Conjugated estriol, sold under the brand namesProgynon andEmmenin, is anestrogen medication which was previously used for estrogen-type indications such as the treatment ofmenopausal symptoms in women. The term specifically refers toformulations ofestriol conjugates which were manufactured from the estrogen-richurine ofpregnant women and were used as medications in the 1920s and 1930s. Conjugated estriol is analogous to and was superseded byconjugated estrogens (brand name Premarin), which is manufactured from the urine of pregnantmares. Conjugated estriol was among the first forms ofpharmaceutical estrogen to be used in medicine. It was takenby mouth.
The main components of conjugated estriol areestriol glucuronides and to a lesser extentestriol sulfates. Estrogen glucuronides can be deglucuronidated into the corresponding free estrogens byβ-glucuronidase intissues that express thisenzyme, such as themammary gland,liver, andkidney, among others.[1] Likewise, estrogen sulfates can be desulfated into the corresponding free estrogens bysteroid sulfatase in tissues that express this enzyme.[2] Consequently, estrogen conjugates have estrogenic activity via conversion into unconjugated estrogens.[1]
To further reduce the costs of manufacturing Progynon, Schering eventually switched to using the urine of pregnantmares and called its new product Progynon 2.[3][4][11] Ayerst followed suit, with the introduction ofPremarin (conjugated equine estrogens) in 1941.[4] Premarin soon superseded Emmenin and has since become not only a very widely used estrogen, but one of the most widely prescribed drugs inNorth America.[12]
Both Progynon and Emmenin contained a mixture ofwater-soluble estrogens, which was determined later to be mostlyestriol glucuronide.[4][13]Conjugates ofestriol like estriol glucuronide andestriol sulfate constitute more than 90% of the estrogens in the urine of pregnant women.[14] Of these conjugates, 35 to 46% are estriol glucuronides and 15 to 22% are estriol 3-sulfate in late pregnancy; the double conjugateestriol sulfate glucuronide (probably estriol 3-sulfate 16α-glucuronide) also occurs.[15][16][17]
Progynon was also the name that Butenandt originally gaveestrone (which he had isolated in 1929) in his first publication on the substance (and later referred to as folliculine, with the name estrone not finally being adopted until 1935).[18][19] Aside from Progynon and Progynon 2, the Progynon name has also been used in a variety of other estrogenic products marketed by Schering, including Progynon-B (estradiol benzoate), Progynon-DH (estradiol; "dihydroxyestrin"), Progynon-DP (estradiol dipropionate), Progynon-C (ethinylestradiol), Progynova (estradiol valerate), and Progynon Depot (estradiol valerate,estradiol undecylate).
To reduce the costs of manufacturing Emmenin and Progynon, Ayerst and Schering eventually switched to using the urine of pregnantmares (which containsconjugated equine estrogens, primarilyestrone sulfate)[2] and called their new productsPremarin and Progynon 2, respectively.[3][4][11] Premarin was introduced by Ayerst in 1941[4] and has become not only a very widely used estrogen, but one of the most widely prescribed drugs inNorth America.[12]
Both Emmenin and Progynon contained a mixture ofwater-solubleconjugated estrogens, later determined to be mostlyestriol glucuronide.[4][13]Conjugates ofestriol like estriol glucuronide andestriol sulfate constitute more than 90% of the estrogens in the urine of pregnant women.[14] Of these conjugates, 35 to 46% are estriol glucuronides and 15 to 22% are estriol 3-sulfate in late pregnancy; the double conjugateestriol sulfate glucuronide (probably estriol 3-sulfate 16α-glucuronide) also occurs.[15][16][17] Unlike unconjugated estrogens likeestradiol andestrone, these estrogens were orally active.[4][8][26][27]
^abStreck A (1928). ""Progynon"-Schering, ein Neues Zyklus-Hormonpräparat" ["Progynon"-Schering, a new cycle hormone preparation].Klinische Wochenschrift (in German).7 (25):1172–1178.doi:10.1007/BF01738283.ISSN0023-2173.S2CID35945534.
^Batisweiler J (1928). "Placentaextrakt Progynon (Schering-Kahlbaum) bei Menstruationsstörungen und Kastrationsfolgen" [Placenta extract Progynon (Schering-Kahlbaum) for menstrual disorders and the consequences of castration.].ZBL. Gynäk (in German):2227–2232.
^Booth D (2 November 1983)."Estrone". In Florey K (ed.).Analytical Profiles of Drug Substances. Vol. 12. Academic Press. pp. 136–.ISBN978-0-08-086107-4.
^Macfarlane C (1936). "Observations on the use of Collip's emmenin in the menopause".American Journal of Obstetrics and Gynecology.31 (4):663–666.doi:10.1016/S0002-9378(36)90468-4.ISSN0002-9378.
^Campbell AD, Collip JB (1930). "Treatment of menopausal symptoms and menstrual disorders with extracts of human placenta and pregnancy urine".Canadian Medical Association Journal.23:633–641.
