Estradiol benzoate was discovered in 1933 and was introduced for medical use that same year.[4][18][19][20][21][22][23] It was the first estradiol ester to be discovered or marketed, and was one of the first estrogens to be used in medicine.[24] Along with estradiol dipropionate, estradiol benzoate was among the most widely used esters of estradiol for many years following its introduction.[25] However, in the 1950s, longer-acting estradiol esters that necessitated less frequent injections, such as estradiol valerate and estradiol cypionate, were developed, and have since largely superseded estradiol benzoate.[9] Nonetheless, estradiol benzoate remains widely available throughout the world.[15] It is not available for medical use in the United States, but is available there for use in veterinary medicine.[26][27]
Estradiol benzoate has a relatively short duration of action, and is administered by intramuscular injection usually two to three times per week.[8][12] It is used in the treatment of menopausal symptoms at a dosage of 1 to 1.66 mg initially and 0.33 to 1 mg for maintenance two times per week, and in the treatment of hypoestrogenism and delayed puberty at a dosage of 1.66 mg two to three times per week.[8][30] The dosage used in hormone therapy for transgender women is 0.5 to 1.5 mg two to three times per week.[13] In the treatment of prostate cancer, estradiol benzoate is used at a dosage of 1.66 mg three times per week (for a total of 5 mg per week).[8]
Footnotes:a = No longer used or recommended, due to health concerns. b = As a single patch applied once or twice per week (worn for 3–4 days or 7 days), depending on the formulation. Note: Dosages are not necessarily equivalent. Sources: See template.
Estradiol benzoate is and has been available as an oil solution for intramuscular injection provided as vials and ampoules at concentrations of 0.167, 0.2, 0.33, 1, 1.67, 2, 5, 10, 20, and 25 mg/mL.[23][31][8] It is also available as a microcrystallineaqueous suspension for intramuscular injection under the brand name Agofollin Depot.[32][33][34][28]Sistocyclin was the brand name of a product containing 10 mg microcrystalline estradiol benzoate and 200 mg microcrystalline progesterone in an aqueous suspension.[35][36][37][38]Follivirin (and previously Femandren M) is the brand name of a product containing 2.5 mg microcrystalline estradiol benzoate and 25 to 50 mg microcrystalline testosterone isobutyrate in aqueous suspension.[39][40][41][42]
^This table includes primarily products available as a single-ingredient estradiol preparation—thus excluding compounds with progestogens or other ingredients included. The table furthermore does not include compounded drugs—only commercially produced products. Availability of each product varies by country.
^Doses are given per unit (ex: per tablet, per mL).
^Other brand names may be manufactured or previously manufactured.
Estradiol benzoate is an estradiol ester, or a prodrug of estradiol.[4][5] As such, it is an estrogen, or an agonist of the estrogen receptors.[4][5] Estradiol benzoate has very low affinity for the ERs, on the order of 100-fold less than that of estradiol.[64] As such, estradiol benzoate is regarded as essentially inactive in terms of estrogenic effect itself, acting solely as a prodrug to estradiol.[5] Estradiol benzoate is of about 38% higher molecular weight than estradiol due to the presence of its C3 benzoate ester.[65][15] Because estradiol benzoate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.[4]
In the case of intramuscular injections of either estradiol benzoate or estradiol valerate in oil solution, the maturation dosage for the vaginalepithelium is 5 to 7 mg once per week and the endometrialproliferation dosage is 7 to 10 mg once per week.[66] The total endometrial proliferation dosage of estradiol benzoate in oil solution by intramuscular injection over 14 days is 25 to 35 mg.[67][10][11]
The full endometrial transformation dosage of estradiol benzoate/progesterone in oil solution is 1 to 2 mg estradiol benzoate and 20 to 25 mg progesterone by intramuscular injection daily for 10 to 14 days, whereas the full endometrial transformation dosage of estradiol benzoate/progesterone in microcrystalline aqueous suspension is a single intramuscular injection of 10 mg estradiol benzoate and 200 mg progesterone.[66] For comparison, the full endometrial transformation dosage of estradiol valerate and hydroxyprogesterone caproate in oil solution (brand name Gravibinon) is a single intramuscular injection of 10 mg estradiol valerate and 250 to 375 mg hydroxyprogesterone caproate.[66] Endometrial transformation normally occurs during the luteal phase of the menstrual cycle; it is induced by endogenous progesterone following adequate priming by endogenous estradiol.[68]
