Estriol succinate, sold under the brand name Synapause among others, is an

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

medication which is used in the treatment of

menopausal symptoms Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

, in through the vagina, and by

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

Medical uses

Estriol succinate is used in

menopausal hormone therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...

in the treatment and prevention of

such as

hot flash Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

es, vaginal atrophy, and osteoporosis. 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 Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus. Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of t ...

and endometrial cancer in women with intact

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The ...

es. 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.

Available forms

Estriol succinate is and has been available in the form of 2 and 4 mg

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or or ...

tablets, as a 0.1% vaginal

cream Cream is a dairy product composed of the higher-fat layer skimmed from the top of milk before homogenization. In un-homogenized milk, the fat, which is less dense, eventually rises to the top. In the industrial production of cream, this process ...

, and as a 20 mg

vial A vial (also known as a phial or flacon) is a small glass or plastic vessel or bottle, often used to store medication as liquids, powders or capsules. They can also be used as scientific sample vessels; for instance, in autosampler devices i ...

for use by

Side effects

Pharmacology

Estriol succinate is an

estrogen ester 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 estradio ...

, specifically, an

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

estriol Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estrone. Levels of estriol in women who are not pregnant are almost ...

, and acts as a prodrug of estriol in the body. It is described as a weak estrogen in comparison to

estradiol valerate Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 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 fo ...

. Estriol succinate is used medically via oral and vaginal routes similarly. In estriol succinate, two of the hydroxyl groups of estriol, those at the C16α and C17β positions, are esterified with

succinic acid Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

. As such, when adjusted for differences in

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

, a dose of 2 mg estriol succinate is equivalent to 1.18 mg unconjugated estriol. Unlike other estrogen esters, such as

, estriol succinate is hydrolyzed almost not at all in the

intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

mucosa when taken orally, and in relation to this, is absorbed more slowly than is estriol. Consequently, oral estriol succinate is a longer-acting form of estriol than oral estriol. Instead of in the gastrointestinal tract, oral estriol succinate is cleaved into estriol mainly in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

. 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.

Chemistry

Estriol succinate, also known as estriol disuccinate or as estriol 16α,17β-di(hydrogen succinate), is a synthetic

estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. '' Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, fo ...

steroid and a

derivative In mathematics, the derivative of a function of a real variable measures the sensitivity to change of the function value (output value) with respect to a change in its argument (input value). Derivatives are a fundamental tool of calculus. ...

. It is specifically the C16α and C17β disuccinate

of estriol. The medication is provided both as estriol succinate and as estriol sodium succinate, the

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

. Other marketed estriol esters besides estriol succinate include

estriol acetate benzoate Estriol acetate benzoate () (brand name Holin-Depot), or oestriol diacetate benzoate (), is an estrogen medication. It is an estrogen ester An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens ...

and

estriol tripropionate Estriol tripropionate (brand name Estriel), or estriol tripropanoate, is an estrogen medication. It is an estrogen ester, specifically, an ester of estriol Estriol (E3), also spelled oestriol, is a steroid, a weak estrogen, and a minor female ...

, whereas estriol dihexanoate, estriol dipropionate, and estriol triacetate are estriol esters that were never marketed. Quinestradol is an estriol ether and has also been marketed. Polyestriol phosphate is an ester of estriol in the form of a

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

, and was previously marketed.

History

Estriol succinate was introduced for medical use in 1966.

Society and culture

Generic names

''Estriol succinate'' is the generic name of the drug and its and . Other synonyms include ''oestriol succinate'', ''estriol disuccinate'', and ''estriol hemisuccinate''. When provided as the sodium salt, estriol succinate is known as ''estriol sodium succinate'' () or as ''oestriol sodium succinate''.

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. Estriol sodium succinate has been marketed specifically under the brand names Pausan and Styptanon.

Availability

Estriol succinate is or has been marketed in

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirel ...

Hong Kong Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China (abbr. Hong Kong SAR or HKSAR), is a city and special administrative region of China on the eastern Pearl River Delta i ...

, and

Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...

Research

Estriol succinate was under development for the treatment of multiple sclerosis in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

and worldwide, and reached phase II

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s for this indication, but development was discontinued due to insufficient effectiveness. It had the tentative brand name Trimesta.

References

{{Estrogen receptor modulators Estriol esters Estrogens Phenols Succinate esters Triols