Estriol succinate

Last updated
Estriol succinate
Estriol disuccinate.svg
Estriol succinate molecule ball.png
Clinical data
Trade names Synapause, others
Other namesOestriol succinate; Estriol disuccinate; Estriol hemisuccinate; Succinylestriol; Estriol 16α,17β-di(hydrogen succinate)
Routes of
administration
By mouth, vaginal [1]
Drug class Estrogen; Estrogen ester
Identifiers
  • 4-{[(8R,9S,13S,14S,16R,17R)-17-(3-carboxypropanoyloxy)-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-16-yl]oxy}-4-oxobutanoic acid
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard 100.007.442 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C26H32O9
Molar mass 488.533 g·mol−1
3D model (JSmol)
  • C[C@]12CC[C@H]3[C@@H](CCc4cc(O)ccc34)[C@@H]1C[C@@H](OC(=O)CCC(O)=O)[C@@H]2OC(=O)CCC(O)=O
  • InChI=1S/C26H32O9/c1-26-11-10-17-16-5-3-15(27)12-14(16)2-4-18(17)19(26)13-20(34-23(32)8-6-21(28)29)25(26)35-24(33)9-7-22(30)31/h3,5,12,17-20,25,27H,2,4,6-11,13H2,1H3,(H,28,29)(H,30,31)/t17-,18-,19+,20-,25+,26+/m1/s1
  • Key:VBRVDDFOBZNCPF-BRSFZVHSSA-N

Estriol succinate, sold under the brand name Synapause among others, is an estrogen medication which is used in the treatment of menopausal symptoms. [1] It is taken by mouth, in through the vagina, and by injection. [1] [2] [3]

Contents

Medical uses

Estriol succinate is used in menopausal hormone therapy in the treatment and prevention of menopausal symptoms such as hot flashes, vaginal atrophy, and osteoporosis. [1] Unlike other estrogens, depending on how it is used (i.e., how often it is taken and at what dosage), estriol succinate may not require concomitant therapy with a progestogen to prevent endometrial hyperplasia and endometrial cancer in women with intact uteruses. [1]

The clinical effects of estriol succinate in the treatment of menopausal symptoms have been characterized in a large 5-year clinical trial of 911 menopausal women. [4] [5] [6]

Available forms

Estriol succinate is and has been available in the form of 2 and 4 mg oral tablets, as a 0.1% vaginal cream, and as a 20 mg vial for use by injection. [2] [3]

Side effects

Pharmacology

Estriol succinate is an estrogen ester, specifically, an ester of estriol, and acts as a prodrug of estriol in the body. [7] [1] It is described as a weak estrogen in comparison to estradiol valerate. [1] [8] Estriol succinate is used medically via oral and vaginal routes similarly. [1] In estriol succinate, two of the hydroxyl groups of estriol, those at the C16α and C17β positions, are esterified with succinic acid. [1] As such, when adjusted for differences in molecular weight, a dose of 2 mg estriol succinate is equivalent to 1.18 mg unconjugated estriol. [1] Unlike other estrogen esters, such as estradiol valerate, estriol succinate is hydrolyzed almost not at all in the intestinal mucosa when taken orally, and in relation to this, is absorbed more slowly than is estriol. [1] Consequently, oral estriol succinate is a longer-acting form of estriol than oral estriol. [9] Instead of in the gastrointestinal tract, oral estriol succinate is cleaved into estriol mainly in the liver. [1] After a single 8 mg oral dose of estriol succinate, maximum levels of circulating estriol of 40 pg/mL are attained within 12 hours, and this increases up to 80 pg/mL with continued daily administration. [1]

Potencies of oral estrogens [data sources 1]
CompoundDosage for specific uses (mg usually) [lower-alpha 1]
ETD [lower-alpha 2] EPD [lower-alpha 2] MSD [lower-alpha 2] MSD [lower-alpha 3] OID [lower-alpha 3] TSD [lower-alpha 3]
Estradiol (non-micronized) 30≥120–3001206--
Estradiol (micronized) 6–1260–8014–421–2>5>8
Estradiol valerate 6–1260–8014–421–2->8
Estradiol benzoate -60–140----
Estriol ≥20120–150 [lower-alpha 4] 28–1261–6>5-
Estriol succinate-140–150 [lower-alpha 4] 28–1262–6--
Estrone sulfate 1260422--
Conjugated estrogens 5–1260–808.4–250.625–1.25>3.757.5
Ethinylestradiol 200 μg1–2280 μg20–40 μg100 μg100 μg
Mestranol 300 μg1.5–3.0300–600 μg25–30 μg>80 μg-
Quinestrol 300 μg2–4500 μg25–50 μg--
Methylestradiol -2----
Diethylstilbestrol 2.520–30110.5–2.0>53
DES dipropionate -15–30----
Dienestrol 530–40420.5–4.0--
Dienestrol diacetate 3–530–60----
Hexestrol -70–110----
Chlorotrianisene ->100-->48-
Methallenestril -400----
Sources and footnotes:
  1. Dosages are given in milligrams unless otherwise noted.
  2. 1 2 3 Dosed every 2 to 3 weeks
  3. 1 2 3 Dosed daily
  4. 1 2 In divided doses, 3x/day; irregular and atypical proliferation.

