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Estrogen
Estrogen ester
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    Estrogen ester

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    Not to be confused with Esterified estrogens or Conjugated estrogens.

    An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens such as estrone, estriol, and even nonsteroidal estrogens like diethylstilbestrol. Esterification renders estradiol into a prodrug of estradiol with increased resistance to first-pass metabolism, slightly improving its oral bioavailability. In addition, estrogen esters have increased lipophilicity, which results in a longer duration when given by intramuscular or subcutaneous injection due to the formation of a long-lasting local depot in muscle and fat. Conversely, this is not the case with intravenous injection or oral administration. Estrogen esters are rapidly hydrolyzed into their parent estrogen by esterases once they have been released from the depot. Because estradiol esters are prodrugs of estradiol, they are considered to be natural and bioidentical forms of estrogen.

    Estrogen esters are used in hormone therapy, hormonal contraception, and high-dose estrogen therapy (e.g., for prostate cancer and breast cancer), among other indications. The first estrogen ester to be marketed was estradiol benzoate in 1933, which was followed by many more. One of the most widely used estradiol esters is estradiol valerate, which was first introduced in 1954. Other major estradiol esters that are or have been used in medicine include estradiol acetate, estradiol cypionate, estradiol dipropionate, estradiol enantate, estradiol undecylate, and polyestradiol phosphate (an estrogen ester polymer), as well as the nitrogen mustard alkylating antineoplastic agent estramustine phosphate (estradiol normustine phosphate).

    The most common vehicles for injections of steroids and steroid esters are oil solutions, but aqueous solutions, aqueous suspensions, and emulsions have also been used. The durations of estrogen esters are not prolonged if they are given orally, vaginally, or by intravenous injection.

    Pharmacology

    Estrogen esters are essentially inactive themselves, with esters such as estradiol valerate and estradiol sulfate having about 2% of the affinity of estradiol for the estrogen receptor. Likewise, the estrogen ether mestranol (ethinylestradiol 3-methyl ether) has about 1% of the affinity of estradiol for the estrogen receptor.Estrone sulfate has less than 1% of the affinity of estradiol for the estrogen receptor. As such, estrogen esters do not bind to the estrogen receptor except at extremely high concentrations. The residual affinity of estrogen esters for the estrogen receptor in bioassays may actually be due to conversion into the parent estrogen, as attempts to prevent or limit this conversion have been found to abolish binding to the estrogen receptor and estrogenicity.

