Estradiol valerate

Source: Wikipedia, the free encyclopedia.
Estradiol valerate
subcutaneous injection
Drug classEstrogen; Estrogen ester
ATC code
Legal status
Legal status
  • US: WARNING[3]Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityOral: 3–5%[4][5]
IM injection: 100%[6][4]
Protein bindingEstradiol: ~98% (to albumin and SHBGTooltip sex hormone-binding globulin)[7][8]
MetabolismCleavage via esterases in the liver, blood, and tissues[4]
MetabolitesEstradiol, valeric acid, and metabolites of estradiol[4]
Elimination half-lifeOral: 12–20 hours (as E2)[4][7]
IM injection: 3.5 (1.2–7.2) days[9]
Duration of actionIM injection:
• 5 mg: 7–8 days[10]
• 10 mg: 10–14 days[11][12]
• 40 mg: 2–3 weeks[11]
• 100 mg: 3–4 weeks[11]
ExcretionUrine (80%)[4]
Identifiers
  • [(8R,9S,13S,14S,17S)-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] pentanoate
JSmol)
Melting point144 to 145 °C (291 to 293 °F)
  • CCCCC(=O)O[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=C3C=CC(=C4)O)C
  • InChI=1S/C23H32O3/c1-3-4-5-22(25)26-21-11-10-20-19-8-6-15-14-16(24)7-9-17(15)18(19)12-13-23(20,21)2/h7,9,14,18-21,24H,3-6,8,10-13H2,1-2H3/t18-,19-,20+,21+,23+/m1/s1
  • Key:RSEPBGGWRJCQGY-RBRWEJTLSA-N

Estradiol valerate (EV), sold for use

fat once every 1 to 4 weeks.[13][14]

Progynova (estradiol valerate) 1 mg oral tablets in the Chinese mainland

fluid retention.[15][13][14] Estradiol valerate is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol.[5][4][16] It is an estrogen ester and a prodrug of estradiol in the body.[16][5][4] Because of this, it is considered to be a natural and bioidentical form of estrogen.[16][17][4][18]

Estradiol valerate was first described in 1940 and was introduced for medical use in 1954.[19][20][21] Along with estradiol cypionate, it is one of the most widely used esters of estradiol.[22] Estradiol valerate is used in the United States, Canada, Europe, and throughout much of the rest of the world.[23][24] It is available as a generic medication.[25]

Medical uses

See also: Estradiol (medication) § Medical uses

The

sex drive in sex offenders.[35]

In the

sleep disturbances, depressive moods, irritability, headaches, and dizziness.[14]

Estradiol valerate by intramuscular injection is usually used at a dosage of 10 to 20 mg every 4 weeks in the treatment of menopausal symptoms and hypoestrogenism due to hypogonadism, castration, or primary ovarian failure in women.

dysfunctional uterine bleeding.[37]: 318 [38]
: 60 

Estrogen dosages for menopausal hormone therapy
Route/form Estrogen Low Standard High
Oral Estradiol 0.5–1 mg/day 1–2 mg/day 2–4 mg/day
Estradiol valerate 0.5–1 mg/day 1–2 mg/day 2–4 mg/day
Estradiol acetate 0.45–0.9 mg/day 0.9–1.8 mg/day 1.8–3.6 mg/day
Conjugated estrogens 0.3–0.45 mg/day 0.625 mg/day 0.9–1.25 mg/day
Esterified estrogens 0.3–0.45 mg/day 0.625 mg/day 0.9–1.25 mg/day
Estropipate 0.75 mg/day 1.5 mg/day 3 mg/day
Estriol 1–2 mg/day 2–4 mg/day 4–8 mg/day
Ethinylestradiola 2.5–10 μg/day 5–20 μg/day –
Nasal spray Estradiol 150 μg/day 300 μg/day 600 μg/day
Transdermal patch Estradiol 25 μg/dayb 50 μg/dayb 100 μg/dayb
Transdermal gel
 Estradiol 0.5 mg/day 1–1.5 mg/day 2–3 mg/day
Vaginal
 Estradiol 25 μg/day – –
Estriol 30 μg/day 0.5 mg 2x/week 0.5 mg/day
SC injection
 Estradiol valerate – – 4 mg 1x/4 weeks
Estradiol cypionate 1 mg 1x/3–4 weeks 3 mg 1x/3–4 weeks 5 mg 1x/3–4 weeks
Estradiol benzoate 0.5 mg 1x/week 1 mg 1x/week 1.5 mg 1x/week
SC implant Estradiol 25 mg 1x/6 months 50 mg 1x/6 months 100 mg 1x/6 months
Footnotes: a = No longer used or recommended, due to health concerns. b = As a single patch applied once or twice per week (worn for 3–4 days or 7 days), depending on the formulation. Note: Dosages are not necessarily equivalent. Sources: See template.

