Estradiol valerate
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Pronunciation | /ˌɛstrəˈdaɪoʊl ˈvæləreɪt/ ES-trə-DY-ohl VAL-ə-rayt[1] |
Trade names | Delestrogen, Progynon Depot, Progynova, many others |
Other names | EV; E2V; Oestradiol valerate; Estradiol pentanoate; Estradiol valerianate |
Routes of administration | By mouth, intramuscular injection,[2] subcutaneous injection |
Drug class | Estrogen; Estrogen ester |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | Oral: 3–5%[4][5] IM: 100%[4] |
Protein binding | Estradiol: ~98% (to albumin and SHBG )[6][7] |
Metabolism | Cleavage via esterases in the liver, blood, and tissues[4] |
Metabolites | Estradiol, valeric acid, and metabolites of estradiol[4] |
Elimination half-life | Oral: 12–20 hours (as E2 )[4][8] IM: 4–5 days[4] |
Duration of action | IM (5 mg): 7–8 days[9] IM (10–30 mg): 1–4 weeks[10] |
Excretion | Urine (80%)[4] |
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ECHA InfoCard | 100.012.327 |
Chemical and physical data | |
Formula | C23H32O3 |
Molar mass | 356.498 g/mol g·mol−1 |
3D model (JSmol) | |
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Estradiol valerate, sold under the brand names Delestrogen, Progynon Depot, and Progynova among others, is an estrogen medication which is used in hormone therapy for menopausal symptoms and low estrogen levels in women, in hormone therapy for transgender women, and in hormonal birth control for women.[5][4][10][11] It is also used in the treatment of prostate cancer in men.[10] The medication is taken by mouth or by injection into muscle once every 1 to 4 weeks.[10][11]
Side effects of estradiol valerate include breast tenderness, breast enlargement, nausea, headache, and fluid retention.[12][10][11] Estradiol valerate is a synthetic estrogen and hence is an agonist of the estrogen receptor (ER), the biological target of estrogens like estradiol.[5][4][13] It is an estrogen ester and a prodrug of estradiol in the body.[13][5][4] Because of this, it is considered to be a natural and bioidentical form of estrogen.[13][4][14]
Estradiol valerate was first described in 1940 and was introduced for medical use in 1954.[15][16][17] Along with estradiol cypionate, it is one of the most widely used esters of estradiol.[18] Estradiol valerate is used in the United States, Canada, Europe, and throughout much of the rest of the world.[19][20] It is available as a generic medication.[21]
Medical uses
The medical uses of estradiol valerate are the same as those of estradiol and other estrogens. Examples of indications for the medication include hormone therapy and hormonal contraception. In regard to the latter, estradiol valerate is available in combination with a progestin as a combined estradiol-containing oral contraceptive (with dienogest)[22] and as a combined injectable contraceptive.[23][24][25] Along with estradiol cypionate, estradiol undecylate, and estradiol benzoate, estradiol valerate is used as a form of high-dose estrogen therapy in feminizing hormone therapy for transgender women.[26][27][28][29] It is also used as a form of high-dose estrogen therapy in the treatment of prostate cancer in men.[10]
In the United States, the approved indications of estradiol valerate injections include the treatment of moderate to severe hot flashes and vaginal atrophy associated with menopause in women, the treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure in women, and the palliative treatment of advanced prostate cancer in men.[10] Elsewhere in the world, oral estradiol valerate is similarly approved for the treatment of symptoms associated with menopause or hypoestrogenism due to castration in women.[11] Such symptoms may include hot flashes, outbreaks of sweat, sleep disturbances, depressive moods, irritability, headaches, and dizziness.[11]
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.[10] It is usually used in the treatment of advanced prostate cancer in men at a dosage of 30 mg or more every 1 to 2 weeks by intramuscular injection.[10] In transgender women, estradiol valerate given by intramuscular injection is usually used at a dosage of 5 to 20 mg, but up to 30 to 40 mg, once every 2 weeks.[27][28][26]
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 | ||||
IM or 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