The decidua (pregnancy-type endometrium) induction dosage of estradiol benzoate/progesterone in oil solution is 2 to 5 mg estradiol benzoate and 20 to 100 mg progesterone by intramuscular injection daily for 5 to 7 weeks, whereas the decidua induction dosage of estradiol benzoate/progesterone in microcrystalline aqueous suspension is 10 to 20 mg estradiol benzoate and 200 to 250 mg progesterone in microcrystalline aqueous suspension by intramuscular injection once per week for about 6 weeks.[66] For comparison, the decidua induction dosage of estradiol valerate and hydroxyprogesterone caproate in oil solution is about the same as that of microcrystalline estradiol benzoate/progesterone in aqueous suspension.[66] The decidua induction dosages of estrogen and progestogen combinations are pseudopregnancy dosages.[66]
Levels of estradiol, testosterone, and gonadotropins with 4.5μg/kg injectable estradiol benzoate every 12hours (or ~0.63mg/day for a 70-kg [154-lb] person) in transgender women.[69]
As with other estrogens and forms of estradiol,[70][71][72] estradiol benzoate dose-dependently suppresses gonadotropin and testosterone levels in men and transgender women.[69] In a study that administered estradiol benzoate twice-daily to transgender women at a dose that resulted in measured estradiol levels of about 200 to 250pg/mL, testosterone levels decreased from around 530ng/dL at baseline to about 55ng/dL (–90%) within approximately 3days of treatment.[69]
Following administration, estradiol benzoate acts as a prodrug of estradiol via cleavage by esterases into estradiol and the natural fatty acidbenzoic acid.[5] This cleavage occurs not only in the liver, but also in the blood and in tissues.[4][5] Esters of estradiol like estradiol benzoate are readily hydrolyzed to estradiol, but have an extended duration when administered in via intramuscular or subcutaneous injection due to a depot effect afforded by their fatty acid ester moiety and consequent high lipophilicity.[5] A long-lasting local tissue depot is formed by the injection that slowly releases estradiol benzoate into the circulation.[5]
Intramuscular injection
Oil solution
The duration of action of estradiol benzoate in oil solution by intramuscular injection at typical clinical doses (e.g., 0.33–1.66 mg) is said to be 2 to 3 days.[7][8] A single dose of 2.5 mg estradiol benzoate in oil solution by intramuscular injection was found to produce plasma estradiol levels of greater than 400 pg/mL, measured 24 hours post-injection, in a group of patients with minimal baseline levels of estradiol (due to GnRH analogue therapy with triptorelin).[73] The elimination half-life of estradiol benzoate in oil solution by intramuscular injection has been reported to be 48 to 120 hours (2 to 5 days).[6]
A single intramuscular injection of 5 mg estradiol benzoate in oil solution has been found to result in peak circulating concentrations of 940 pg/mL estradiol and 343 pg/mL estrone, which occurred at about 2 days post-injection.[9] Compared to two other commonly used estradiol esters, estradiol benzoate had the shortest duration, at approximately 4 to 5 days, whereas estradiol valerate and estradiol cypionate were found to last for 7 to 8 days and 11 days, respectively.[9] This is because estradiol benzoate has a shorter and less bulky fatty acidchain, and in relation to this, is comparatively less lipophilic.[5] For a given estradiol ester, the shorter or less bulky the fatty acid chain is, the less lipophilic, shorter-lasting, and less uniform/plateau-like the resultant levels of estradiol are as well as the higher (and hence more spike-like) the peak/maximal levels are.[5]
Daily intramuscular injections of 1 mg estradiol benzoate in oil solution have been found to produce estradiol excretion rates almost double those of the normal luteal phase.[66][74][75] This is in accordance with known production rates of estradiol in women (e.g., 300 μg/day in the luteal phase).[66][76]
Hormone levels with estradiol benzoate by intramuscular injection
Estradiol levels after single intramuscular injections of 0.5, 1.5, or 2.5 mg estradiol benzoate in oil in 5 premenopausal women each.[77] Assays were performed using radioimmunoassay.[77] Source was Shaw et al. (1975).[77]
Estradiol levels after single intramuscular injections of 5 mg of different estradiol esters in oil in about 10 premenopausal women each.[9] Assays were performed using radioimmunoassay with chromatographic separation.[9] Source was Oriowo et al. (1980).[9]
Estradiol levels after a short intravenous infusion of 20 mg estradiol in aqueous solution or an intramuscular injection of equimolar doses of estradiol esters in oil solution in postmenopausal women.[78][79] Assays were performed using RIA with CS.[78][79] Source was Geppert (1975).[78][79]
Simplified curves of estradiol levels after injection of different estradiol esters in women.[80] Source was Garza-Flores (1994).[80]
Vaginalcornification with a single intramuscular injection of different estradiol esters in oil solution in women.[25] Source was Schwartz & Soule (1955).[25]