Available forms

See also: Estradiol valerate/norethisterone enantate, Estradiol valerate/hydroxyprogesterone caproate, and Estradiol valerate/prasterone enanthate

Estradiol valerate is and has been available in the form of

oil solution for intramuscular injection in concentrations of 4, 5, 10, 20, and 40 mg/mL and in the form of oral tablets at doses of 0.5, 1, 2, and 4 mg per tablet.[39][19][40][41] In the United States, it is specifically available in formulations of 10, 20, and 40 mg/mL in oil solution (as Delestrogen, as well as generics).[39] Aside from estradiol valerate, the only other injectable estrogen formulations that remain available in the United States are estradiol cypionate (5 mg/mL in oil solution) and conjugated estrogens (25 mg/vial in solution).[39] Some or all oral estradiol valerate tablets are micronized, similarly to oral estradiol tablets.[42]

In addition to single-drug formulations, oral estradiol valerate is available in combination with the

testosterone enantate for use in menopausal hormone therapy, but the latter formulation has been discontinued.[43][39] The availability of estradiol valerate-containing products varies throughout the world.[1]

Available forms of estradiol[a]
Route Ingredient Form Dose[b] Brand names[c]
Oral Estradiol Tablet 0.1, 0.2, 0.5, 1, 2, 4 mg Estrace, Ovocyclin
Estradiol valerate Tablet 0.5, 1, 2, 4 mg Progynova
Transdermal
 Estradiol Patch 14, 25, 37.5, 50, 60, 75, 100 µg/d Climara, Vivelle
Gel pump 0.06% (0.52, 0.75 mg/pump) Elestrin, EstroGel
Gel packet 0.1% (0.25, 0.5, 1.0 mg/pk.) DiviGel, Sandrena
Emulsion 0.25% (25 µg/pouch) Estrasorb
Spray 1.53 mg/spray Evamist, Lenzetto
Vaginal
 Estradiol Tablet 10, 25 µg Vagifem
Cream 0.01% (0.1 mg/gram) Estrace
Insert 4, 10 µg Imvexxy
Ring 2 mg/ring (7.5 µg/d, 3 mon.) Estring
Estradiol acetate Ring 50, 100 µg/d, 3 months Femring
Injection[d] Estradiol Microspheres 1 mg/mL Juvenum E
Estradiol benzoate Oil solution 0.167, 0.2, 0.333, 1, 1.67, 2, 5, 10, 20, 25 mg/mL Progynon-B
Estradiol cypionate Oil solution 1, 3, 5 mg/mL Depo-Estradiol
Estradiol valerate Oil solution 5, 10, 20, 40 mg/mL Progynon Depot
Implant
 Estradiol Pellet 20, 25, 50, 100 mg, 6 mon. Estradiol Implants
Notes and sources:
  1. compounded drugs
    —only commercially produced products. Availability of each product varies by country.
  2. ^ Doses are given per unit (ex: per tablet, per mL).
  3. ^ Other brand names may be manufactured or previously manufactured.
  4. ^ By intramuscular or subcutaneous injection.
Sources: [44][45][46][47][48][49][50][51][52][53][54][55][56][57]

Contraindications

See also: Estradiol (medication) § Contraindications

Contraindications of estrogens include coagulation problems, cardiovascular diseases, liver disease, and certain hormone-sensitive cancers such as breast cancer and endometrial cancer, among others.[58][59][60][61]

Side effects

See also: Estradiol (medication) § Side effects

The

High-dose estrogen therapy with estradiol valerate injections may also cause an increased risk of thromboembolism, changes in blood lipid profile, increased insulin resistance, and increased levels of prolactin.[62]

Overdose

See also: Estradiol (medication) § Overdose

Estradiol valerate has been used at very high doses of 40 to 100 mg once per week in women and men, without overt signs of acute

leg cramps.[58] These side effects can be diminished by reducing the estrogen dosage.[58]

Interactions

See also: Estradiol (medication) § Interactions

Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels.[74]

Pharmacology

Estradiol, the active form of estradiol valerate.