Estradiol valerate is and has been available in the form of vials and ampoules for intramuscular injection in concentrations of 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.[30][15][31][32] In the United States, it is specifically available in formulations of 10, 20, and 40 mg/mL (as Delestrogen, as well as generics).[30] 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) and conjugated estrogens (25 mg/vial in solution).[30] Some or all oral estradiol valerate tablets are micronized, similarly to oral estradiol tablets.[33]
In addition to single-drug formulations, oral estradiol valerate is available in combination with the progestin dienogest as a combined oral contraceptive and intramuscular estradiol valerate is marketed in combination with the progestins hydroxyprogesterone caproate and norethisterone enantate as combined injectable contraceptives.[30][22][23][24][25][1] Intramuscular estradiol valerate has also been marketed in combination with testosterone enantate, but this formulation has been discontinued.[30] The availability of estradiol valerate-containing products varies throughout the world.[1]
Route | Ingredient | Form | Dose[b] | Brand names[c] |
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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:
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Contraindications
Side effects
The side effects of estradiol valerate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma.[12][45] 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.[45]
Overdose
Interactions
Pharmacology
Pharmacodynamics
Estradiol valerate is an estradiol ester, or a prodrug of estradiol.[13][5] As such, it is an estrogen, or an agonist of the estrogen receptors.[5][13] The affinity of estradiol valerate for the estrogen receptor is approximately 50 times lower than that of estradiol.[4] In addition, estradiol valerate is rapidly cleaved into estradiol and is unable to reach target tissues in concentrations of significance, if at all.[4] As such, estradiol valerate is essentially inactive in terms of estrogenic effect itself, acting solely as a prodrug to estradiol.[4] The 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.[19][20] 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.[13][14]
Compound | Dosage for specific uses (mg usually)[a] | ||||||
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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 | - | - | - | - | |
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. |
Pharmacokinetics
Regardless of the route of administration, estradiol valerate behaves as a prodrug of estradiol via cleavage by esterases into estradiol and the natural fatty acid valeric acid.[5][13][4][5][65] This cleavage occurs not only in the liver, but also in the blood and in tissues, and the hydrolysis of estradiol valerate into estradiol and valeric acid is complete regardless of whether the medication is administered orally or parenterally.[4] High levels of circulating estradiol are found after an intravenous injection of estradiol valerate, and this indicates very rapid cleavage of the medication upon entering circulation.[4] In contrast to estradiol, which can distribute into and exert its effects in target tissues, valeric acid is quickly metabolized via beta oxidation (see also fatty acid metabolism).[4]
Oral administration
![](http://upload.wikimedia.org/wikipedia/commons/thumb/2/2c/Estradiol_levels_after_a_single_dose_and_with_continuous_administration_of_oral_estradiol_or_oral_estradiol_valerate_in_women.png/375px-Estradiol_levels_after_a_single_dose_and_with_continuous_administration_of_oral_estradiol_or_oral_estradiol_valerate_in_women.png)
Esterification of the C17β position of estradiol as in estradiol valerate reduces the metabolism of estradiol valerate by 17β-hydroxysteroid dehydrogenase (17β-HSD).[5] As approximately 80% of estradiol is metabolized into estrone (and estrone sulfate) by 17β-HSD during first-pass metabolism, this improves the metabolic stability and hence bioavailability of estradiol valerate.[13] However, estradiol valerate is hydrolyzed into estradiol and valeric acid in the intestines, and hence, is still subject to extensive first-pass metabolism.[5] As such, the oral bioavailability of estradiol valerate is only around 3 to 5%, and is similar to that of oral estradiol.[4][5][67] All oral tablets in the cases of both estradiol and estradiol valerate seem to be micronized.[33] Due to its nature as a rapidly converted prodrug of estradiol, the pharmacokinetics of oral estradiol valerate are similar to those of oral estradiol.