    Affinities of estrogen receptor ligands for the ERα and ERβ
    Ligand Other names Relative binding affinities (RBA, %)a Absolute binding affinities (Ki, nM)a Action
    ERα ERβ ERα ERβ
    Estradiol E2; 17β-Estradiol 100 100 0.115 (0.04–0.24) 0.15 (0.10–2.08) Estrogen
    Estrone E1; 17-Ketoestradiol 16.39 (0.7–60) 6.5 (1.36–52) 0.445 (0.3–1.01) 1.75 (0.35–9.24) Estrogen
    Estriol E3; 16α-OH-17β-E2 12.65 (4.03–56) 26 (14.0–44.6) 0.45 (0.35–1.4) 0.7 (0.63–0.7) Estrogen
    Estetrol E4; 15α,16α-Di-OH-17β-E2 4.0 3.0 4.9 19 Estrogen
    Alfatradiol 17α-Estradiol 20.5 (7–80.1) 8.195 (2–42) 0.2–0.52 0.43–1.2 Metabolite
    16-Epiestriol 16β-Hydroxy-17β-estradiol 7.795 (4.94–63) 50 ? ? Metabolite
    17-Epiestriol 16α-Hydroxy-17α-estradiol 55.45 (29–103) 79–80 ? ? Metabolite
    16,17-Epiestriol 16β-Hydroxy-17α-estradiol 1.0 13 ? ? Metabolite
    2-Hydroxyestradiol 2-OH-E2 22 (7–81) 11–35 2.5 1.3 Metabolite
    2-Methoxyestradiol 2-MeO-E2 0.0027–2.0 1.0 ? ? Metabolite
    4-Hydroxyestradiol 4-OH-E2 13 (8–70) 7–56 1.0 1.9 Metabolite
    4-Methoxyestradiol 4-MeO-E2 2.0 1.0 ? ? Metabolite
    2-Hydroxyestrone 2-OH-E1 2.0–4.0 0.2–0.4 ? ? Metabolite
    2-Methoxyestrone 2-MeO-E1 <0.001–<1 <1 ? ? Metabolite
    4-Hydroxyestrone 4-OH-E1 1.0–2.0 1.0 ? ? Metabolite
    4-Methoxyestrone 4-MeO-E1 <1 <1 ? ? Metabolite
    16α-Hydroxyestrone 16α-OH-E1; 17-Ketoestriol 2.0–6.5 35 ? ? Metabolite
    2-Hydroxyestriol 2-OH-E3 2.0 1.0 ? ? Metabolite
    4-Methoxyestriol 4-MeO-E3 1.0 1.0 ? ? Metabolite
    Estradiol sulfate E2S; Estradiol 3-sulfate <1 <1 ? ? Metabolite
    Estradiol disulfate Estradiol 3,17β-disulfate 0.0004 ? ? ? Metabolite
    Estradiol 3-glucuronide E2-3G 0.0079 ? ? ? Metabolite
    Estradiol 17β-glucuronide E2-17G 0.0015 ? ? ? Metabolite
    Estradiol 3-gluc. 17β-sulfate E2-3G-17S 0.0001 ? ? ? Metabolite
    Estrone sulfate E1S; Estrone 3-sulfate <1 <1 >10 >10 Metabolite
    Estradiol benzoate EB; Estradiol 3-benzoate 10 ? ? ? Estrogen
    Estradiol 17β-benzoate E2-17B 11.3 32.6 ? ? Estrogen
    Estrone methyl ether Estrone 3-methyl ether 0.145 ? ? ? Estrogen
    ent-Estradiol 1-Estradiol 1.31–12.34 9.44–80.07 ? ? Estrogen
    Equilin 7-Dehydroestrone 13 (4.0–28.9) 13.0–49 0.79 0.36 Estrogen
    Equilenin 6,8-Didehydroestrone 2.0–15 7.0–20 0.64 0.62 Estrogen
    17β-Dihydroequilin 7-Dehydro-17β-estradiol 7.9–113 7.9–108 0.09 0.17 Estrogen
    17α-Dihydroequilin 7-Dehydro-17α-estradiol 18.6 (18–41) 14–32 0.24 0.57 Estrogen
    17β-Dihydroequilenin 6,8-Didehydro-17β-estradiol 35–68 90–100 0.15 0.20 Estrogen
    17α-Dihydroequilenin 6,8-Didehydro-17α-estradiol 20 49 0.50 0.37 Estrogen
    Δ8-Estradiol 8,9-Dehydro-17β-estradiol 68 72 0.15 0.25 Estrogen
    Δ8-Estrone 8,9-Dehydroestrone 19 32 0.52 0.57 Estrogen
    Ethinylestradiol EE; 17α-Ethynyl-17β-E2 120.9 (68.8–480) 44.4 (2.0–144) 0.02–0.05 0.29–0.81 Estrogen
    Mestranol EE 3-methyl ether ? 2.5 ? ? Estrogen
    Moxestrol RU-2858; 11β-Methoxy-EE 35–43 5–20 0.5 2.6 Estrogen
    Methylestradiol 17α-Methyl-17β-estradiol 70 44 ? ? Estrogen
    Diethylstilbestrol DES; Stilbestrol 129.5 (89.1–468) 219.63 (61.2–295) 0.04 0.05 Estrogen
    Hexestrol Dihydrodiethylstilbestrol 153.6 (31–302) 60–234 0.06 0.06 Estrogen
    Dienestrol Dehydrostilbestrol 37 (20.4–223) 56–404 0.05 0.03 Estrogen
    Benzestrol (B2) – 114 ? ? ? Estrogen
    Chlorotrianisene TACE 1.74 ? 15.30 ? Estrogen
    Triphenylethylene TPE 0.074 ? ? ? Estrogen
    Triphenylbromoethylene TPBE 2.69 ? ? ? Estrogen
    Tamoxifen ICI-46,474 3 (0.1–47) 3.33 (0.28–6) 3.4–9.69 2.5 SERM