Estradiol benzoate is active with oral and sublingual administration, similarly to estradiol valerate and estradiol acetate.[7][88]: 310 However, it is not marketed in any formulation for use by these routes.[23] Oral estradiol benzoate has been reported to possess about one-third to half the potency of intramuscular injection of estradiol benzoate.[95][96][97][98] This level of oral potency has been described as remarkably high.[96] The sublingual potency of estradiol benzoate is similar to that of estradiol.[88]: 310 A study found that the total dose of estradiol benzoate needed for endometrial proliferation in women was 60 to 140 mg, relative to 60 to 180 mg for estradiol.[88]: 310 Both estradiol and estradiol benzoate has a persistence of estrogenic effect with single administration of one day.[88]: 310
Estradiol benzoate was one of the first estrogens to be developed and marketed.[21] In 1932, Adolf Butenandt described estrone benzoate and reported that it had a prolonged duration of action.[11][102] Schwenk and Hildebrant at Schering discovered estradiol via reduction of estrone in 1933, and they proceeded to synthesize estradiol benzoate from estradiol the same year.[4][18] Estradiol benzoate was patented by Schering in 1933 and was introduced in an oil solution for use by intramuscular injection under the brand name Progynon B that year as well.[19][20][21][22][23] By 1936, multiple formulations of estradiol benzoate in oil solution had been marketed, including under the brand names Progynon B by Schering, Dimenformon Benzoate by Roche-Organon, and Oestroform B by British Drug Houses.[103][104][105][106][107][108][109] By the early 1940s, Ben-Ovocylin had been introduced by Ciba as well.[104][105][106] In the late 1940s, the brand name Ben-Ovocylin was changed by Ciba to Ovocylin Benzoate.[110] Following their introduction, estradiol benzoate and estradiol dipropionate were the most widely used esters of estradiol for many years.[25] However, estradiol valerate and estradiol cypionate, which are longer-acting esters that require less frequent administration, were developed and introduced in the 1950s, and have since largely superseded estradiol benzoate and estradiol dipropionate.[9]
Society and culture
Generic names
Estradiol benzoate is the generic name of the drug and its INNTooltip International Nonproprietary Name, BANMTooltip British Approved Name, and JANTooltip Japanese Accepted Name, while oestradiol benzoate was formerly its BANMTooltip British Approved Name.[14][15][65][100]
Brand names
The major brand name of estradiol benzoate is Progynon-B.[15][65][100] It has also been sold under a variety of other brand names including Agofollin Depot, Ben-Ovocylin, Benzhormovarine, Benzoestrofol, Benzofoline, Benzo-Ginestryl, Benzo-Ginoestril, Benzo-Gynoestryl, Benzoate d'oestradiol P.A. Intervet, Benztrone, Benztrone Pabyrn, Diffollisterol, Di-Folliculine, Dimenformon, Dimenformon Benzoate, Dimenformone, Diogyn B, EBZ, Eston-B, Estradiolo Amsa, Femestrone, Follicormon, Follidrin, Graafina, Gynecormone, Gynecormone Gouttes, Gynformone, Metroval, Hidroestron, Hormogynon, Oestradiol Benzoat, Oestradiol-Benzoat Intervet, Oestradiol-K Streuli, Oestradiolium Benzoicum, Oestraform, Ostrin, Ovahormon Benzoate, Ovasterol-B, Ovex, Ovocyclin Benzoate, Ovocyclin M, Primogyn B, Primogyn B Oleosum, Primogyn I, Progynon Benzoate, Recthormone, Oestradiol, Reglovar, Solestro, and Unistradiol, among others.[15][65][100][111]
^Düsterberg B, Nishino Y (December 1982). "Pharmacokinetic and pharmacological features of oestradiol valerate". Maturitas. 4 (4): 315–324. doi:10.1016/0378-5122(82)90064-0. PMID7169965.
^Stanczyk FZ, Archer DF, Bhavnani BR (June 2013). "Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment". Contraception. 87 (6): 706–727. doi:10.1016/j.contraception.2012.12.011. PMID23375353.
^ abcdefghijklm"NNR: Products Recently Accepted by the A. M. A. Council on Pharmacy and Chemistry". Journal of the American Pharmaceutical Association (Practical Pharmacy Ed.). 10 (11): 692–694. 1949. doi:10.1016/S0095-9561(16)31995-8. ISSN0095-9561.
^ abcdefghOriowo MA, Landgren BM, Stenström B, Diczfalusy E (April 1980). "A comparison of the pharmacokinetic properties of three estradiol esters". Contraception. 21 (4): 415–24. doi:10.1016/S0010-7824(80)80018-7. PMID7389356.
^ abBuschbeck H (1934). "Neue Wege der Hormontherapie in der Gynäkologie" [New ways of hormonal therapy in gynecology]. Deutsche Medizinische Wochenschrift. 60 (11): 389–393. doi:10.1055/s-0028-1129842. ISSN0012-0472. S2CID72668930.
^ abcBiskind MS (1935). "Commercial Glandular Products". Journal of the American Medical Association. 105 (9): 667. doi:10.1001/jama.1935.92760350007009a. ISSN0002-9955. Progynon-B, Schering Corporation: This is crystalline hydroxyestrin benzoate obtained by hydrogenation of theelin and subsequent conversion to the benzoate. [...] Progynon-B is marketed in ampules containing 1 cc. of a sesame oil solution of hydroxyestrin benzoate of either 2,500, 5,000, 10,000 or 50,000 international units.
^ abNovak E (1935). "The Therapeutic Use of Estrogenic Substances". JAMA: The Journal of the American Medical Association. 104 (20): 1815. doi:10.1001/jama.1935.92760200002012. ISSN0098-7484. Progynon B (Schering), in 1 cc. ampules, of 10,000 or 50,000 international units of hydroxyestrin benzoate in sesame oil.
