18 3
Estetrol (E4) 0.5 ± 0.2 ? Inactive ? 1
17α-Estradiol 4.2 ± 0.8 ? ? ? ?
2-Hydroxyestradiol 24 ± 7 285 ± 8 +b 31–61 28
2-Methoxyestradiol 0.05 ± 0.04 101 Inactive ? 130
4-Hydroxyestradiol 45 ± 12 ? ? ? ?
4-Methoxyestradiol 1.3 ± 0.2 260 ++ ? 9
4-Fluoroestradiola 180 ± 43 ? +++ ? ?
2-Hydroxyestrone 1.9 ± 0.8 130 ± 9 Inactive 110–142 8
2-Methoxyestrone 0.01 ± 0.00 103 ± 7 Inactive 95–100 120
4-Hydroxyestrone 11 ± 4 351 ++ 21–50 35
4-Methoxyestrone 0.13 ± 0.04 338 ++ 65–92 12
16α-Hydroxyestrone 2.8 ± 1.0 552 ± 42 +++ 7–24 <0.5
2-Hydroxyestriol 0.9 ± 0.3 302 +b ? ?
2-Methoxyestriol 0.01 ± 0.00 ? Inactive ? 4
Notes: Values are mean ± SD or range. ER RBA =
endogenous
). b = Atypical uterotrophic effect which plateaus within 48 hours (estradiol's uterotrophy continues linearly up to 72 hours). Sources: See template.

Biochemistry

steroidogenesis, showing estradiol at bottom right.[49]

Biosynthesis

Estradiol, like other

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-HSD. Smaller amounts of estradiol are also produced by the adrenal cortex, and, in men, by the testes.[medical citation needed]

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.[51] Estradiol is also produced in the brain and in arterial walls.

In men, approximately 15 to 25% of circulating estradiol is produced in the testicles.[52][53] The rest is synthesized via peripheral aromatization of testosterone into estradiol and of androstenedione into estrone (which is then transformed into estradiol via peripheral 17β-HSD).[52][53] This peripheral aromatization occurs predominantly in adipose tissue, but also occurs in other tissues such as bone, liver, and the brain.[52] Approximately 40 to 50 µg of estradiol is produced per day in men.[52]

Distribution

In plasma, estradiol is largely bound to SHBG and albumin. Only about 2.21% (± 0.04%) of estradiol is free and biologically active. The percentage remains constant throughout the menstrual cycle.[54]

Metabolism

Metabolic pathways of estradiol in humans
The image above contains clickable links
Description: The
hydroxyl (–OH) groups
. Sources: See template page.

Inactivation of estradiol includes conversion to less-active estrogens, such as estrone and estriol. Estriol is the major urinary

conjugated in the liver to form estrogen conjugates like estradiol sulfate, estradiol glucuronide 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.

Estradiol is also metabolized via

metabolic transformations also being involved.[56]

Estradiol is additionally

conjugated with an ester into lipoidal estradiol forms like estradiol palmitate and estradiol stearate to a certain extent; these esters are stored in adipose tissue and may act as a very long-lasting reservoir of estradiol.[57][58]

Excretion

Estradiol is

Enterohepatic recirculation causes a delay in excretion of estradiol.[59]

Levels

Estradiol levels across the menstrual cycle in 36 normally cycling, ovulatory women, based on 956 specimens.[61] The horizontal dashed lines are the mean integrated levels for each curve. The vertical dashed line in the center is mid-cycle.