    Afimoxifene 4-Hydroxytamoxifen; 4-OHT 100.1 (1.7–257) 10 (0.98–339) 2.3 (0.1–3.61) 0.04–4.8 SERM
    Toremifene 4-Chlorotamoxifen; 4-CT ? ? 7.14–20.3 15.4 SERM
    Clomifene MRL-41 25 (19.2–37.2) 12 0.9 1.2 SERM
    Cyclofenil F-6066; Sexovid 151–152 243 ? ? SERM
    Nafoxidine U-11,000A 30.9–44 16 0.3 0.8 SERM
    Raloxifene – 41.2 (7.8–69) 5.34 (0.54–16) 0.188–0.52 20.2 SERM
    Arzoxifene LY-353,381 ? ? 0.179 ? SERM
    Lasofoxifene CP-336,156 10.2–166 19.0 0.229 ? SERM
    Ormeloxifene Centchroman ? ? 0.313 ? SERM
    Levormeloxifene 6720-CDRI; NNC-460,020 1.55 1.88 ? ? SERM
    Ospemifene Deaminohydroxytoremifene 0.82–2.63 0.59–1.22 ? ? SERM
    Bazedoxifene – ? ? 0.053 ? SERM
    Etacstil GW-5638 4.30 11.5 ? ? SERM
    ICI-164,384 – 63.5 (3.70–97.7) 166 0.2 0.08 Antiestrogen
    Fulvestrant ICI-182,780 43.5 (9.4–325) 21.65 (2.05–40.5) 0.42 1.3 Antiestrogen
    Propylpyrazoletriol PPT 49 (10.0–89.1) 0.12 0.40 92.8 ERα agonist
    16α-LE2 16α-Lactone-17β-estradiol 14.6–57 0.089 0.27 131 ERα agonist
    16α-Iodo-E2 16α-Iodo-17β-estradiol 30.2 2.30 ? ? ERα agonist
    Methylpiperidinopyrazole MPP 11 0.05 ? ? ERα antagonist
    Diarylpropionitrile DPN 0.12–0.25 6.6–18 32.4 1.7 ERβ agonist
    8β-VE2 8β-Vinyl-17β-estradiol 0.35 22.0–83 12.9 0.50 ERβ agonist
    Prinaberel ERB-041; WAY-202,041 0.27 67–72 ? ? ERβ agonist
    ERB-196 WAY-202,196 ? 180 ? ? ERβ agonist
    Erteberel SERBA-1; LY-500,307 ? ? 2.68 0.19 ERβ agonist
    SERBA-2 – ? ? 14.5 1.54 ERβ agonist
    Coumestrol – 9.225 (0.0117–94) 64.125 (0.41–185) 0.14–80.0 0.07–27.0 Xenoestrogen
    Genistein – 0.445 (0.0012–16) 33.42 (0.86–87) 2.6–126 0.3–12.8 Xenoestrogen
    Equol – 0.2–0.287 0.85 (0.10–2.85) ? ? Xenoestrogen
    Daidzein – 0.07 (0.0018–9.3) 0.7865 (0.04–17.1) 2.0 85.3 Xenoestrogen
    Biochanin A – 0.04 (0.022–0.15) 0.6225 (0.010–1.2) 174 8.9 Xenoestrogen
    Kaempferol – 0.07 (0.029–0.10) 2.2 (0.002–3.00) ? ? Xenoestrogen
    Naringenin – 0.0054 (<0.001–0.01) 0.15 (0.11–0.33) ? ? Xenoestrogen
    8-Prenylnaringenin 8-PN 4.4 ? ? ? Xenoestrogen
    Quercetin – <0.001–0.01 0.002–0.040 ? ? Xenoestrogen
    Ipriflavone – <0.01 <0.01 ? ? Xenoestrogen
    Miroestrol – 0.39 ? ? ? Xenoestrogen
    Deoxymiroestrol – 2.0 ? ? ? Xenoestrogen
    β-Sitosterol – <0.001–0.0875 <0.001–0.016 ? ? Xenoestrogen
    Resveratrol – <0.001–0.0032 ? ? ? Xenoestrogen
    α-Zearalenol – 48 (13–52.5) ? ? ? Xenoestrogen
    β-Zearalenol – 0.6 (0.032–13) ? ? ? Xenoestrogen
    Zeranol α-Zearalanol 48–111 ? ? ? Xenoestrogen
    Taleranol β-Zearalanol 16 (13–17.8) 14 0.8 0.9 Xenoestrogen
    Zearalenone ZEN 7.68 (2.04–28) 9.45 (2.43–31.5) ? ? Xenoestrogen
    Zearalanone ZAN 0.51 ? ? ? Xenoestrogen
    Bisphenol A BPA 0.0315 (0.008–1.0) 0.135 (0.002–4.23) 195 35 Xenoestrogen
    Endosulfan EDS <0.001–<0.01 <0.01 ? ? Xenoestrogen
    Kepone Chlordecone 0.0069–0.2 ? ? ? Xenoestrogen
    o,p'-DDT – 0.0073–0.4 ? ? ? Xenoestrogen
    p,p'-DDT – 0.03 ? ? ? Xenoestrogen
    Methoxychlor p,p'-Dimethoxy-DDT 0.01 (<0.001–0.02) 0.01–0.13 ? ? Xenoestrogen
    HPTE Hydroxychlor; p,p'-OH-DDT 1.2–1.7 ? ? ? Xenoestrogen
    Testosterone T; 4-Androstenolone <0.0001–<0.01 <0.002–0.040 >5000 >5000 Androgen
    Dihydrotestosterone DHT; 5α-Androstanolone 0.01 (<0.001–0.05) 0.0059–0.17 221–>5000 73–1688 Androgen
    Nandrolone 19-Nortestosterone; 19-NT 0.01 0.23 765 53 Androgen
    Dehydroepiandrosterone DHEA; Prasterone 0.038 (<0.001–0.04) 0.019–0.07 245–1053 163–515 Androgen
    5-Androstenediol A5; Androstenediol 6 17 3.6 0.9 Androgen
    4-Androstenediol – 0.5 0.6 23 19 Androgen
