Conjugated estriol, sold under the brand names Progynon and Emmenin, is an
estrogen medication which was previously used for estrogen-type indications such as the treatment of
menopausal symptoms in women. The term specifically refers to
formulations of
estriol conjugates which were manufactured from the estrogen-rich
urine of
pregnant women and were used as medications in the 1920s and 1930s. Conjugated estriol is analogous to and was superseded by
conjugated estrogens (brand name Premarin), which is manufactured from the urine of pregnant
mares. Conjugated estriol was among the first forms of
pharmaceutical estrogen to be used in medicine. It was taken
by mouth.
The main components of conjugated estriol are
estriol glucuronides and to a lesser extent
estriol sulfates. Estrogen glucuronides can be deglucuronidated into the corresponding free estrogens by
β-glucuronidase in
tissues that express this
enzyme, such as the
mammary gland,
liver, and
kidney, among others.[1] Likewise, estrogen sulfates can be desulfated into the corresponding free estrogens by
steroid 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 pregnant
mares and called its new product Progynon 2.[3][4][11] Ayerst followed suit, with the introduction of
Premarin (
conjugated equine estrogens) in 1941.[4] Premarin soon superseded Emmenin and has since become not only a very widely used estrogen, but one of the most widely prescribed drugs in
North America.[12]
Both Progynon and Emmenin contained a mixture of
water-soluble estrogens, which was determined later to be mostly
estriol glucuronide.[4][13]Conjugates of
estriol like estriol glucuronide and
estriol 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 conjugate
estriol sulfate glucuronide (probably estriol 3-sulfate 16α-glucuronide) also occurs.[15][16][17]
Progynon was also the name that Butenandt originally gave
estrone (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 pregnant
mares (which contains
conjugated equine estrogens, primarily
estrone sulfate)[2] and called their new products
Premarin 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 in
North America.[12]
Both Emmenin and Progynon contained a mixture of
water-solubleconjugated estrogens, later determined to be mostly
estriol glucuronide.[4][13]Conjugates of
estriol like estriol glucuronide and
estriol 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 conjugate
estriol sulfate glucuronide (probably estriol 3-sulfate 16α-glucuronide) also occurs.[15][16][17] Unlike unconjugated estrogens like
estradiol and
estrone, 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.