Pharmacodynamics

See also: Pharmacodynamics of estradiol

Estradiol valerate is an

molecular weight of estradiol valerate is about 131% of that of estradiol due to the presence of its C17β valerate ester, and hence estradiol valerate contains about 76% of the amount of estradiol of an equal dose of estradiol.[23][24] Aside from dose adjustment to account for the difference in molecular weight, oral estradiol valerate is considered to be equivalent to oral estradiol.[4] Because estradiol valerate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.[16][17][18]

Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors
Estrogen Other names
RBA
Tooltip Relative binding affinity (%)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 =
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.
Potencies of oral estrogens[data sources 1]
Compound Dosage for specific uses (mg usually)[a]
ETD[b] EPD[b] MSD[b] MSD[c] OID[c] TSD[c]
Estradiol (non-micronized) 30 ≥120–300 120 6 - -
Estradiol (micronized) 6–12 60–80 14–42 1–2 >5 >8
Estradiol valerate 6–12 60–80 14–42 1–2 - >8
Estradiol benzoate - 60–140 - - - -
Estriol ≥20 120–150[d] 28–126 1–6 >5 -
Estriol succinate - 140–150[d] 28–126 2–6 - -
Estrone sulfate 12 60 42 2 - -
Conjugated estrogens 5–12 60–80 8.4–25 0.625–1.25 >3.75 7.5
Ethinylestradiol 200 μg 1–2 280 μg 20–40 μg 100 μg 100 μg
Mestranol 300 μg 1.5–3.0 300–600 μg 25–30 μg >80 μg -
Quinestrol 300 μg 2–4 500 μg 25–50 μg - -
Methylestradiol - 2 - - - -
Diethylstilbestrol 2.5 20–30 11 0.5–2.0 >5 3
DES dipropionate - 15–30 - - - -
Dienestrol 5 30–40 42 0.5–4.0 - -
Dienestrol diacetate 3–5 30–60 - - - -
Hexestrol - 70–110 - - - -
Chlorotrianisene - >100 - - >48 -
Methallenestril - 400 - - - -
Sources and footnotes:
  1. ^ [58][75][76][77][78][79] [80][81][82][83] [84][85][86][87][88][89][90][91][92]
  1. ^ Dosages are given in milligrams unless otherwise noted.
  2. ^ a b c Dosed every 2 to 3 weeks
  3. ^ a b c Dosed daily
  4. ^ a b In divided doses, 3x/day; irregular and atypical proliferation.
Relative oral potencies of estrogens
Estrogen
HF
Tooltip Hot flashes		 VETooltip Vaginal epithelium UCaTooltip Urinary calcium FSHTooltip Follicle-stimulating hormone LHTooltip Luteinizing hormone HDLTooltip High-density lipoprotein-CTooltip Cholesterol SHBGTooltip Sex hormone-binding globulin
CBG
Tooltip Corticosteroid-binding globulin
AGT
Tooltip Angiotensinogen		 Liver
Estradiol 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0
Estrone ? ? ? 0.3 0.3 ? ? ? ? ?
Estriol 0.3 0.3 0.1 0.3 0.3 0.2 ? ? ? 0.67
Estrone sulfate ? 0.9 0.9 0.8–0.9 0.9 0.5 0.9 0.5–0.7 1.4–1.5 0.56–1.7
Conjugated estrogens 1.2 1.5 2.0 1.1–1.3 1.0 1.5 3.0–3.2 1.3–1.5 5.0 1.3–4.5
Equilin sulfate
 ? ? 1.0 ? ? 6.0 7.5 6.0 7.5 ?
Ethinylestradiol 120 150 400 60–150 100 400 500–600 500–600 350 2.9–5.0
Diethylstilbestrol ? ? ? 2.9–3.4 ? ? 26–28 25–37 20 5.7–7.5
Sources and footnotes
Notes: Values are ratios, with estradiol as standard (i.e., 1.0). Abbreviations: HF = Clinical relief of
liver proteins. Liver = Ratio of liver estrogenic effects to general/systemic estrogenic effects (hot flashes/gonadotropins
). 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
ovulation-inhibiting dose of estradiol undecylate
is 20–30 mg/month. Sources: See template.