Levels of estradiol in premenopausal women are highly variable throughout the menstrual cycle and reference ranges widely vary from source to source.[62] Estradiol levels are minimal and according to most laboratories range from 20 to 80 pg/mL during the early to mid follicular phase (or the first week of the menstrual cycle, also known as menses).[63][64] Levels of estradiol gradually increase during this time and through the mid to late follicular phase (or the second week of the menstrual cycle) until the pre-ovulatory phase.[62][63] At the time of pre-ovulation (a period of about 24 to 48 hours), estradiol levels briefly surge and reach their highest concentrations of any other time during the menstrual cycle.[62] Circulating levels are typically between 130 and 200 pg/mL at this time, but in some women may be as high as 300 to 400 pg/mL, and the upper limit of the reference range of some laboratories are even greater (for instance, 750 pg/mL).[62][63][65][66][67] Following ovulation (or mid-cycle) and during the latter half of the menstrual cycle or the luteal phase, estradiol levels plateau and fluctuate between around 100 and 150 pg/mL during the early and mid luteal phase, and at the time of the late luteal phase, or a few days before menstruation, reach a low of around 40 pg/mL.[62][64] The mean integrated levels of estradiol during a full menstrual cycle have variously been reported by different sources as 80, 120, and 150 pg/mL.[64][68][69] Although contradictory reports exist, one study found mean integrated estradiol levels of 150 pg/mL in younger women whereas mean integrated levels ranged from 50 to 120 pg/mL in older women.[69]

During the reproductive years of human females, levels of estradiol 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.[

postmenopausal women (14–55 versus <35 pg/mL, respectively).[citation needed] It has also been reported that if concentrations of estradiol in a 70-year-old man are compared to those of a 70-year-old woman, levels are approximately 2- to 4-fold higher in the man.[70]

Endogenous estradiol production rates and plasma estrogen levels
Group E2 (prod) E2 (levels) E1 (levels) Ratio
Pubertal girlsa
  Tanner stage I (childhood)
  Tanner stage II (ages 8–12)
  Tanner stage III (ages 10–13)
  Tanner stage IV (ages 11–14)
  Tanner stage V (ages 12–15)
    Follicular (days 1–14)
    Luteal (days 15–28)
 
?
?
?
?
 
?
?
 
9 (<9–20) pg/mL
15 (<9–30) pg/mL
27 (<9–60) pg/mL
55 (16–85) pg/mL
 
50 (30–100) pg/mL
130 (70–300) pg/mL
 
13 (<9–23) pg/mL
18 (10–37) pg/mL
26 (17–58) pg/mL
36 (23–69) pg/mL
 
44 (30–89) pg/mL
75 (39–160) pg/mL
 
?
?
?
?
 
?
?
Prepubertal
boys
? 2–8 pg/mL ? ?
Oral contraceptive (anovulatory
)
 
30–100 µg/day
100–160 µg/day
320–640 µg/day
300 µg/day
?
 
40–60 pg/mL
60–100 pg/mL
200–400 pg/mL
190 pg/mL
12–50 pg/mL
 
40–60 pg/mL
?
170–200 pg/mL
100–150 pg/mL
?
 
0.5–1
?
1–2
1.5
?
Postmenopausal women 18 µg/day 5–20 pg/mL 30–70 pg/mL 0.3–0.8
Third trimester
(weeks 27–40)
 
?
?
?
 
1,000–5,000 pg/mL
5,000–15,000 pg/mL
10,000–40,000 pg/mL
 
?
?
?
 
?
?
?
Mena 20–60 µg/day 27 (20–55) pg/mL 20–90 pg/mL 0.4–0.6
Footnotes: a = Format is "mean value (range)" or just "range". Sources: [71][72][73][74][75][61][76]

Measurement

In women, serum estradiol is measured in a

clinical laboratory and reflects primarily the activity of the ovaries. The Estradiol blood test measures the amount of estradiol in the blood.[77] It is used to check the function of the ovaries, placenta, adrenal glands.[77] This can detect 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.

Ranges

Individual laboratory results should always be 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 male 50[78] 200[78] pmol/L
14 55 pg/mL
Adult female (follicular
phase
, day 5)
70[78]
95% PI (standard)
500[78]
95% PI
pmol/L
110[79]
90% PI (used
in diagram)
220[79]
90% PI
19 (95% PI) 140 (95% PI) pg/mL
30 (90% PI) 60 (90% PI)
Adult female (
preovulatory