    4-Androstenedione A4; Androstenedione <0.01 <0.01 >10000 >10000 Androgen
    3α-Androstanediol 3α-Adiol 0.07 0.3 260 48 Androgen
    3β-Androstanediol 3β-Adiol 3 7 6 2 Androgen
    Androstanedione 5α-Androstanedione <0.01 <0.01 >10000 >10000 Androgen
    Etiocholanedione 5β-Androstanedione <0.01 <0.01 >10000 >10000 Androgen
    Methyltestosterone 17α-Methyltestosterone <0.0001 ? ? ? Androgen
    Ethinyl-3α-androstanediol 17α-Ethynyl-3α-adiol 4.0 <0.07 ? ? Estrogen
    Ethinyl-3β-androstanediol 17α-Ethynyl-3β-adiol 50 5.6 ? ? Estrogen
    Progesterone P4; 4-Pregnenedione <0.001–0.6 <0.001–0.010 ? ? Progestogen
    Norethisterone NET; 17α-Ethynyl-19-NT 0.085 (0.0015–<0.1) 0.1 (0.01–0.3) 152 1084 Progestogen
    Norethynodrel 5(10)-Norethisterone 0.5 (0.3–0.7) <0.1–0.22 14 53 Progestogen
    Tibolone 7α-Methylnorethynodrel 0.5 (0.45–2.0) 0.2–0.076 ? ? Progestogen
    Δ4-Tibolone 7α-Methylnorethisterone 0.069–<0.1 0.027–<0.1 ? ? Progestogen
    3α-Hydroxytibolone – 2.5 (1.06–5.0) 0.6–0.8 ? ? Progestogen
    3β-Hydroxytibolone – 1.6 (0.75–1.9) 0.070–0.1 ? ? Progestogen
    Footnotes: a = (1) Binding affinity values are of the format "median (range)" (# (#–#)), "range" (#–#), or "value" (#) depending on the values available. The full sets of values within the ranges can be found in the Wiki code. (2) Binding affinities were determined via displacement studies in a variety of in-vitro systems with labeled estradiol and human ERα and ERβ proteins (except the ERβ values from Kuiper et al. (1997), which are rat ERβ). Sources: See template page.
    Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors
    Estrogen Other names RBA (%)a REP (%)b
    ER ERα ERβ
    Estradiol E2 100 100 100
    Estradiol 3-sulfate E2S; E2-3S ? 0.02 0.04
    Estradiol 3-glucuronide E2-3G ? 0.02 0.09
    Estradiol 17β-glucuronide E2-17G ? 0.002 0.0002
    Estradiol benzoate EB; Estradiol 3-benzoate 10 1.1 0.52
    Estradiol 17β-acetate E2-17A 31–45 24 ?
    Estradiol diacetate EDA; Estradiol 3,17β-diacetate ? 0.79 ?
    Estradiol propionate EP; Estradiol 17β-propionate 19–26 2.6 ?
    Estradiol valerate EV; Estradiol 17β-valerate 2–11 0.04–21 ?
    Estradiol cypionate EC; Estradiol 17β-cypionate ?c 4.0 ?
    Estradiol palmitate Estradiol 17β-palmitate 0 ? ?
    Estradiol stearate Estradiol 17β-stearate 0 ? ?
    Estrone E1; 17-Ketoestradiol 11 5.3–38 14
    Estrone sulfate E1S; Estrone 3-sulfate 2 0.004 0.002
    Estrone glucuronide E1G; Estrone 3-glucuronide ? <0.001 0.0006
    Ethinylestradiol EE; 17α-Ethynylestradiol 100 17–150 129
    Mestranol EE 3-methyl ether 1 1.3–8.2 0.16
    Quinestrol EE 3-cyclopentyl ether ? 0.37 ?
    Footnotes: a = Relative binding affinities (RBAs) were determined via in-vitro displacement of labeled estradiol from estrogen receptors (ERs) generally of rodent uterine cytosol. Estrogen esters are variably hydrolyzed into estrogens in these systems (shorter ester chain length -> greater rate of hydrolysis) and the ER RBAs of the esters decrease strongly when hydrolysis is prevented. b = Relative estrogenic potencies (REPs) were calculated from half-maximal effective concentrations (EC50) that were determined via in-vitro β‐galactosidase (β-gal) and green fluorescent protein (GFP) production assays in yeast expressing human ERα and human ERβ. Both mammalian cells and yeast have the capacity to hydrolyze estrogen esters. c = The affinities of estradiol cypionate for the ERs are similar to those of estradiol valerate and estradiol benzoate (figure). Sources: See template page.