Effects on liver protein synthesis

The influence of 2 mg/day oral estradiol valerate on

HDL cholesterol and triglycerides.[97][98][99] The influence of 20 or 50 μg/day oral ethinylestradiol on coagulation factors and HDL cholesterol is markedly greater than that of 2 mg/day oral estradiol valerate.[97][100]

combined birth control pills containing ethinylestradiol and a progestin with minimal androgenic or antiandrogenic activity have been found to increase SHBG levels by about 3- to 4-fold.[105]

Pharmacokinetics

See also: Pharmacokinetics of estradiol

Regardless of the

intravenous injection of estradiol valerate, and this indicates very rapid cleavage of the medication upon entering circulation.[4]

Oral administration

hepatic protein synthesis (e.g., of SHBGTooltip sex hormone-binding globulin), again after differences in molecular weight between the two compounds are considered.[4]

A dosage of 1 mg/day oral estradiol valerate has been found to produce approximate circulating concentrations of 50 pg/mL estradiol and 160 pg/mL estrone, while a dosage of 2 mg/day results in circulating levels of 60 pg/mL estradiol and 300 pg/mL estrone.[108] These concentrations of estradiol and estrone are comparable to those observed with 1 and 2 mg/day oral estradiol.[108] A review of selected studies reported a range of mean peak estradiol levels of 24 to 140 pg/mL occurring 1 to 12 hours after administration of 2 mg oral estradiol valerate.[4] A study found that, in accordance with their differences in molecular weights, oral estradiol produced higher levels of estradiol than oral estradiol valerate.[109] Likewise, other studies found that levels of estradiol and estrone are very similar after oral administration of roughly equimolar doses of estradiol (1.5 mg) and estradiol valerate (2 mg).[110][111][112] A study of high-dose oral estradiol valerate found levels of estradiol of about 250 pg/mL after a single 10-mg dose in three women.[107]

Hormone levels with oral estradiol valerate
  • Baseline-adjusted estradiol levels after a single oral dose of 1.5 mg micronized estradiol or 2.0 mg estradiol valerate in postmenopausal women.[113][112] Source was Timmer & Geurts (1999).[112]
    Baseline-adjusted estradiol levels after a single oral dose of 1.5 mg micronized estradiol or 2.0 mg estradiol valerate in postmenopausal women.[113][112] Source was Timmer & Geurts (1999).[112]
  • Estradiol levels after a single oral dose of 2 mg micronized estradiol or 2 mg estradiol valerate and with continuous oral administration of 2 mg/day micronized estradiol or 2 mg/day estradiol valerate (at steady state) in postmenopausal women.[109] Source was Wiegratz et al. (2001).[109]
    Estradiol levels after a single oral dose of 2 mg micronized estradiol or 2 mg estradiol valerate and with continuous oral administration of 2 mg/day micronized estradiol or 2 mg/day estradiol valerate (at steady state) in postmenopausal women.[109] Source was Wiegratz et al. (2001).[109]

Sublingual administration

Hormone levels with 2-mg oral micronized estradiol valerate tablets (Progynova, Schering) taken continuously 3 or 4 times per day by the sublingual route in premenopausal women.[114][115]

Estradiol valerate has been studied by

first pass that occurs with the oral route and results in higher levels of estradiol and improved cycle control.[114][115] Sublingual estradiol valerate is also used in hormone therapy for transgender women.[116]

The administration of 2 mg oral micronized estradiol valerate tablets (Progynova, Schering) sublingually 3 or 4 times per day has been found to result in circulating estradiol levels of about 290 pg/mL to 460 pg/mL in premenopausal women (time of measurements not given).

