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]
Estriol succinate is anestrogen ester, specifically, anester ofestriol, and acts as aprodrug of estriol in the body.[7][1] It is described as a weak estrogen in comparison toestradiol valerate.[1][8] Estriol succinate is used medically via oral and vaginal routes similarly.[1] In estriol succinate, two of thehydroxyl groups of estriol, those at the C16α and C17β positions, are esterified withsuccinic acid.[1] As such, when adjusted for differences inmolecular weight, a dose of 2 mg estriol succinate is equivalent to 1.18 mg unconjugated estriol.[1] Unlike other estrogen esters, such asestradiol valerate, estriol succinate ishydrolyzed almost not at all in theintestinalmucosa 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 thegastrointestinal tract, oral estriol succinate iscleaved into estriol mainly in theliver.[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]
Estriol succinate is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name andBANTooltip British Approved Name.[7][29][36][30][35] Other synonyms includeoestriol succinate,estriol disuccinate, andestriol hemisuccinate.[7][29][36][30] When provided as the sodium salt, estriol succinate is known asestriol sodium succinate (BANTooltip British Approved Name) or asoestriol sodium succinate.[7][29]
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]
Estriol succinate was under development for the treatment ofmultiple sclerosis in theUnited States and worldwide, and reachedphase IIclinical trials for this indication, but development was discontinued due to insufficient effectiveness.[37] It had the tentative brand name Trimesta.[37]
^Lauritzen C (November 1987). "Results of a 5 years prospective study of estriol succinate treatment in patients with climacteric complaints".Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Métabolisme.19 (11):579–584.doi:10.1055/s-2007-1011886.PMID3428874.S2CID10551484.
^Clark JH, Markaverich BM (1983). "The agonistic and antagonistic effects of short acting estrogens: a review".Pharmacology & Therapeutics.21 (3):429–453.doi:10.1016/0163-7258(83)90063-3.PMID6356176.
^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.PMID559617.
^Lauritzen CH (January 1976). "The female climacteric syndrome: significance, problems, treatment".Acta Obstetricia Et Gynecologica Scandinavica. Supplement.51:47–61.doi:10.3109/00016347509156433.PMID779393.
^Lauritzen C (1975). "The Female Climacteric Syndrome: Significance, Problems, Treatment".Acta Obstetricia et Gynecologica Scandinavica.54 (s51):48–61.doi:10.3109/00016347509156433.ISSN0001-6349.
^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.PMID15432047.
^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.PMID14902290.
^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.ISSN0001-6349.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.
^Martinez-Manautou J, Rudel HW (1966). "Antiovulatory Activity of Several Synthetic and Natural Estrogens". In Robert Benjamin Greenblatt (ed.).Ovulation: Stimulation, Suppression, and Detection. Lippincott. pp. 243–253.
^Herr F, Revesz C, Manson AJ, Jewell JB (1970). "Biological Properties of Estrogen Sulfates".Chemical and Biological Aspects of Steroid Conjugation. pp. 368–408.doi:10.1007/978-3-642-49793-3_8.ISBN978-3-642-49506-9.
^Lauritzen C, Velibese S (September 1961). "Clinical investigations of a long-acting oestriol (polyoestriol phosphate)".Acta Endocrinologica.38 (1):73–87.doi:10.1530/acta.0.0380073.PMID13759555.
^Bachmann FF (January 1971). "[Treatment of menopausal complants with polyoestriol-phosphate. Experiences with Gynäsan injections]" [Treatment of menopausal complaints with polyoestriol-phosphate. Experiences with Gynäsan injections].Munchener Medizinische Wochenschrift (in German).113 (5):166–169.PMID5107471.
^Labhart A (6 December 2012).Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 548, 551.ISBN978-3-642-96158-8.The polymer of estradiol or estriol and phosphoric acid has an excellent depot action when given intramuscularly (polyestriol phosphate or polyestradiol phosphate) (Table 16). Phosphoric acid combines with the estrogen molecule at C3 and C17 to form a macromolecule. The compound is stored in the liver and spleen where the estrogen is steadily released by splitting off of the phosphate portion due to the action of alkaline phosphatase. [...] Conjugated estrogens and polyestriol and estradiol phosphate can also be given intravenously in an aqueous solution. Intravenous administration of ovarian hormones offers no advantages, however, and therefore has no practical significance. [...] The following duarations of action have been obtained with a single administration (WlED, 1954; LAURITZEN, 1968): [...] 50 mg polyestradiol phosphate ~ 1 month; 50 mg polyestriol phosphate ~ 1 month; 80 mg polyestriol phosphate ~ 2 months.
^Campbell S (6 December 2012).The Management of the Menopause & Post-Menopausal Years: The Proceedings of the International Symposium held in London 24–26 November 1975 Arranged by the Institute of Obstetrics and Gynaecology, The University of London. Springer Science & Business Media. pp. 395–.ISBN978-94-011-6165-7.In the Federal Republic of Germany between 10 and 20% of all climacteric women are on estrogen treatment. We have the following oral estrogens for a treatment. (t) Conjugated estrogens, (2) estradiol valerate, (3) ethinyl-estradiol and its cyclopentyl-enol ether, (4) stilbestrol, (5) ethinyl-estradiol-methyltestosterone, (6) estriol and estriol succinate, most of them as coated tablets. Several long acting injectable preparations are available: several esters of combined estradiol-testosterone, one of estradiol-dehydroepiandrosterone enanthate and a prolonged polyestriol phosphate are also available. Lastly, depot injections of estradiol- and stilbestrol-esters are on the market.