    In general, the longer the fatty acid ester chain of an estrogen ester, the greater its lipophilicity, and the longer the duration of the estrogen ester with intramuscular injection. It has been said that, via intramuscular injection, the duration of estradiol benzoate (with an ester of length 1 carbon plus a benzene ring) is 2 to 3 days, of estradiol dipropionate (with two esters each of length 2 carbons) is 1 to 2 weeks, of estradiol valerate (ester of 5 carbons) is 1 to 3 weeks, and of estradiol cypionate (ester of 3 carbons plus a cyclopentane ring) is 3 to 4 weeks. Estradiol enantate (ester of 7 carbons) has a duration of around 20 days. Likewise, estradiol undecylate (ester of 10 carbons) has a very extended duration, which is longer than that of all of the aforementioned esters.

    Pharmacokinetics of three estradiol esters by intramuscular injection
    Estrogen Dose Cmax Tmax Duration
    Estradiol benzoate 5 mg E2: 940 pg/mL
    E1: 343 pg/mL    		 E2: 1.8 days
    E1: 2.4 days    		 4–5 days
    Estradiol valerate 5 mg E2: 667 pg/mL
    E1: 324 pg/mL    		 E2: 2.2 days
    E1: 2.7 days    		 7–8 days
    Estradiol cypionate 5 mg E2: 338 pg/mL
    E1: 145 pg/mL    		 E2: 3.9 days
    E1: 5.1 days    		 11 days
    Notes: All via i.m. injection of oil solution. Determinations via radioimmunoassay with chromatographic separation. Sources: See template.
    Potencies and durations of natural estrogens by intramuscular injection
    Estrogen Form Dose (mg) Duration by dose (mg)
    EPD CICD
    Estradiol Aq. soln. ? – <1 d
    Oil soln. 40–60 – 1–2 ≈ 1–2 d
    Aq. susp. ? 3.5 0.5–2 ≈ 2–7 d; 3.5 ≈ >5 d
    Microsph. ? – 1 ≈ 30 d
    Estradiol benzoate Oil soln. 25–35 – 1.66 ≈ 2–3 d; 5 ≈ 3–6 d
    Aq. susp. 20 – 10 ≈ 16–21 d
    Emulsion ? – 10 ≈ 14–21 d
    Estradiol dipropionate Oil soln. 25–30 – 5 ≈ 5–8 d
    Estradiol valerate Oil soln. 20–30 5 5 ≈ 7–8 d; 10 ≈ 10–14 d;
    40 ≈ 14–21 d; 100 ≈ 21–28 d
    Estradiol benz. butyrate Oil soln. ? 10 10 ≈ 21 d
    Estradiol cypionate Oil soln. 20–30 – 5 ≈ 11–14 d
    Aq. susp. ? 5 5 ≈ 14–24 d
    Estradiol enanthate Oil soln. ? 5–10 10 ≈ 20–30 d
    Estradiol dienanthate Oil soln. ? – 7.5 ≈ >40 d
    Estradiol undecylate Oil soln. ? – 10–20 ≈ 40–60 d;
    25–50 ≈ 60–120 d
    Polyestradiol phosphate Aq. soln. 40–60 – 40 ≈ 30 d; 80 ≈ 60 d;
    160 ≈ 120 d
    Estrone Oil soln. ? – 1–2 ≈ 2–3 d
    Aq. susp. ? – 0.1–2 ≈ 2–7 d
    Estriol Oil soln. ? – 1–2 ≈ 1–4 d
    Polyestriol phosphate Aq. soln. ? – 50 ≈ 30 d; 80 ≈ 60 d
    Notes and sources
    Notes: All aqueous suspensions are of microcrystalline particle size. Estradiol production during the menstrual cycle is 30–640 µg/d (6.4–8.6 mg total per month or cycle). The vaginal epithelium maturation dosage of estradiol benzoate or estradiol valerate has been reported as 5 to 7 mg/week. An effective ovulation-inhibiting dose of estradiol undecylate is 20–30 mg/month. Sources: See template.