^ abFifková H, Weiss P, Procházka I, Cohen-Kettenis PT, Pfäfflin F, Jarolím L, et al. (4 August 2008). Transsexualita a jiné poruchy pohlavní identity [Transsexuality and other gender identity disorders] (in Czech). Grada Publishing a.s. pp. 95–. ISBN978-80-247-6962-2. Injection of estradiol benzoate is supplied as Agofollin Depot inj. 10 mg, Biotika and as estradiol valerate Neofollin inj., 5 mg, Hoechst-Biotika. Depot estrogen injections are not recommended due to side effects. Possibility "overdose" of the patient is higher (in some individuals receiving doses "the higher the better," and parenteral drug administration may in some instances these cause serious side effects). While misuse of the drug with peroral administration also occurs, the problems are not so extreme.
^American Medical Association. Dept. of Drugs, Council on Drugs (American Medical Association), American Society for Clinical Pharmacology and Therapeutics (1 February 1977). "Estrogens, Progestagens, Oral Contraceptives, and Ovulatory Agents". AMA drug evaluations. Publishing Sciences Group. pp. 540–572. ISBN978-0-88416-175-2. Intramuscular: For replacement therapy, (Estradiol, Estradiol Benzoate) 0.5 to 1.5 mg two or three times weekly; (Estradiol Cypionate) 1 to 5 mg weekly for two or three weeks; (Estradiol Dipropionate) 1 to 5 mg every one to two weeks; (Estradiol Valerate) 10 to 40 mg every one to four weeks.
^Marek J (1 January 2010). Farmakoterapie vnitřních nemocí - 4. zcela přepracované a doplněné vydání. Grada Publishing a.s. pp. 377–. ISBN978-80-247-2639-7. Injection of estrogenic preparations - Injectable preparations are AGOFOLLIN, inj. 5 mg (estradiol dipropionate), AGOFOLLIN DEPOT, inj. 10 mg (estradiol benzoate), and NEOFOLLIN, inj. 5 mg (estradiol valerate). The producer of all these preparations is Biotika. Non-protracted AGOFOLLIN is used only for initiation of treatment, then it is continued with depot injections, which are administered three times: cycle day 4, 11 and 18. At the same time, [progesterone] (AGOLUTIN DEPOT, Biotika, amp. 2 ml / 50 mg, cycle day 18 and 25) is administered. Estrogen injection is not completely physiological - after application, the estrogen plasma concentration increases unnecessarily high and then decreases rapidly.
^Ufer J (1968). "Die therapeutische Anwendung der Gestagene beim Menschen" [Therapeutic Use of Progestagens in Humans]. Die Gestagene [Progestogens]. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology. Springer-Verlag. pp. 1026–1124. doi:10.1007/978-3-642-99941-3_7. ISBN978-3-642-99941-3. C. Dysfunktionelle Uterusblutungen. [...] 1. Depotinjektionen. 1. Originalmethode nach KAUFMANN und OBER. Es wird 1 Amp. mit 200 mg Progesteron und 10 mg Oestradiol-Monobenzoat als Kristallsuspension (Sistocyclin) injiziert [676, 678, 679, 295, 482, 365, 434, 563, 400]. [...] Beispiele. KAUFMANN et al. [485]: 400 mg Progesteron + 20 mg Oestradiolmonobenzoat Kristallsuspension. ELERT [224] U. HERRMANN [363]: 200 mg Progesteron + 10 mg Oestradiolmono benzoat Kristallsuspension.
^Ciba Symposium. Ciba. 1957. CIBA's range of hormone preparations has been increased with the advent of "Sistocyclin", one ampoule of which contains 200 mg progesterone and 10 mg oestradiol monobenzoate in crystalline suspension; it thus meets the requirements—in line with the most recent findings of the KAUFMANN Clinic—of cases marked by deficiency of corpus luteum hormone, e. g. in functional bleeding such as metropathia haemorrhagica.
^Ciba Zeitschrift. 1957. p. 3001. Sistocyclin - a microcrystal suspension containing 200 mg progesterone and 10 mg oestradiol monobenzoate per ampoule - has become particularly useful in the treatment of so-called, functional [...]
^Ciba Symposium: 1953/57:Index. Ciba. 1953. p. 197. Femandren M. C'est le nom des nouvelles ampoules cristallines destinées au traitement associé œs- trogène-androgène. Elles renferment, sous forme de microcristaux, 2,5 mg de mono- benzoate d'œstradiol et 50 mg d'isobutyra- te de testostérone ; elles sont indiquées pour traiter les cas où il convient d'administrer simultanément de l'hormone femelle et de l'hormone mâle et où il importe aussi d'obtenir un effet prolongé, par exemple lors de symptômes d'insuffisance à la ménopause ou après castration. L'effet d'une injection se prolonge pendant 3-6 semaines.