Steady-state levels of estradiol were achieved within about 2 or 3 days.[114][115] Levels of progesterone, luteinizing hormone, and follicle-stimulating hormone were all considerably suppressed, and ovulation, as well as the associated mid-cycle hormonal surges, were prevented.[114][115] Similarly to oral administration of estradiol, but in contrast to the vaginal and transdermal routes, the ratio of estradiol to estrone is decreased with sublingual administration of either estradiol valerate or estradiol.[114][115][117]

Intramuscular injection

In contrast to oral administration, the bioavailability of estradiol valerate is complete (i.e., 100%) via intramuscular injection.

sample sizes of only 2 or 3 individuals reported an elimination half-life of 4 to 5 days.[4][119][120]

A single intramuscular injection of 4 mg estradiol valerate has been found to result in maximal circulating levels of estradiol of about 390 pg/mL within 3 days of administration, with levels declining to 100 pg/mL (baseline, in the study) by 12 to 13 days.[43] Studies in general have found that a single intramuscular injection of 4 mg estradiol valerate results in peak levels of estradiol of 240 to 540 pg/mL after 1 to 5 days following administration.[120] A study found that a single intramuscular injection of 5 mg estradiol valerate resulted in peak circulating levels of 667 pg/mL estradiol and 324 pg/mL estrone within approximately 2 and 3 days, respectively.[10] The duration of estradiol valerate at this dose and in this study was considered to be 7 to 8 days.[10] Other studies have found that larger doses of intramuscular estradiol valerate exceeding 20 mg have a duration of more than 15 days.[10] A third study, in contrast to the preceding study, found that a single 10 mg intramuscular injection of estradiol valerate resulted in maximal estradiol levels of 506 to 544 pg/mL and maximal estrone levels of 205 to 219 pg/mL in postmenopausal women.[9]

With intramuscular injections of estradiol valerate, it has been reported that a dose of 5 mg has a duration of 7 to 8 days, 10 mg a duration of 10 to 14 days, 40 mg a duration of 2 to 3 weeks (14 to 21 days), and 100 mg a duration of 3 to 4 weeks (21 to 28 days).[11][12][10]

A study of

estrogen deficiency observed estradiol levels of about 3,100 pg/mL at 3 months of therapy and 2,500 pg/mL at 6 months of therapy.[64]