[4][5] Moreover, the pharmacodynamics and potency (after differences in molecular weight are taken into account) of oral estradiol valerate are considered to be equivalent to those of oral estradiol.[4] This is also notably true for effects on hepatic protein synthesis (e.g., of SHBG ), 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.[68] These concentrations of estradiol and estrone are comparable to those observed with 1 and 2 mg/day oral estradiol.[68] 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.[66] Likewise, another study found that levels of estradiol and estrone were very similar after oral administration of roughly equimolar doses of estradiol (1.5 mg) and estradiol valerate (2 mg).[69] 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.[67]
Sublingual administration
![](http://upload.wikimedia.org/wikipedia/commons/thumb/0/0c/Hormone_levels_with_oral_estradiol_valerate_tablets_%28Progynova%29_taken_sublingually_in_premenopausal_women.png/375px-Hormone_levels_with_oral_estradiol_valerate_tablets_%28Progynova%29_taken_sublingually_in_premenopausal_women.png)
Estradiol valerate has been studied by sublingual administration in premenopausal women for the purpose of cycle control and ovulation suppression in egg donation and surrogacy.[70][71] It has been investigated for this indication, along with vaginal and transdermal estradiol, because oral estradiol valerate is sometimes unable to achieve adequate estradiol levels and hence proper cycle control in this situation.[70][71] Sublingual administration of estradiol valerate bypasses the first pass that occurs with the oral route and results in higher levels of estradiol and improved cycle control.[70][71] The administration of 2 mg oral micronized estradiol valerate tablets (Progynova, Schering) sublingually 3 or 4 times per day resulted in circulating estradiol levels of about 290 pg/mL to 460 pg/mL in premenopausal women (time of measurements not given).[70][71] Steady-state levels of estradiol were achieved within about 2 or 3 days.[70][71] 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.[70][71] 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 both estradiol valerate and estradiol.[70][71][72]
Intramuscular injection
In contrast to oral administration, the bioavailability of estradiol valerate is complete (i.e., 100%) via intramuscular injection.[4][5] Due to the far greater bioavailability of intramuscular estradiol valerate relative to oral, the former is substantially stronger (in terms of potency) than the latter.[4] As an example, a single 4 mg intramuscular injection is said to be approximately equivalent to 2 mg/day of the medication administered orally over the course of 3 weeks.[4] Estradiol valerate, when given intramuscularly in oil, has a relatively long duration due to the formation of an intramuscular depot from which the medication is slowly released and absorbed.[4][73] Upon intramuscular injection of estradiol valerate in an oil solution, the solvent (i.e., oil) is absorbed, and a primary microcrystalline depot is formed within the muscle at the site of injection.[5] In addition, a secondary depot may also be formed in adipose tissue.[5] The slow release of estradiol valerate is caused by the increased lipophilicity of the medication, which in turn is due to its long fatty acid valeric acid ester moiety.[4] The elimination half-life of intramuscularly administered estradiol valerate in oil is reported to be 4 to 5 days.[4]
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.[74] 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.[75] 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.[9] The duration of estradiol valerate at this dose and in this study was considered to be 7 to 8 days.[9] Other studies have found that larger doses of intramuscular estradiol valerate exceeding 20 mg have a duration of more than 15 days.[9] 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.[76]
A study of high-dose combined intramuscular administration of 40 mg estradiol valerate and 250 mg hydroxyprogesterone caproate per week for 6 months (described as a "pseudopregnancy" regimen) in hypogonadal women found that circulating levels of estradiol increased from 27.8–34.8 pg/mL to 3028–3226 pg/mL after three months and to 2491–2552 pg/mL after 6 months of treatment.[77]
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. |