^Martindale W (1958). The Extra Pharmacopoeia. Pharmaceutical Press. p. 960. PROPRIETARY PREPARATIONS CONTAINING OESTRADIOL MONOBENZOATE. Benztrone (Paines & Byrne). Oestradiol monobenzoate, available as an injection in 1-ml. Ampoules of 1, 2, and 5 mg., and in 2-ml. ampoules of 10 mg.; and as Implants of 50 and 100 mg. Dimenformon (Organon). [...] Also available as an Ointment containing 2 mg. per g. in a fatty basis.
^"NNR: Products Recently Accepted by the A. M. A. Council on Pharmacy and Chemistry". Journal of the American Pharmaceutical Association (Practical Pharmacy ed.). 10 (11): 692–694. 1949. doi:10.1016/S0095-9561(16)31995-8. ISSN0095-9561.
^Sahin FK, Koken G, Cosar E, Arioz DT, Degirmenci B, Albayrak R, Acar M (2008). "Effect of Aerodiol administration on ocular arteries in postmenopausal women". Gynecol. Endocrinol. 24 (4): 173–7. doi:10.1080/09513590701807431. PMID18382901. 300 μg 17β-estradiol (Aerodiol®; Servier, Chambrayles-Tours, France) was administered via the nasal route by a gynecologist. This product is unavailable after March 31, 2007 because its manufacturing and marketing are being discontinued.
^Midwinter A (1976). "Contraindications to estrogen therapy and management of the menopausal syndrome in these cases". In Campbell S (ed.). 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. MTP Press Limited. pp. 377–382. doi:10.1007/978-94-011-6165-7_33. ISBN978-94-011-6167-1.
^Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH (February 2001). "Role of cytochrome P450 in estradiol metabolism in vitro". Acta Pharmacol. Sin. 22 (2): 148–54. PMID11741520.
^Bovee TF, Helsdingen RJ, Rietjens IM, Keijer J, Hoogenboom RL (2004). "Rapid yeast estrogen bioassays stably expressing human estrogen receptors alpha and beta, and green fluorescent protein: a comparison of different compounds with both receptor types". J. Steroid Biochem. Mol. Biol. 91 (3): 99–109. doi:10.1016/j.jsbmb.2004.03.118. PMID15276617. S2CID54320898.
^ abcdefghKaiser R (July 1993). "[Gestagen-estrogen combinations in gynecology. On the history, dosage and use of a hormone principle]". Geburtshilfe und Frauenheilkunde. 53 (7): 503–513. doi:10.1055/s-2007-1022924. PMID8370495. S2CID71261744.
^Lauritzen C (1988). "Natürliche und Synthetische Sexualhormone – Biologische Grundlagen und Behandlungsprinzipien" [Natural and Synthetic Sexual Hormones – Biological Basis and Medical Treatment Principles]. In Schneider HP, Lauritzen C, Nieschlag E (eds.). Grundlagen und Klinik der Menschlichen Fortpflanzung [Foundations and Clinic of Human Reproduction] (in German). Walter de Gruyter. pp. 229–306. ISBN978-3110109689. OCLC35483492.
^Ockrim J, Lalani EN, Abel P (October 2006). "Therapy Insight: parenteral estrogen treatment for prostate cancer--a new dawn for an old therapy". Nat Clin Pract Oncol. 3 (10): 552–63. doi:10.1038/ncponc0602. PMID17019433. S2CID6847203.
^Henriksson P, Carlström K, Pousette A, Gunnarsson PO, Johansson CJ, Eriksson B, Altersgård-Brorsson AK, Nordle O, Stege R (July 1999). "Time for revival of estrogens in the treatment of advanced prostatic carcinoma? Pharmacokinetics, and endocrine and clinical effects, of a parenteral estrogen regimen". Prostate. 40 (2): 76–82. doi:10.1002/(sici)1097-0045(19990701)40:2<76::aid-pros2>3.0.co;2-q. PMID10386467. S2CID12240276.
^Vizziello G, D'Amato G, Trentadue R, Fanizza G (1993). "[Estradiol benzoate test in the study of pituitary block induced by triptorelin]". Minerva Ginecol (in Italian). 45 (4): 185–9. PMID8506068.
^ abKaiser R (September 1961). "[Estrogen excretion during the cycle and after injection of estradiol esters. A contribution to therapy with depot estrogens]" [Estrogen excretion during the cycle and after injection of estradiol esters. A contribution to therapy with depot estrogens]. Geburtshilfe und Frauenheilkunde (in German). 21: 868–878. PMID13750804.
^ abKaiser R (1962). "Über die Oestrogenausscheidung nach Injektion von Oestradiolestern" [Estrogen excretion after injection of estradiol esters]. Gewebs-und Neurohormone: Physiologie des Melanophorenhormons [Tissue and Neurohormones: Physiology of the Melanophore Hormone]. Symposion der Deutschen Gesellschaft für Endokrinologie (in German). Springer, Berlin, Heidelberg. pp. 227–232. doi:10.1007/978-3-642-86860-3_24. ISBN978-3-540-02909-0.