    Polyestradiol phosphate is an atypical estradiol ester. It is a phosphoric acid ester of estradiol in the form of a polymer, with an average polymer chain length of approximately 13 repeat units of estradiol phosphate. It is slowly cleaved into estradiol and phosphoric acid by phosphatases. Compared to conventional estradiol esters, polyestradiol phosphate has an extremely long duration; its elimination half-life is approximately 70 days. Whereas conventional estradiol esters form a long-lasting depot in muscle and fat at the site of injection, this is not the case with polyestradiol phosphate. Instead, polyestradiol phosphate is taken up rapidly into the bloodstream following injection (by 90% within 24 hours), where it circulates, and is accumulated in the reticuloendothelial system. Unlike other estradiol esters, polyestradiol phosphate is resistant to hydrolysis, which may be because it is a phosphatase inhibitor and may inhibit its own metabolism.

    Estrogen esters also occur naturally in the body, for instance estrogen conjugates like estrone sulfate and estrone glucuronide and the very long-lived lipoidal estradiol, which is constituted by ultra-long-chain esters like estradiol palmitate (ester of 16 carbons) and estradiol stearate (ester of 18 carbons).

    Chemistry

    Estradiol plus the fatty acid valeric acid (valerate) equals estradiol valerate, a C17β ester of estradiol and one of the most widely used estrogen esters.
    Polyestradiol phosphate, a polymer of estradiol phosphate, the C17β phosphoric acid ester of estradiol. It has on average of 13 repeat units.

    Estradiol esters have an ester moiety, usually a straight-chain fatty acid (e.g., valeric acid) or an aromatic fatty acid (e.g., benzoic acid), attached at the C3 and/or C17β positions of the steroid nucleus. These alkoxy moieties are substituted in place of the hydroxyl groups present in the unesterified estradiol molecule. Fatty acid esters serve to increase the lipophilicity of estradiol, increasing its solubility in fat. This causes them to form a depot with intramuscular or subcutaneous injection and gives them a long duration when administered by these routes.

    Some estradiol esters have other moieties instead of fatty acids as the esters. Such esters include sulfuric acid (as in estradiol sulfate), sulfamic acid (as in estradiol sulfamate), phosphoric acid (as in estradiol phosphate), glucuronic acid (as in estradiol glucuronide, and others (e.g., estramustine phosphate (estradiol 3-normustine 17β-phosphate)). These esters are all hydrophilic, and have greater water solubility than estradiol or fatty acid estradiol esters. Unlike fatty acid estradiol esters, water-soluble estradiol esters can be administered by intravenous injection.