peak)
400[78] 1500[78] pmol/L
110 410 pg/mL
Adult female
(luteal phase)
70[78] 600[78] pmol/L
19 160 pg/mL
Adult female – free
(not protein bound)
0.5[80][original research?] 9[80][original research?] pg/mL
1.7[80][original research?] 33[80][original research?] pmol/L
Post-menopausal female N/A[78] < 130[78] pmol/L
N/A < 35 pg/mL
Reference ranges for the blood content of estradiol during the menstrual cycle
Reference ranges for the blood content of estradiol during the menstrual cycle
- The ranges denoted By biological stage may be used in closely monitored menstrual cycles in regard to other markers of its biological progression, with the time scale being compressed or stretched to how much faster or slower, respectively, the cycle progresses compared to an average cycle.
- The ranges denoted Inter-cycle variability are more appropriate to use in unmonitored cycles with only the beginning of menstruation known, but where the woman accurately knows her average cycle lengths and time of ovulation, and that they are somewhat averagely regular, with the time scale being compressed or stretched to how much a woman's average cycle length is shorter or longer, respectively, than the average of the population.
- The ranges denoted Inter-woman variability are more appropriate to use when the average cycle lengths and time of ovulation are unknown, but only the beginning of menstruation is given.[81]

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.

During pregnancy, estrogen levels, including estradiol, rise steadily toward term. The source of these estrogens is the placenta, which aromatizes prohormones produced in the fetal adrenal gland.

Production rates, secretion rates, clearance rates, and blood levels of major sex hormones
Sex Sex hormone Reproductive
phase
Blood
production rate
Gonadal
secretion rate
Metabolic
clearance rate
Reference range (serum levels)
SI units Non-SI units
Men Androstenedione
2.8 mg/day 1.6 mg/day 2200 L/day 2.8–7.3 nmol/L 80–210 ng/dL
Testosterone
6.5 mg/day 6.2 mg/day 950 L/day 6.9–34.7 nmol/L 200–1000 ng/dL
Estrone
150 μg/day 110 μg/day 2050 L/day 37–250 pmol/L 10–70 pg/mL
Estradiol
60 μg/day 50 μg/day 1600 L/day <37–210 pmol/L 10–57 pg/mL
Estrone sulfate
80 μg/day Insignificant 167 L/day 600–2500 pmol/L 200–900 pg/mL
Women Androstenedione
3.2 mg/day 2.8 mg/day 2000 L/day 3.1–12.2 nmol/L 89–350 ng/dL
Testosterone
190 μg/day 60 μg/day 500 L/day 0.7–2.8 nmol/L 20–81 ng/dL
Estrone Follicular phase 110 μg/day 80 μg/day 2200 L/day 110–400 pmol/L 30–110 pg/mL
Luteal phase 260 μg/day 150 μg/day 2200 L/day 310–660 pmol/L 80–180 pg/mL
Postmenopause 40 μg/day Insignificant 1610 L/day 22–230 pmol/L 6–60 pg/mL
Estradiol Follicular phase 90 μg/day 80 μg/day 1200 L/day <37–360 pmol/L 10–98 pg/mL
Luteal phase 250 μg/day 240 μg/day 1200 L/day 699–1250 pmol/L 190–341 pg/mL
Postmenopause 6 μg/day Insignificant 910 L/day <37–140 pmol/L 10–38 pg/mL
Estrone sulfate Follicular phase 100 μg/day Insignificant 146 L/day 700–3600 pmol/L 250–1300 pg/mL
Luteal phase 180 μg/day Insignificant 146 L/day 1100–7300 pmol/L 400–2600 pg/mL
Progesterone Follicular phase 2 mg/day 1.7 mg/day 2100 L/day 0.3–3 nmol/L 0.1–0.9 ng/mL
Luteal phase 25 mg/day 24 mg/day 2100 L/day 19–45 nmol/L 6–14 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.

Medical use

Estradiol is used as a

symptoms as well as feminizing hormone therapy for trans individuals.[82]

Chemistry

Structures of major endogenous estrogens
Chemical structures of major endogenous estrogens
Estrone (E1)
Estradiol (E2)
Estriol (E3)

Estradiol is an

hydroxyl groups, one at the C3 position and the other at the 17β position, as well as three double bonds in the A ring. Due to its two hydroxyl groups, estradiol is often abbreviated as E2. The structurally related estrogens, estrone (E1), estriol (E3), and estetrol
(E4) have one, three, and four hydroxyl groups, respectively.