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
chromatographic separation
. Sources: See template.
Hormone levels with estradiol valerate by intramuscular injection
  • Estrogen levels after a single intramuscular injection of 10 mg estradiol valerate in oil in 24 postmenopausal women.[9] Determinations were made for both Progynon Depot 10 and Estradiol Depot 10, for a total of 48 measurements per point.[9] Assays were performed using GC/MS-NCI/SIM.[9] Source was Schug et al. (2012).[9]
    Estrogen levels after a single intramuscular injection of 10 mg estradiol valerate in oil in 24 postmenopausal women.
    NCI/SIM.[9] Source was Schug et al. (2012).[9]
  • Hormone levels after a single intramuscular injection of 5 mg estradiol valerate in oil in 17 postmenopausal women.[121] Assays were performed using EIA.[121] Estrone levels were likely overestimated, possibly due to cross reactivity of the assay with estrogen conjugates.[9] Source was Göretzlehner et al. (2002).[121]
    Hormone levels after a single intramuscular injection of 5 mg estradiol valerate in oil in 17 postmenopausal women.[121] Assays were performed using EIA.[121] Estrone levels were likely overestimated, possibly due to cross reactivity of the assay with estrogen conjugates.[9] Source was Göretzlehner et al. (2002).[121]
  • Hormone levels after a single intramuscular injection of estradiol valerate/norethisterone enanthate (5 mg/50 mg) (Mesigyna) in healthy young men.[122] Testosterone decreased from ~503 ng/dL to ~30 ng/dL (–94%).[122] Source was Valle Alvarez (2011).[122]
    Hormone levels after a single intramuscular injection of
    estradiol valerate/norethisterone enanthate (5 mg/50 mg) (Mesigyna) in healthy young men.[122] Testosterone decreased from ~503 ng/dL to ~30 ng/dL (–94%).[122] Source was Valle Alvarez (2011).[122]
  • Estradiol levels after single intramuscular injections of 5 mg of different estradiol esters in oil in about 10 premenopausal women each.[10] Assays were performed using RIA with CS.[10] Source was Oriowo et al. (1980).[10]
    Estradiol levels after single intramuscular injections of 5 mg of different estradiol esters in oil in about 10 premenopausal women each.
    CS.[10] Source was Oriowo et al. (1980).[10]
  • Estradiol levels after a single intramuscular injection of 10 mg estradiol valerate or 100 mg estradiol undecylate in oil both in 4 individuals each.[123] Subject characteristics and assay method were not described.[123] Source was Vermeulen (1975).[123]
    Estradiol levels after a single intramuscular injection of 10 mg estradiol valerate or 100 mg estradiol undecylate in oil both in 4 individuals each.[123] Subject characteristics and assay method were not described.[123] Source was Vermeulen (1975).[123]
  • Estradiol and DHEA levels after a single intramuscular injection of Gynodian Depot (4 mg estradiol valerate, 200 mg prasterone enanthate in oil) or Primogyn Depot (10 mg estradiol valerate in oil) in women.[124][119][125] Assays were performed using RIA.[119][125] Sources were Düsterberg & Wendt (1983) and Rauramo et al. (1980).[124][119][125]
    Estradiol and DHEA levels after a single intramuscular injection of Gynodian Depot (4 mg estradiol valerate, 200 mg prasterone enanthate in oil) or Primogyn Depot (10 mg estradiol valerate in oil) in women.[124][119][125] Assays were performed using RIA.[119][125] Sources were Düsterberg & Wendt (1983) and Rauramo et al. (1980).[124][119][125]
  • Estradiol levels after a short intravenous infusion of 20 mg estradiol in aqueous solution or an intramuscular injection of equimolar doses of estradiol esters in oil solution in postmenopausal women.[126][127] Assays were performed using RIA with CS.[126][127] Source was Geppert (1975).[126][127]
    Estradiol levels after a short intravenous infusion of 20 mg estradiol in aqueous solution or an intramuscular injection of equimolar doses of estradiol esters in oil solution in postmenopausal women.
    CS.[126][127] Source was Geppert (1975).[126][127]
  • Estradiol levels after an intramuscular injection of 10 mg estradiol valerate in oil, Climacteron (150 mg testosterone enanthate, 1 mg estradiol benzoate, 7.5 mg estradiol dienanthate in oil), and control group in 20, 11, and 11 ovariectomized women, respectively.[128] Assays were performed using RIA.[128] Source was Sherwin et al. (1987).[128]
    Estradiol levels after an intramuscular injection of 10 mg estradiol valerate in oil,
    estradiol dienanthate in oil), and control group in 20, 11, and 11 ovariectomized women, respectively.[128] Assays were performed using RIA.[128] Source was Sherwin et al. (1987).[128]
  • Simplified curves of estradiol levels after injection of different estradiol esters in women.[129] Source was Garza-Flores (1994).[129]
    Simplified curves of estradiol levels after injection of different estradiol esters in women.[129] Source was Garza-Flores (1994).[129]

Subcutaneous injection

Estradiol esters like estradiol valerate and

subcutaneous injection instead of intramuscular injection.[130][131]

Intravenous injection

The administration of estradiol valerate by intravenous injection has been studied.

elimination half-life.[120]

Chemistry

See also: Estrogen ester and List of estrogen esters § Estradiol esters
Estradiol plus the fatty acid valeric acid (valerate) equals estradiol valerate, a C17β ester of estradiol.[107]

Estradiol valerate is a

synthetic estrane steroid and the C17β valerate (pentanoate) fatty acid ester of estradiol.[23][24] It is also known as estradiol 17β-valerate or as estra-1,3,5(10)-triene-3,17β-diol 17β-pentanoate.[23][24] Other common esters of estradiol in use include estradiol cypionate, estradiol enantate, and estradiol acetate, the former two of which are C17β esters of estradiol similarly to estradiol valerate and the latter of which is the C3 acetate ester of estradiol.[23][24]