    A few estrogen esters are polymers. These include polyestradiol phosphate and polyestriol phosphate, which are polymers of estradiol phosphate and estriol phosphate monomers, respectively. The monomers are connected in both cases by phosphate groups via the C3 and C17β positions. Polyestradiol phosphate has an average polymer chain length of approximately 13 repeat units of estradiol phosphate. That is, each polyestradiol phosphate molecule is a polymer consisting on average of 13 estradiol phosphate molecules bonded together. These polymeric estrogen esters are hydrophilic and water-soluble. Upon intramuscular injection, they do not form a depot and instead are rapidly absorbed into the circulation. However, they are only slowly cleaved into monomers, and as a result, have a very long duration in the body even outlasting that of many longer-chain fatty-acid estrogen esters.

    Chemical structures of estradiol and major estradiol esters
    Structural properties of selected estradiol esters
    Estrogen Structure Ester(s) Relative
    mol. weight     		Relative
    E2 contentb     		log Pc
    Position(s) Moiet(ies) Type Lengtha
    Estradiol
    Estradiol.svg
    		 – – – – 1.00 1.00 4.0
    Estradiol acetate
    Estradiol 3-acetate.svg
    		 C3 Ethanoic acid Straight-chain fatty acid 2 1.15 0.87 4.2
    Estradiol benzoate
    Estradiol benzoate.svg
    		 C3 Benzenecarboxylic acid Aromatic fatty acid – (~4–5) 1.38 0.72 4.7
    Estradiol dipropionate
    Estradiol dipropionate.svg
    		 C3, C17β Propanoic acid (×2) Straight-chain fatty acid 3 (×2) 1.41 0.71 4.9
    Estradiol valerate
    Estradiol valerate.svg
    		 C17β Pentanoic acid Straight-chain fatty acid 5 1.31 0.76 5.6–6.3
    Estradiol benzoate butyrate
    Estradiol butyrate benzoate.svg
    		 C3, C17β Benzoic acid, butyric acid Mixed fatty acid – (~6, 2) 1.64 0.61 6.3
    Estradiol cypionate
    Estradiol 17 beta-cypionate.svg
    		 C17β Cyclopentylpropanoic acid Aromatic fatty acid – (~6) 1.46 0.69 6.9
    Estradiol enanthate
    Estradiol enanthate.png
    		 C17β Heptanoic acid Straight-chain fatty acid 7 1.41 0.71 6.7–7.3
    Estradiol dienanthate
    Estradiol dienanthate.svg
    		 C3, C17β Heptanoic acid (×2) Straight-chain fatty acid 7 (×2) 1.82 0.55 8.1–10.4
    Estradiol undecylate
    Estradiol undecylate.svg
    		 C17β Undecanoic acid Straight-chain fatty acid 11 1.62 0.62 9.2–9.8
    Estradiol stearate
    Estradiol stearate structure.svg
    		 C17β Octadecanoic acid Straight-chain fatty acid 18 1.98 0.51 12.2–12.4
    Estradiol distearate
    Estradiol distearate.svg
    		 C3, C17β Octadecanoic acid (×2) Straight-chain fatty acid 18 (×2) 2.96 0.34 20.2
    Estradiol sulfate
    Estradiol sulfate.svg
    		 C3 Sulfuric acid Water-soluble conjugate – 1.29 0.77 0.3–3.8
    Estradiol glucuronide
    Estradiol sulfate.svg
    		 C17β Glucuronic acid Water-soluble conjugate – 1.65 0.61 2.1–2.7
    Estramustine phosphated
    Estramustine phosphate.svg
    		 C3, C17β Normustine, phosphoric acid Water-soluble conjugate – 1.91 0.52 2.9–5.0
    Polyestradiol phosphatee
    Polyestradiol phosphate.svg
    		 C3–C17β Phosphoric acid Water-soluble conjugate – 1.23f 0.81f 2.9g
    Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic fatty acids. b = Relative estradiol content by weight (i.e., relative estrogenic exposure). c = Experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). Retrieved from PubChem, ChemSpider, and DrugBank. d = Also known as estradiol normustine phosphate. e = Polymer of estradiol phosphate (~13 repeat units). f = Relative molecular weight or estradiol content per repeat unit. g = log P of repeat unit (i.e., estradiol phosphate). Sources: See individual articles.

    See also

    Further reading



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