Template:Hormone levels with intramuscular estradiol valerate
Subcutaneous injection
Estradiol esters like estradiol valerate and estradiol cypionate can be given by subcutaneous injection instead of intramuscular injection.[78][79]
Intravenous injection
The administration of estradiol valerate by intravenous injection has been studied.[4][75] It has been found to be very rapidly cleaved into estradiol.[4][75] The bioavailability and metabolism of estradiol valerate does not differ with intravenous versus intramuscular injection.[75]
Chemistry
![](http://upload.wikimedia.org/wikipedia/commons/thumb/9/95/Estradiol_esterification_into_estradiol_valerate.png/325px-Estradiol_esterification_into_estradiol_valerate.png)
Estradiol valerate is a synthetic estrane steroid and the C17β valerate (pentanoate) fatty acid ester of estradiol.[19][20] It is also known as estradiol 17β-valerate or as estra-1,3,5(10)-triene-3,17β-diol 17β-pentanoate.[19][20] 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.[19][20]
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 ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic or cyclic 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. |
History
Estradiol valerate was patented by Ciba in 1940 and 1941, with a priority date of 1936.[15][80] It was synthesized and studied, along with a variety of other estradiol esters, by Karl Junkmann of Schering AG in 1953.[81][82] The medication first introduced for medical use by Squibb in 1954 under the brand name Delestrogen in the United States.[16][17] Subsequently, estradiol valerate was marketed widely in Europe as Progynon Depot and Progynova.[20][16] Along with estradiol benzoate (1936)[83][84] and estradiol cypionate (1952),[85] estradiol valerate has become one of the most widely used esters of estradiol.[18]
Society and culture
Generic names
Estradiol valerate is the generic name of the drug and its INN , USAN , BANM , and JAN , while oestradiol valerate was formerly its BANM .[19][20][86]
Brand names
Estradiol valerate is or has been marketed under the brand names Altadiol, Deladiol, Delestrogen, Estraval, Estraval Depot, Neofollin, Progynon Depot, Progynova, and Valergen, among many others.[19][20][86]
Availability
Oral estradiol valerate is used primarily in Europe, under the brand name Progynova.[87] Although oral estradiol valerate was previously available in the United States,[20] it is no longer available in this country except in combination with dienogest as a combined oral contraceptive (under the brand name Natazia).[30] 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.[30][20]
See also
References
- ^ a b c d https://www.drugs.com/cons/estradiol-and-dienogest.html Cite error: The named reference "Drugs.com" was defined multiple times with different content (see the help page).
- ^ Christoph Zink (1 January 1988). Dictionary of Obstetrics and Gynecology. Walter de Gruyter. p. 86. ISBN 978-3-11-085727-6. Retrieved 20 May 2012.
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af Düsterberg B, Nishino Y (December 1982). "Pharmacokinetic and pharmacological features of oestradiol valerate". Maturitas. 4 (4): 315–24. doi:10.1016/0378-5122(82)90064-0. PMID 7169965.
- ^ a b c d e f g h i j k l m n o 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.
- ^ Stanczyk, Frank Z.; Archer, David F.; Bhavnani, Bhagu R. (2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment". Contraception. 87 (6): 706–727. doi:10.1016/j.contraception.2012.12.011. ISSN 0010-7824. PMID 23375353.
- ^ Tommaso Falcone; William W. Hurd (2007). Clinical Reproductive Medicine and Surgery. Elsevier Health Sciences. pp. 22, 362, 388. ISBN 0-323-03309-1.
- ^ Stanczyk, Frank Z.; Archer, David F.; Bhavnani, Bhagu R. (2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment". Contraception. 87 (6): 706–727. doi:10.1016/j.contraception.2012.12.011. ISSN 0010-7824. PMID 23375353.
- ^ a b c d Oriowo MA, Landgren BM, Stenström B, Diczfalusy E (April 1980). "A comparison of the pharmacokinetic properties of three estradiol esters". Contraception. 21 (4): 415–24. doi:10.1016/S0010-7824(80)80018-7. PMID 7389356.
- ^ a b c d e f g h i https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009402s052lbl.pdf
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- ^ a b Amit K. Ghosh (23 September 2010). Mayo Clinic Internal Medicine Board Review. OUP USA. pp. 222–. ISBN 978-0-19-975569-1.