^ abcShaw RW, Butt WR, London DR (May 1975). "The effect of oestrogen pretreatment on subsequent response to luteinizing hormone releasing hormone in normal women". Clin. Endocrinol. (Oxf). 4 (3): 297–304. doi:10.1111/j.1365-2265.1975.tb01537.x. PMID1097136. S2CID12139717.
^ abcLeyendecker G, Geppert G, Nocke W, Ufer J (May 1975). "Untersuchungen zur Pharmakokinetik von Östradiol-17β, Östradiol-benzoat, Östradiol-Valerianat un Östradiol-Undezylat bei der Frau: Der Verlauf der Konzentration von Östradiol-17β, Östron, LH und FSH im Serum" [Estradiol 17β, estrone, LH and FSH in serum after administration of estradiol 17β, estradiol benzoate, estradiol valeriate and estradiol undecylate in the female]. Geburtshilfe Frauenheilkd (in German). 35 (5): 370–374. ISSN0016-5751. PMID1150068.
^von Wattenwyl H (1944). "Über eine neue Anwendungsart oestrogener Substanzen" [A new type of application of estrogenic substances]. Schweiz. Med. Wochenschr. (in German). 74: 159–161.
^Ferin J (January 1952). "Relative duration of action of natural and synthetic estrogens administered parenterally in women with estrogen deficiency". The Journal of Clinical Endocrinology and Metabolism. 12 (1): 28–35. doi:10.1210/jcem-12-1-28. PMID14907837.
^Ober KG, Klein I, Weber M (1954). "[The problem of progesterone therapy; experimental studies on the Hooker-Forbes test and clinical observations on crystalline suspensions]" [On the question of progesterone treatment: experimental studies with the Hooker-Forbes test and clinical observations with crystal suspensions]. Archiv für Gynäkologie. 184 (5): 543–616. doi:10.1007/BF00976991. PMID13198154. S2CID42832785.
^Field-Richards S (April 1955). "A preliminary series of cases of uterine hypoplasia treated by local injection of an oestrogenic emulsion". The Journal of Obstetrics and Gynaecology of the British Empire. 62 (2): 205–213. doi:10.1111/j.1471-0528.1955.tb14121.x. PMID14368390. S2CID41256797. Oestradiol monobenzoate or oestradiol diproprionate are slowly absorbed from oily solution after intramuscular injection and for this purpose are to be preferred to the unesterified form. As an even slower absorption of oestradiol monobenzoate can be obtained from an aqueous emulsion of this hormone (Lens, Overbeek and Polderman, 1949). Such a preparation for parenteral use was made available for this experiment by Messrs. Organon Laboratories Limited.
^ abLens J, Overbeek GA, Polderman J (1949). "The effect of sex hormones in some organic solvents; emulsified in water". Acta Endocrinologica. 2 (4): 396–404. doi:10.1530/acta.0.0020396. PMID18140399.
^Dorfman RI (5 December 2016). Steroidal Activity in Experimental Animals and Man. Elsevier Science. pp. 40–. ISBN978-1-4832-7299-3. Ferin (1952) also studied duration of action in women with estrogen deficiency by recording the days of freedom from hot flushes. He rates estradiol-3-benzoate, estradiol-3-furoate, estradiol dipropionate, estradiol-17-caprylate, estradiol-3-benzoate-17-caprylate in oil, and finally estradiol-3-benzoate in emulsion or as microcrystals in that order of duration of action. After 10 mg. of each of the above preparations, a woman would typically remain free of symptoms for 10 days. This could, however, be as much as 50 days.
^Herrmann U (1958). "Abhängigkeit der durch Oestrogen- und Progesteron-Kristalle induzierten Abbruchblutung von der Korngröße". Gynecologic and Obstetric Investigation. 146 (4): 318–323. doi:10.1159/000306607. ISSN1423-002X.
^Butenandt A, Störmer I (1932). "Über isomere Follikelhormone. Untersuchungen über das weibliche Sexualhormon, 7. Mitteilung" [About isomeric follicle hormones. Studies on the female sex hormone, 7th communication.]. Hoppe-Seyler's Zeitschrift für physiologische Chemie. 208 (4): 129–148. doi:10.1515/bchm2.1932.208.4.129. ISSN0018-4888.
^Toppozada M, Goldsmith A, eds. (1983). Long-acting Contraception (Report). Program for Applied Research on Fertility Regulation, Northwestern University. pp. 94–95. Archived from the original on 24 March 2019.
Lambang kota Eichenbühl adalah kotamadya di Distrik Miltenberg, Regierungsbezirk Unterfranken, Bayern, Jerman. Geografi Eichenbühl terletak di Bayerischer Untermain, sekitar 5 km di timur Miltenberg di Geo-Naturpark Bergstraße-Odenwald. Terdapat sejumlah ortsteil di Eichenbühl, seperti Guggenberg, Heppdiel, Pfohlbach, Riedern dan Windischbuchen. Wikimedia Commons memiliki media mengenai Eichenbühl. lbsKota dan kotamadya di MiltenbergAltenbuch | Amorbach | Bürgstadt |...
