Polyestriol phosphate explained

Polyestriol phosphate (PE3P, SEP), sold under the brand names Gynäsan, Klimadurin, and Triodurin, is an estrogen medication which was previously used in menopausal hormone therapy (i.e., to treat menopausal symptoms in postmenopausal women) and is no longer available.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]

Medical uses

PE3P has been used at a dosage of 40 to 80 mg by intramuscular injection once every 4 to 8 weeks in menopausal hormone therapy.

Available forms

PE3P has been available in the form of ampoules containing 50 to 80 mg in 1 or 2 mL aqueous solution.[13] [14] [15]

Pharmacology

PE3P is similar to polyestradiol phosphate (PEP), and is, likewise, an estrogen ester – specifically, an ester and prodrug of estriol – in the form of a polymer with phosphate linkers. When adjusted for differences in molecular weight, PE3P contains the equivalent of about 80% of the amount of estriol. As such, 40 mg PE3P corresponds to about 32 mg estriol. Doses of PE3P of 10 mg or more have an extended duration of action. A single intramuscular injection of 80 mg PE3P has a duration of about 1 month and of 80 mg about 2 months.

The effects of PE3P on the vagina, uterus, pregnancy, prostate gland, coagulation, and fibrinolysis, as well as on mammary and endometrial cancer risk, have been studied.[16] [17] [18] [19] [20] [21] [22] [23] [24] The endometrial proliferation dose of PE3P over 14 days in women is 40 to 60 mg by intramuscular injection.

Chemistry

PE3P is a water-soluble polymer of estriol with phosphoric acid.

History

PE3P was developed by the Swedish pharmaceutical company Leo Läkemedel AB in the 1960s.[25] It was introduced for medical use by 1968.[26] [27]

Society and culture

Brand names

PE3P was marketed under brand names including Gynäsan, Klimadurin, and Triodurin.[28]

Availability

PE3P was marketed in Germany and Spain.[29]