- ^ a b c d e f g h Michael Oettel; Ekkehard Schillinger (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. p. 261. ISBN 978-3-642-60107-1.
Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens.
- ^ a b Nagrath Arun; Malhotra Narendra; Seth Shikha (15 December 2012). Progress in Obstetrics and Gynecology--3. Jaypee Brothers Medical Publishers Pvt. Ltd. pp. 419–. ISBN 978-93-5090-575-3.
- ^ a b c d A. Kleemann; J. Engel; B. Kutscher; D. Reichert (14 May 2014). Pharmaceutical Substances, 5th Edition, 2009: Syntheses, Patents and Applications of the most relevant APIs. Thieme. pp. 1167–1174. ISBN 978-3-13-179525-0. Cite error: The named reference "KleemannEngel2014" was defined multiple times with different content (see the help page).
- ^ a b c William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1477–. ISBN 978-0-8155-1856-3.
- ^ a b Larry L. Duetsch (1969). Research and development, market power, and patent policy in ethical drugs. University of Wisconsin--Madison. p. 95.
- ^ a b Samuel S. C. Yen (1991). Reproductive endocrinology: physiology, pathophysiology, and clinical management. Saunders. ISBN 978-0-7216-3206-3. Retrieved 20 May 2012.
- ^ a b c d e f g J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 898–. ISBN 978-1-4757-2085-3.
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- ^ https://www.drugs.com/availability/generic-delestrogen.html
- ^ a b Guida M, Bifulco G, Di Spiezio Sardo A, Scala M, Fernandez LM, Nappi C (2010). "Review of the safety, efficacy and patient acceptability of the combined dienogest/estradiol valerate contraceptive pill". International Journal of Women's Health. 2: 279–90. doi:10.2147/IJWH.S6954. PMC 2990895. PMID 21151673.
{{cite journal}}
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- ^ a b http://www.wjpps.com/download/article/1412071798.pdf
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- ^ a b Wesp LM, Deutsch MB (March 2017). "Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons". Psychiatr. Clin. North Am. 40 (1): 99–111. doi:10.1016/j.psc.2016.10.006. PMID 28159148.
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- ^ Gianna E. Israel; Donald E. Tarver; Joy Diane Shaffer (1 March 2001). Transgender Care: Recommended Guidelines, Practical Information, and Personal Accounts. Temple University Press. pp. 64–. ISBN 978-1-56639-852-7.
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- ^ Kenneth L. Becker (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 2153–. ISBN 978-0-7817-1750-2.
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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 [...]
- ^ "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 26 July 2018.
- ^ Lobo RA (5 June 2007). Treatment of the Postmenopausal Woman: Basic and Clinical Aspects. Academic Press. pp. 177, 217–226, 770–771. ISBN 978-0-08-055309-2.
- ^ Falcone T, Hurd WW (14 June 2017). Clinical Reproductive Medicine and Surgery: A Practical Guide. Springer. pp. 179–. ISBN 978-3-319-52210-4.
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- ^ "AERODIOL (Oestradiol hemihydrate 150 micrograms/actuation)" (PDF). Servier Laboratories (Aust) Pty Ltd.
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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.
- ^ Plouffe Jr L, Ravnikar VA, Speroff L, Watts NB (6 December 2012). Comprehensive Management of Menopause. Springer Science & Business Media. pp. 271–. ISBN 978-1-4612-4330-4.
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- ^ Lauritzen C (June 1977). "[Estrogen thearpy in practice. 3. Estrogen preparations and combination preparations]" [Estrogen therapy in practice. 3. Estrogen preparations and combination preparations]. Fortschritte Der Medizin (in German). 95 (21): 1388–92. PMID 559617.
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- ^ Pschyrembel W (1968). Praktische Gynäkologie: für Studierende und Ärzte. Walter de Gruyter. pp. 598–599. ISBN 978-3-11-150424-7.
- ^ Lauritzen CH (January 1976). "The female climacteric syndrome: significance, problems, treatment". Acta Obstetricia Et Gynecologica Scandinavica. Supplement. 51: 47–61. doi:10.3109/00016347509156433. PMID 779393.