Arungan Rawney yang terletak di salah satu anak Sungai Lyne di Cumbria, Inggris Arungan[1] (Inggris: fordcode: en is deprecated ) adalah tempat dangkal di sungai yang dapat dilintasi dengan berjalan kaki atau bahkan menggunakan kendaraan.[2] Arungan bisa muncul secara alami atau dibangun oleh manusia. Arungan merupakan sarana untuk melintasi sungai yang lebih murah daripada jembatan, tetapi arungan tidak dapat dilintasi ketika hujan deras atau pada saat permukaan air sungai me...
Artikel ini sebatang kara, artinya tidak ada artikel lain yang memiliki pranala balik ke halaman ini.Bantulah menambah pranala ke artikel ini dari artikel yang berhubungan atau coba peralatan pencari pranala.Tag ini diberikan pada Januari 2023. Acanthosaura bintangensis Status konservasiKekurangan dataIUCN99927868 TaksonomiKerajaanAnimaliaFilumChordataKelasReptiliaOrdoSquamataFamiliAgamidaeGenusAcanthosauraSpesiesAcanthosaura bintangensis lbs Acanthosaura bintangensis, agamid bertanduk Gunung...
هذه المقالة يتيمة إذ تصل إليها مقالات أخرى قليلة جدًا. فضلًا، ساعد بإضافة وصلة إليها في مقالات متعلقة بها. (مارس 2021) كونغرس نقابات العمال في تنزانيا البلد تنزانيا تاريخ التأسيس 2000 الموقع الرسمي الموقع الرسمي تعديل مصدري - تعديل كونغرس نقابات العمال في تنزانيا �...
Disambiguazione – Se stai cercando l'omonimo monte situato sulla superficie del pianeta Venere, vedi Maat Mons. Disambiguazione – Se stai cercando il grado militare tedesco, vedi Maat (grado militare). Maat Maat (Giustizia) era l'antico concetto[1] egizio dell'equilibrio, dell'ordine, dell'armonia, della verità, della legge e regola, della moralità e della giustizia[2]. Era inoltre personificata come una dea antropomorfa, con una piuma in capo[2], responsabile d...
BermudaA map of the Bermuda IslandsAdministrationUnited Kingdom Map all coordinates using OpenStreetMap Download coordinates as: KML GPX (all coordinates) GPX (primary coordinates) GPX (secondary coordinates) Bermuda is an archipelago consisting of 181 islands. List of islands Name Image Coordinates Parish Note Agar's Island 32°17′38″N 64°48′33″W / 32.29389°N 64.80917°W / 32.29389; -64.80917 (Agar's Island) Pembroke In Great Sound. Was owned by bil...
Penampang lintang batang, teras kayu adalah lingkaran yang berwarna coklat gelap. Teras kayu, hati kayu atau duramen adalah bagian dari jaringan kayu pada batang yang terdalam, berisi sel-sel yang sangat terlignifikasi. Bagian ini berada di bagian dalam dari jaringan kayu lain yang lebih luar, alburnum. Teras kayu sering mudah dibedakan dari alburnum karena warnanya yang lebih gelap. Di dalam teras kayu terletak empulur.
The QuintURLhttps://www.thequint.com/ dan http://thequint.com TipeBeritaLangueInggris & HindiPemilikGaurav Mercantiles Ltd Raghav Bahl & Ritu Kapur (66.42%) Haldiram's Pvt Ltd (17-18%) Elara Capital Ltd (10%) Mohan Lal Jain (4.99%) Service entry2015Peringkat Alexa 8,552 (Global, Mei 2020)[1] 653 (India, Mei 2020)[1] The Quint adalah sebuah situs web media India berbahasa Inggris dan Hindi dan tersedia di beberapa platfrom medsos seperti instagram,youtube dan di google ...
Booker T. and the M.G.'s Le groupe en 2002Informations générales Pays d'origine États-Unis Genre musical Soul Années actives 1961-19711973-19771994-présent Labels Stax Records Composition du groupe Membres Booker T. Jones Steve CropperSteve Potts Anciens membres Al Jackson, Jr. (†)Lewie Steinberg (†)Donald Duck Dunn (†)Bobby ManuelCarson WhitsettWillie HallAnton FigSteve Jordan modifier Booker T. and the M.G.'s est un groupe américain de musique soul instrumental, connaissant son...
Khuzdul Creato daJ.R.R. Tolkien nel 1940 Contestoil mondo immaginario di Arda nel romanzo Il Signore degli Anelli Altre informazioniScritturaCirth, alfabeto latino TassonomiaFilogenesiLingue artificiali Lingue artistiche Khuzdul Codici di classificazioneISO 639-2art Estratto in lingua TraslitterazioneBalin / Fundinul / Uzbad Khazad-dûmu Balin, figlio di Fundin, signore di Khazad-dûm. Manuale Iscrizioni in Khuzdul sulla tomba di Balin, signore di Moria (ART) «Baruk Khazâd! ...