See also

Notes and References

  1. Konyves I . En vattenloslig ostriolpolymer-polyostriolfosfat . A water-soluble estriol polymer-polyestriol phosphate . Tidsskrift for Kjemi Bergvesenog Metallurgi . January 1965 . 25 . 12 . 288 .
  2. Lauritzen C, Velibese S . Clinical investigations of a long-acting oestriol (polyoestriol phosphate) . Acta Endocrinologica . 38 . 1 . 73–87 . September 1961 . 13759555 . 10.1530/acta.0.0380073 .
  3. Lauritzen C . [Experience with an injectionable estriol Depot preparation. (Gynaesan pro injectione)] . de . Munchener Medizinische Wochenschrift . 110 . 19 . 1203–1206 . May 1968 . 5695211 .
  4. Bachmann FF . [Treatment of menopausal complants with polyoestriol-phosphate. Experiences with Gynäsan injections] . de . Munchener Medizinische Wochenschrift . 113 . 5 . 166–169 . January 1971 . 5107471 . Treatment of menopausal complants with polyoestriol-phosphate. Experiences with Gynäsan injections .
  5. Book: Labhart A . Clinical Endocrinology: Theory and Practice. 6 December 2012. Springer Science & Business Media. 978-3-642-96158-8. 551–. 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..
  6. Book: Negwer M, Scharnow HG . Organic-chemical drugs and their synonyms: (an international survey). 4 October 2001. Wiley-VCH. 978-3-527-30247-5. 8075-01 (6628-01) 37452-43-0 R Polymeric ester with phosphoric acid S Klimadurin, Polyestriol phosphate, Polyostriolphosphat, Triodurin U Depot-estrogen.
  7. Book: Martindale W, ((Royal Pharmaceutical Society of Great Britain. Dept. of Pharmaceutical Sciences)). The Extra Pharmacopoeia. 1993. Pharmaceutical Press. 978-0-85369-300-0. 2258. Polyoestriol Phosphate. [...] ingredient of Klimadurin. [...] Triodurin [...]..
  8. Book: Archiv für Gynäkologie. 1971. Polyoestriol phosphat. Gynäsan (R) pro injectione, 50 mg als Depot.. 206.
  9. Book: Ars Medici. 1971. 194–196, 408, 786. Klinik in Lund die wirküng von Östriol an einem Urethritismaterial untersucht. Bei dem Präparat, Triodurin1-Leo, das bei der Prüfung verwendet wurde, handelt es sich um ein Polyöstriolphosphat, ein Polyester aus östra-1,3,5(10)-triene-3,16α,17β-triol und Phosphorsäure. Das östriolmolekül wurde mittels Phosphorsäurebrücken in die polymere Form gebracht, und das Molekül ent-hält eine grosse Zahl von Östrioleinheiten (Kön vves, 1965). Das Präparat besitzt [...] Behandlung und Ergebnisse Sämtliche Patientinnen erhielten etwa jeden 2. Monat 50-80 mg Poly-ostriolphosphat. Die Frauen reagierten fast ausnahmslos zufriedenstellend auf diese Behandlung. Die meisten gaben spontane Besserung ihrer übrigen klimak- [...] Eigenschaften Klimadurin F. Ist ein aus natürlichem Oestriol gewonnenes Depot-östrogen. Das wasserlösliche, aber inaktive polymerisierte östriol-phosphat wird durch langsamen Abbau als biologisch wirksame Form kontinuierlich freigesetzt. Die östrogene Wirkung äussert sich fast ausschliesslich in einer Stimullerung der Cervixdrüsen und der Proli- [...].
  10. Lauritzen C . Clinical use of oestrogens and progestogens . Maturitas . 12 . 3 . 199–214 . September 1990 . 2215269 . 10.1016/0378-5122(90)90004-P .
  11. Book: Utian WH . The Menopause Manual: A woman's guide to the menopause. 6 December 2012. Springer Science & Business Media. 978-94-011-7135-9. 58–.
  12. Book: Campbell S . 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. 6 December 2012. Springer Science & Business Media. 978-94-011-6165-7. 395–. 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..
  13. Book: Saure A . Die Wechseljahre der Frau: Hormone — Präparate — Therapien. 11 November 2013. Springer-Verlag. 978-3-0348-6676-7. 156–. Polyestriol phosphate 50 mg*** and 80 mg/1 ml*** and 2 ml solution for injection = 1 ampoule (Klimadurin*, Triodurin***). Recommended dosage: 1 ampoule in the muscle every 6–8 weeks..
  14. Book: Lauritzen C . Natürliche und Synthetische Sexualhormone – Biologische Grundlagen und Behandlungsprinzipien . 229–306 . Natural and Synthetic Sexual Hormones – Biological Basis and Medical Treatment Principles . Schneider HP, Lauritzen C, Nieschlag E . Grundlagen und Klinik der Menschlichen Fortpflanzung . Foundations and Clinic of Human Reproduction . de . 1988 . Walter de Gruyter . 978-3110109689 . 35483492 .
  15. Lauritzen C . Grundlagen der hormonalen Therapie klimakterischer Beschwerden . Basics of Hormonal Therapy for Menopausal Symptoms . Deutsches Ärzteblatt . 23 January 1975 . 72 . 4 . 205–212 . 0012-1207 .