Neuropsychopharmacology

In a randomized, double-blind, placebo-controlled study, estradiol was shown to have gender-specific effects on fairness sensitivity. Overall, when the division of a given amount of money was framed as either fair or unfair in a modified version of the ultimatum game, estradiol increased the acceptance rate of fair-framed proposals among men and decreased it among women. However, among the placebo-group "the mere belief of receiving estradiol treatment significantly increased the acceptance of unfair-framed offers in both sexes", indicating that so-called "environmental" factors played a role in organising the responses towards these presentations of the ultimatum game.[83]

History

The discovery of estrogen is usually credited to the

sexual maturation and reproduction.[84][85][86] At the time of its discovery, Allen and Doisy did not name the hormone, and simply referred to it as an "ovarian hormone" or "follicular hormone";[85] others referred to it variously as feminin, folliculin, menformon, thelykinin, and emmenin.[87][88] In 1926, Parkes and Bellerby coined the term estrin to describe the hormone on the basis of it inducing estrus in animals.[89][87] Estrone was isolated and purified independently by Allen and Doisy and German scientist Adolf Butenandt in 1929, and estriol was isolated and purified by Marrian in 1930; they were the first estrogens to be identified.[85][90][91]

Estradiol, the most potent of the three major estrogens, was the last of the three to be identified.

partial synthesis of estradiol from cholesterol was developed by Inhoffen and Hohlweg in 1940, and a total synthesis was developed by Anner and Miescher in 1948.[85]

Society and culture

Etymology

The name estradiol derives from estra-,

.

References

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  61. ^ a b http://www.ilexmedical.com/files/PDF/Estradiol_ARC.pdf[bare URL PDF]
  62. ^ . Estradiol levels are minimal during the earliest days of the follicular phase, but increasing concentrations are released into the general circulation as the follicle matures. The highest levels are reached about 24 to 48 hours before the LH peak. In fact, the pre-ovulatory peak in estradiol represents its highest concentration during the entire menstrual cycle. Serum concentrations at this time are typically about 130–200 pg/mL, but concentrations as high as 300–400 pg/mL can be achieved in some women. Following a transient fall in association with ovulation, estradiol secretion is restored by production from the corpus luteum during the luteal phase. Plateau levels of around 100–150 pg/mL (Abraham, 1978; Thorneycroft et al., 1971) are most often seen during the period from −10 to −5 days before the onset of menses. With the regression of the corpus luteum, estradiol levels fall, gradually in some women and precipitously in others, during the last few days of the luteal phase. This ushers in the onset of menses, the sloughing of the endometrium. Serum estradiol during menses is approximately 30–50 pg/mL. (Source.)
  63. ^ . In most laboratories, serum estradiol levels range from 20 to 80 pg/mL during the early to midfollicular phase of the menstrual cycle and peak at 200 to 500 pg/mL during the preovulatory surge. During the midluteal phase, serum estradiol levels range from 60 to 200 pg/mL.
  64. ^ . Plasma levels of estradiol range from 40 to 80 pg/ml during the 1st week of the ovarian cycle (early follicular phase) and from 80 to 300 pg/ml during the 2nd week (mid- and late follicular phase including periovulatory peak). Then during the 3rd and 4th weeks, estradiol fluctuates between 100 and 150 pg/ml (early and mid-luteal phase) to 40 pg/ml a few days before menstruation (late luteal phase). The mean integrated estradiol level during a full 28-day normal cycle is around 80 pg/ml.
  65. . Midcycle: 150-750 pg/mL
  66. . Mid-cycle: 110-330 pg/mL
  67. . Ovulatory: 200-400 pg/mL
  68. . [...] following the menopause, circulating estradiol levels decrease from a premenopausal mean of 120 pg/ml to only 13 pg/ml.
  69. ^ . [...] [premenopausal] mean [estradiol] concentration of 150 pg/ml [...]
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  77. ^ a b "Estradiol blood test: MedlinePlus Medical Encyclopedia". medlineplus.gov. Retrieved 6 May 2019.
  78. ^ a b c d e f g h i j GPNotebook — reference range (oestradiol) Retrieved on 27 September 2009
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