The experimental log

octanol/water partition coefficient (log P) of estradiol valerate is 5.6.[132]

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
– – – – 1.00 1.00 4.0
Estradiol acetate
C3
Ethanoic acid
 Straight-chain fatty acid 2 1.15 0.87 4.2
Estradiol benzoate
C3 Benzoic acid Aromatic fatty acid – (~4–5) 1.38 0.72 4.7
Estradiol dipropionate
C3, C17β
Propanoic acid
(×2)		 Straight-chain fatty acid 3 (×2) 1.41 0.71 4.9
Estradiol valerate
C17β
Pentanoic acid
 Straight-chain fatty acid 5 1.31 0.76 5.6–6.3
Estradiol benzoate butyrate
C3, C17β Benzoic acid, butyric acid Mixed fatty acid – (~6, 2) 1.64 0.61 6.3
Estradiol cypionate
C17β
Cyclopentylpropanoic acid
 Cyclic fatty acid – (~6) 1.46 0.69 6.9
Estradiol enanthate
C17β
Heptanoic acid
 Straight-chain fatty acid 7 1.41 0.71 6.7–7.3
Estradiol dienanthate
C3, C17β
Heptanoic acid
(×2)		 Straight-chain fatty acid 7 (×2) 1.82 0.55 8.1–10.4
Estradiol undecylate
C17β
Undecanoic acid
 Straight-chain fatty acid 11 1.62 0.62 9.2–9.8
Estradiol stearate
C17β
Octadecanoic acid
 Straight-chain fatty acid 18 1.98 0.51 12.2–12.4
Estradiol distearate
C3, C17β
Octadecanoic acid
(×2)		 Straight-chain fatty acid 18 (×2) 2.96 0.34 20.2
Estradiol sulfate
C3 Sulfuric acid Water-soluble conjugate – 1.29 0.77 0.3–3.8
Estradiol glucuronide
C17β Glucuronic acid Water-soluble conjugate – 1.65 0.61 2.1–2.7
Estramustine phosphated
C3, C17β Normustine, phosphoric acid Water-soluble conjugate – 1.91 0.52 2.9–5.0
Polyestradiol phosphatee
C3–C17β Phosphoric acid Water-soluble conjugate – 1.23f 0.81f 2.9g
Footnotes: a = Length of
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.

History

Estradiol valerate was

micronized preparations of oral estradiol valerate were first introduced under the brand names Progynova 21 and Progynova 21 mite.[137] Along with estradiol benzoate (1933)[144][145][146] and estradiol cypionate (1952),[147] estradiol valerate is one of the most widely used esters of estradiol.[22]

Society and culture

Generic names

Estradiol valerate is the

INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANMTooltip British Approved Name, and JANTooltip Japanese Accepted Name, while oestradiol valerate was formerly its BANMTooltip British Approved Name.[23][24][148]

Brand names

Estradiol valerate has been marketed under the brand names Altadiol, Androtardyl-Oestradiol, Ardefem, Climaval, Cyclabil, Cyclocur, Deladiol, Delahormone Unimatic, Delestrogen, Delestrogen 4X, Depogen, Diol-20, Dioval, Ditate, Dura-Estate, Dura-Estradiol, Duratrad, Duragen, Estate, Estra-L, Estradiol Depot, Estraval, Estraval Depot, Estraval PA, Estravel, Femogen, Femogex, Gynogen L.A., Gynokadin, Lastrogen, Menaval, Merimono, Neofollin, Nuvelle, Oestrogynal, Ostrin Depo, Pelanin, Pharlon, Postoval, Primogyna, Primogyn, Primogyn Depot, Progynon, Progynon Depot, Progynova, Repestrogen, Repo-Estra, Reposo-E, Retestrin, Ronfase, Span-Est, Testaval, and Valergen, among others.

oil solution of estradiol valerate.[150][151]

Availability

See also: List of estrogens available in the United States

Oral estradiol valerate is used primarily in

combined oral contraceptive (under the brand name Natazia).[39] Estradiol valerate by intramuscular injection is available under the brand name Delestrogen in the United States and Canada and under the brand name Progynon Depot in Europe and elsewhere in the world.[39][24]