- ^ Lauritzen C (1975). "The Female Climacteric Syndrome: Significance, Problems, Treatment". Acta Obstetricia et Gynecologica Scandinavica. 54 (s51): 48–61. doi:10.3109/00016347509156433. ISSN 0001-6349.
- ^ Kopera H (1991). "Hormone der Gonaden". Hormonelle Therapie für die Frau. Kliniktaschenbücher. pp. 59–124. doi:10.1007/978-3-642-95670-6_6. ISBN 978-3-540-54554-5. ISSN 0172-777X.
- ^ Scott WW, Menon M, Walsh PC (April 1980). "Hormonal Therapy of Prostatic Cancer". Cancer. 45 (Suppl 7): 1929–1936. doi:10.1002/cncr.1980.45.s7.1929. PMID 29603164.
- ^ Leinung MC, Feustel PJ, Joseph J (2018). "Hormonal Treatment of Transgender Women with Oral Estradiol". Transgender Health. 3 (1): 74–81. doi:10.1089/trgh.2017.0035. PMC 5944393. PMID 29756046.
- ^ Ryden AB (1950). "Natural and synthetic oestrogenic substances; their relative effectiveness when administered orally". Acta Endocrinologica. 4 (2): 121–39. doi:10.1530/acta.0.0040121. PMID 15432047.
- ^ Ryden AB (1951). "The effectiveness of natural and synthetic oestrogenic substances in women". Acta Endocrinologica. 8 (2): 175–91. doi:10.1530/acta.0.0080175. PMID 14902290.
- ^ Kottmeier HL (1947). "Ueber blutungen in der menopause: Speziell der klinischen bedeutung eines endometriums mit zeichen hormonaler beeinflussung: Part I". Acta Obstetricia et Gynecologica Scandinavica. 27 (s6): 1–121. doi:10.3109/00016344709154486. ISSN 0001-6349.
There is no doubt that the conversion of the endometrium with injections of both synthetic and native estrogenic hormone preparations succeeds, but the opinion whether native, orally administered preparations can produce a proliferation mucosa changes with different authors. PEDERSEN-BJERGAARD (1939) was able to show that 90% of the folliculin taken up in the blood of the vena portae is inactivated in the liver. Neither KAUFMANN (1933, 1935), RAUSCHER (1939, 1942) nor HERRNBERGER (1941) succeeded in bringing a castration endometrium into proliferation using large doses of orally administered preparations of estrone or estradiol. Other results are reported by NEUSTAEDTER (1939), LAUTERWEIN (1940) and FERIN (1941); they succeeded in converting an atrophic castration endometrium into an unambiguous proliferation mucosa with 120–300 oestradiol or with 380 oestrone.
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{{cite journal}}
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Further reading
- Vermeulen A (1975). "Longacting steroid preparations". Acta Clin Belg. 30 (1): 48–55. doi:10.1080/17843286.1975.11716973. PMID 1231448.
- Düsterberg B, Nishino Y (1982). "Pharmacokinetic and pharmacological features of oestradiol valerate". Maturitas. 4 (4): 315–24. doi:10.1016/0378-5122(82)90064-0. PMID 7169965.
- Sang GW (1994). "Pharmacodynamic effects of once-a-month combined injectable contraceptives". Contraception. 49 (4): 361–85. doi:10.1016/0010-7824(94)90033-7. PMID 8013220.
- O'Connell MB (1995). "Pharmacokinetic and pharmacologic variation between different estrogen products". J Clin Pharmacol. 35 (9 Suppl): 18S–24S. doi:10.1002/j.1552-4604.1995.tb04143.x. PMID 8530713.
- 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.
- Stanczyk, Frank Z.; Archer, David F.; Bhavnani, Bhagu R. (2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment". Contraception. 87 (6): 706–727. doi:10.1016/j.contraception.2012.12.011. ISSN 0010-7824. PMID 23375353.