  16. Sjöstedt S, Strandh J . Effect of polyestriol phosphate on the vaginal cytology and uterine endometrium of postmenopausal women . Acta Obstetricia et Gynecologica Scandinavica Supplement . 9 . Suppl 9 . Suppl 9:30 . 1971 . 5287101 . 10.3109/00016347109161433 . 73354582 .
  17. Purola E, Vartiainen E . Effect of long-acting oestriol on the vaginal cytology of postmenopausal women . Annales Chirurgiae et Gynaecologiae . 66 . 4 . 216–218 . 1977 . 907314 .
  18. Fredholm B, Lindskog M . Some effects of a long-acting estriol polymer, polyestriol phosphate . Acta Physiologica Scandinavica . 74 . January 1969 . 2018-11-11 . 2019-08-22 . https://web.archive.org/web/20190822125508/https://www.popline.org/node/478317 . dead .
  19. Müntzing J . Effects of polymerized oestrogens on the ventral prostate in rats . Acta Pharmacologica et Toxicologica . 27 . 6 . 417–423 . 1969 . 5395730 . 10.1111/j.1600-0773.1969.tb00488.x .
  20. Lutwak-Mann C, Hay MF . Effect of certain water-soluble oestrogens on rabbit blastocysts . Journal of Endocrinology . 30 . 4 . ix-x . 1964 . 2018-11-11 . 2019-08-22 . https://web.archive.org/web/20190822125508/https://www.popline.org/node/478317 . dead .
  21. Andersson M, Müntzing J . Effects of oestrogen on phosphatase activity in the ventral prostate of intact, castrated, and androgen-treated castrated, adult rats . Acta Pharmacologica et Toxicologica . 30 . 3 . 193–202 . 1971 . 5171939 . 10.1111/j.1600-0773.1971.tb00650.x .
  22. Gjønnaess H, Munkeby I, Frølich W, Vennerød AM, Fagerhol MK . Effect of estrogen treatment on coagulation and fibrinolysis in postmenopausal women. With special reference to cold activation of factor VII . Gynecologic and Obstetric Investigation . 9 . 2–3 . 109–123 . 1978 . 738649 . 10.1159/000300974 .
  23. Book: Lauritzen C, Meier F . The Climacteric: An Update. Risks of endometrial and mammary cancer morbidity and mortality in long-term oestrogen treatment. 1984. 207–216. Springer . 10.1007/978-94-009-5608-7_20. 978-94-010-8973-9.
  24. Terenius L . Effect of anti-oestrogens on initiation of mammary cancer in the female rat . European Journal of Cancer . 7 . 1 . 65–70 . February 1971 . 5576730 . 10.1016/0014-2964(71)90096-X .
  25. Johnson W . Therapeutic Trends. American Journal of Health-System Pharmacy. 19. 3. 1962. 136. 1079-2082. 10.1093/ajhp/19.3.136.
  26. Book: Svensk Farmaceutisk Tidskrift. 1973. Sveriges Apotekareförbunds. 713, 728. Ibland är de postmenopausala besvären så uttalade att östrogenbehandling kan anses befogad. Leo har för denna terapi introducerat Triovex (1960) och det långverkande polyöstriolfosfatet Triodurin (1968). [...] Med andra ord, i Triodurin är östriolmolekyler kopplade med fosforsyrabryggor till en polymer.» Vilka kliniska erfarenheter har man av Triodurin? »Erfarenheterna har visat att Triodurin är särskilt lämpligt vid östrogenbehandling när man vill [...] 1968 TRIODURIN Estriol som genom forsforsyrebryggor bringats i polymer form och därigenom ger en prolongerad effekt..
  27. Arnold M . [Treatment of climacteric complannt with Klimadurin] . de . Praxis . 58 . 37 . 1159–1162 . September 1969 . 5820318 . Treatment of climacteric complaint with Klimadurin .
  28. Book: Revue Médicale de la Suisse Romande . 1972 . H. Georg . 780 .
  29. Book: Drugs Available Abroad. 1991. Gale Research. 978-0-8103-7177-4. 176. 790 * POLYESTRIOL PHOSPHATE Countries Where Available and Release Dates: Spain (1971). Brand Names and Manufacturers: • Klimadurin — Pharmacia Iberica (Spain) Drug Action: Estrogen. Indications/Usage: Menopausal symptoms; postmenopausal symptoms; posthysterectomy symptoms; estrogen replacement. How Supplied: 80 mg vials. Dosage: 80 mg every 4-8 weeks I.M. Precautions/Warnings: Biliary tract disease; endometriosis; uterine fibroma; hypercalcemia associated with tumors or metabolic bone disease; porphyria. Contraindications: Mammary tumors; estrogen-dependent tumors; history of cholestatic icterus; thrombophlebitis; thrombosis; thromboembolic disturbances; vaginal bleeding; pregnancy; lactation. Interactions: Oral anticoagulants; rifampin. [...] U.S. Treatments: Conjugated estrogens are commonly prescribed for menopausal symptoms in the U.S..

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