Research

SH-834 was a combination of 90 mg estradiol valerate and 300 mg gestonorone caproate for weekly intramuscular injection that was developed by Schering in the 1970s.[68][153][154] It was investigated clinically as a treatment for breast cancer and was found to be effective, but was never marketed.[68][66]

See also

References

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    . Intramuscular: For replacement therapy, (Estradiol, Estradiol Benzoate) 0.5 to 1.5 mg two or three times weekly; (Estradiol Cypionate) 1 to 5 mg weekly for two or three weeks; (Estradiol Dipropionate) 1 to 5 mg every one to two weeks; (Estradiol Valerate) 10 to 40 mg every one to four weeks.
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    . Oestradiol valerate and oestradiol in a micronized form are the most widely used oestrogen per os for steroid substitution therapy. Our regimen, as of most other groups [...] is oestradiol valerate (Progynova; Schering, Berlin, Germany) given in various concentrations throughout the cycle [...]. According to Norfolk's protocol, 2 mg of micronized oestradiol valerate are given on cycle days 1–5. [...] In tablet form, micronized oestradiol valerate is also efficiently absorbed [...]
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    . 300 μg 17β-estradiol (Aerodiol®; Servier, Chambrayles-Tours, France) was administered via the nasal route by a gynecologist. This product is unavailable after March 31, 2007 because its manufacturing and marketing are being discontinued.
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    . Dosierungsbeispiele bei Mammahypoplasie und Infantilismus [...] Parenteral 1. 40 mg Estradiolvalerat (Estradiol-Depot 10 mg JENAPHARM) und 250 mg Hydroxyprogesteroncaproat (Progesteron-Depot JENAPHARM, Proluton Depot) i. m. einmal wöchentlich über 15–20 Wochen lang. 2. 20–40 mg Estradiolvalerat (Estradiol-Depot 10 mg JENAPHARM) i. m. in der ersten und zweiten Woche. 40 mg Estradiolvalerat (Estradiol-Depot 10 mg JENAPHARM) und 250 mg Hydroxyprogesteroncaproat (Progesteron-Depot JENAPHARM, Proluton Depot) i. m. in der dritten und vierten Woche. Therapiedauer 4–5 Monate. Evtl. Abstand zwischen 2 Injektionen auf 2 Wochen erweitern (Abb. 6.2).
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  73. ISSN 0022-4499
    . Estrogen treatment—as already indicated—helps greatly but does not cure. I have employed either Squibb's Delestrogen, a slowly absorbing, highly potent preparation which is, chemically, estradiol valerate (40 mg. to 1 cc); or the still more potent Delestrec, which is estradiol undecylate (100 mg. to 1 cc). This preparation, however, is not yet on the market in this country, though it is widely used in Europe. In the majority of cases, I used from 30 to 100 mg. weekly, or every two to three weeks, by intramuscular injection.
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    . Um die "Menarche" sollte eine verstärkte Substitutionstherapie (20 Tage lang tgl. 0,1 mg Follikelhormon per os oder einmalig Progynon-Depot (10 mg i.m.), [...]
  137. ^
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    . With Progynon Depot-10, an oily solution of 10 mg estradiol valerate, an injection preparation had been available since 1953 and since 1966 coated tablets with estradiol valerate for oral therapy. The first Schering preparation containing micronized estradiol was marketed in 1968 as Progynova 21 (2 mg) and Progynova 21 mite (1 mg).
  138. S2CID 20357182
    . NEUE SPEZIALITATEN [...] Progynova. 1 Dragee enthält 2 mg Oestradiolvalerinat (Klimakterium). Hersteller: Schering AG, Berlin 65.
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    . Progynon-B, Schering Corporation: This is crystalline hydroxyestrin benzoate obtained by hydrogenation of theelin and subsequent conversion to the benzoate. [...] Progynon-B is marketed in ampules containing 1 cc. of a sesame oil solution of hydroxyestrin benzoate of either 2,500, 5,000, 10,000 or 50,000 international units.
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Further reading
Retrieved from "https://en.wikipedia.org/w/index.php?title=Estradiol_valerate&oldid=1214439678"