Chemistry

Estriol succinate, also known as estriol disuccinate or as estriol 16α,17β-di(hydrogen succinate), is a synthetic estrane steroid and a derivative of estriol. [7] [29] [30] It is specifically the C16α and C17β disuccinate ester of estriol. [7] [29] [30] [1] The medication is provided both as estriol succinate and as estriol sodium succinate, the sodium salt. [7] [29] Other marketed estriol esters besides estriol succinate include estriol acetate benzoate and estriol tripropionate, whereas estriol dihexanoate, estriol dipropionate, and estriol triacetate are estriol esters that were never marketed. [7] [29] Quinestradol is an estriol ether and has also been marketed. [7] [29] Polyestriol phosphate is an ester of estriol in the form of a polymer, and was previously marketed. [31] [32] [33] [34]

History

Estriol succinate was introduced for medical use in 1966. [35]

Society and culture

Generic names

Estriol succinate is the generic name of the drug and its INN Tooltip International Nonproprietary Name and BAN Tooltip British Approved Name. [7] [29] [36] [30] [35] Other synonyms include oestriol succinate, estriol disuccinate, and estriol hemisuccinate. [7] [29] [36] [30] When provided as the sodium salt, estriol succinate is known as estriol sodium succinate (BAN Tooltip British Approved Name) or as oestriol sodium succinate. [7] [29]

Brand names

Estriol succinate has been marketed under brand names including Blissel, Evalon, Gelistrol, Hemostyptanon, Orgastyptin, Ovestin, Sinapause, Styptanon, Synapsa, Synapasa, Synapausa, and Synapause, among others. [7] [29] [36] [30] Estriol sodium succinate has been marketed specifically under the brand names Pausan and Styptanon. [7] [29]

Availability

Estriol succinate is or has been marketed in Europe, Hong Kong, and Mexico. [29] [30]

Research

Estriol succinate was under development for the treatment of multiple sclerosis in the United States and worldwide, and reached phase II clinical trials for this indication, but development was discontinued due to insufficient effectiveness. [37] It had the tentative brand name Trimesta. [37]

Related Research Articles

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

Quinestrol, also known as ethinylestradiol cyclopentyl ether (EECPE), sold under the brand name Estrovis among others, is an estrogen medication which has been used in menopausal hormone therapy, hormonal birth control, and to treat breast cancer and prostate cancer. It is taken once per week to once per month by mouth.

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

Estradiol acetate (EA), sold under the brand names Femtrace, Femring, and Menoring, is an estrogen medication which is used in hormone therapy for the treatment of menopausal symptoms in women. It is taken by mouth once daily or given as a vaginal ring once every three months.

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

Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy for menopausal symptoms and low estrogen levels, hormone therapy for transgender people, and in hormonal birth control. It is also used in the treatment of prostate cancer. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.

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

Polyestradiol phosphate (PEP), sold under the brand name Estradurin, is an estrogen medication which is used primarily in the treatment of prostate cancer in men. It is also used in women to treat breast cancer, as a component of hormone therapy to treat low estrogen levels and menopausal symptoms, and as a component of feminizing hormone therapy for transgender women. It is given by injection into muscle once every four weeks.

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

Mestranol, sold under the brand names Enovid, Norinyl, and Ortho-Novum among others, is an estrogen medication which has been used in birth control pills, menopausal hormone therapy, and the treatment of menstrual disorders. It is formulated in combination with a progestin and is not available alone. It is taken by mouth.

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.

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

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

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

Dienestrol diacetate is a synthetic nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol. It is an ester of dienestrol.

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

Diethylstilbestrol dipropionate (DESDP), or diethylstilbestrol dipropanoate, also known as stilboestrol dipropionate, is a synthetic nonsteroidal estrogen of the stilbestrol group that was formerly marketed widely throughout Europe. It is an ester of diethylstilbestrol with propionic acid, and is more slowly absorbed in the body than diethylstilbestrol. The medication has been said to be one of the most potent estrogens known.

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

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

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

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

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

Prasterone enanthate, also known as dehydroepiandrosterone enanthate (DHEA-E) and sold in combination with estradiol valerate under the brand name Gynodian Depot among others, is a weak androgen, estrogen, and neurosteroid medication which is used as a component of menopausal hormone therapy to treat menopausal symptoms in women. It is available only as an injectable preparation in combination with estradiol valerate. The medication is given by injection into muscle typically once every 4 weeks.

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

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

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

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

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

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

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

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

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

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

Polyestriol phosphate, sold under the brand names Gynäsan, Klimadurin, and Triodurin, is an estrogen medication which was previously used in menopausal hormone therapy and is no longer available.

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

Estriol phosphate (E3P), or estriol 17β-phosphate, also known as estra-1,3,5(10)-triene-3,16α,17β-triol 17β-(dihydrogen phosphate), is an estrogen which was never marketed. It is an estrogen ester, specifically an ester of estriol with phosphoric acid, and acts as a prodrug of estriol by cleavage via phosphatase enzymes in the body. Estriol phosphate is contained within the chemical structure of polyestriol phosphate, and this medication has been marketed for medical use.

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