SNG DRAMAUbicazioneStato Slovenia LocalitàLubiana Indirizzon. 18 di via Erjavec RealizzazioneInaugurazione24 ottobre 1867 Sito ufficiale Modifica dati su Wikidata · Manuale Il Teatro drammatico nazionale di Lubiana (o Teatro Drammatico Nazionale sloveno di Lubiana), è il teatro nazionale della Slovenia, sito a Lubiana, ben conosciuto per il suo repertorio tradizionale, che comprende opere europee e slovene drammatiche classiche e opere contemporanee scelte, non commerciali. La su...
此條目需要补充更多来源。 (2021年7月4日)请协助補充多方面可靠来源以改善这篇条目，无法查证的内容可能會因為异议提出而被移除。致使用者：请搜索一下条目的标题（来源搜索：美国众议院 — 网页、新闻、书籍、学术、图像），以检查网络上是否存在该主题的更多可靠来源（判定指引）。 美國眾議院 United States House of Representatives第118届美国国会众议院徽章 众议院旗...
Kimberly BirrellBirrell di kualifikasi Kejuaraan Wimbledon 2019Kebangsaan AustraliaTempat tinggalGold Coast, AustraliaLahir29 April 1998 (umur 26)Düsseldorf, JermanTinggi170 cm (5 ft 7 in)Memulai pro2014Tipe pemainKanan (backhand dua tangan)Total hadiahUS$ 665,139TunggalRekor (M–K)145–126 (53.51%)Gelar4 ITFPeringkat tertinggiNo. 115 (6 Maret 2023)Peringkat saat iniNo. 115 (6 Maret 2023)Hasil terbaik di Grand Slam (tunggal)Australia TerbukaR3 (2019)Prancis Te...
Indian social activist and advocate of Dravidian movement For other uses, see Periyar (disambiguation). PeriyarPortrait of Periyar on a postage stampPresident of Dravidar KazhagamIn office27 August 1944 – 24 December 1973Preceded byPosition establishedSucceeded byAnnai E. V. R. ManiammaiHead of the Justice PartyIn office1939 – 27 August 1944Inaugural HolderC. Natesa MudaliarPreceded byRamakrishna Ranga Rao of BobbiliSucceeded byP. T. Rajan Personal detailsBorn(1879-09-17...
Zulkarnain Adinegara Kakorpolairud Baharkam Polri ke-2Masa jabatan20 Juni 2019 – 21 Oktober 2019PendahuluChairul Noor AlamsyahPenggantiLotharia LatifKepala Kepolisian Daerah Sumatera SelatanMasa jabatan25 Agustus 2017 – 20 Juni 2019PendahuluAgung Budi MaryotoPenggantiFirli BahuriKepala Kepolisian Daerah RiauMasa jabatan23 September 2016 – 25 Agustus 2017PendahuluSupriyantoPenggantiNandangKepala Kepolisian Daerah Maluku UtaraMasa jabatan3 September 2015...
State government in Pakistani-administered Kashmir This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Government of Gilgit-Baltistan – news · newspapers · books · scholar · JSTOR (January 2024) (Learn how and when to remove this message) Government of Gilgit-BaltistanSeat of government GilgitLegislatureAss...
![Estradiol levels after single intramuscular injections of 0.5, 1.5, or 2.5 mg estradiol benzoate in oil in 5 premenopausal women each.[77] Assays were performed using radioimmunoassay.[77] Source was Shaw et al. (1975).[77]](File:Estradiol_levels_after_single_intramuscular_injections_of_different_doses_of_estradiol_benzoate_in_premenopausal_women.png)
![Estradiol levels after single intramuscular injections of 5 mg of different estradiol esters in oil in about 10 premenopausal women each.[9] Assays were performed using radioimmunoassay with chromatographic separation.[9] Source was Oriowo et al. (1980).[9]](File:Estradiol_levels_after_a_single_5_mg_intramuscular_injection_of_estradiol_esters.png)
![Estradiol levels after a short intravenous infusion of 20 mg estradiol in aqueous solution or an intramuscular injection of equimolar doses of estradiol esters in oil solution in postmenopausal women.[78][79] Assays were performed using RIA with CS.[78][79] Source was Geppert (1975).[78][79]](File:Estradiol_levels_after_injections_of_estradiol,_estradiol_benzoate,_estradiol_valerate,_and_estradiol_undecylate_in_women.png)
![Simplified curves of estradiol levels after injection of different estradiol esters in women.[80] Source was Garza-Flores (1994).[80]](File:Idealized_curves_of_estradiol_levels_after_injection_of_different_estradiol_esters_in_women.png)
![Vaginal cornification with a single intramuscular injection of different estradiol esters in oil solution in women.[25] Source was Schwartz & Soule (1955).[25]](File:Vaginal_cornification_with_a_single_intramuscular_injection_of_different_estradiol_esters_in_women.png)
