Estradiol dipropionate

Last updated
Estradiol dipropionate
Estradiol dipropionate.svg
Estradiol dipropionate molecule ball.png
Clinical data
Trade names Agofollin, Di-Ovocylin, Progynon DP, others
Other namesEDP; Estradiol dipropionate; Estradiol 3,17β-dipropionate; Estra-1,3,5(10)-triene-3,17β-diol 3,17β-dipropanoate
Routes of
administration 		Intramuscular injection
Drug class Estrogen; Estrogen ester
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability IM: High [1]
Protein binding Estradiol: ~98% (to albumin and SHBG) [2] [3]
Metabolism Cleavage via esterases in the liver, blood, and tissues [4] [5]
Metabolites Estradiol, benzoic acid, and metabolites of estradiol [4] [5]
Elimination half-life Unknown
Duration of action IM (5 mg): 5–8 days [6] [7]
Excretion Urine
Identifiers
  • [(8R,9S,13S,14S,17S)-13-methyl-3-propanoyloxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] propanoate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.003.660 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C24H32O4
Molar mass 384.516 g·mol−1
3D model (JSmol)
  • O=C(Oc1cc3c(cc1)[C@H]2CC[C@@]4([C@@H](OC(=O)CC)CC[C@H]4[C@@H]2CC3)C)CC
  • InChI=1S/C24H32O4/c1-4-22(25)27-16-7-9-17-15(14-16)6-8-19-18(17)12-13-24(3)20(19)10-11-21(24)28-23(26)5-2/h7,9,14,18-21H,4-6,8,10-13H2,1-3H3/t18-,19-,20+,21+,24+/m1/s1
  • Key:JQIYNMYZKRGDFK-RUFWAXPRSA-N

Estradiol dipropionate (EDP), sold under the brand names Agofollin, Di-Ovocylin, and Progynon DP among others, is an estrogen medication which has been used in hormone therapy for menopausal symptoms and low estrogen levels in women and in the treatment of gynecological disorders. [8] [9] [10] [11] [12] [13] It has also been used in feminizing hormone therapy for transgender women and in the treatment of prostate cancer in men. [14] [8] Although widely used in the past, estradiol dipropionate has largely been discontinued and is mostly no longer available today. [15] [13] [11] It appears to remain in use only in Japan, Macedonia, and Australia. [13] Estradiol dipropionate is given by injection into muscle at intervals ranging from once or twice a week to once every week and a half to two weeks. [8] [16] [14]

Contents

Side effects of estradiol dipropionate include breast tenderness, breast enlargement, nausea, headache, and fluid retention. [17] Estradiol dipropionate is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol. [5] [4] It is an estrogen ester and a prodrug of estradiol in the body. [4] [5] Because of this, it is considered to be a natural and bioidentical form of estrogen. [4]

Estradiol dipropionate was patented in 1937 [18] and was introduced for medical use by 1940. [19] [20] It was one of the earliest estradiol esters to be used. [8] Along with estradiol benzoate, estradiol dipropionate was among the most widely used esters of estradiol for many years following its introduction. [15]

Medical uses

The medical uses of estradiol dipropionate are the same as those of estradiol and other estrogens. [8] [9] Estradiol dipropionate is used in hormone therapy for the treatment of menopausal symptoms such as hot flashes and vaginal atrophy and in the treatment of hypoestrogenism and delayed puberty due to hypogonadism or other causes in women. [8] [9] It is also used in feminizing hormone therapy for transgender women. [14] Aside from hormone therapy, estradiol dipropionate is used in the treatment of gynecological disorders such as menstrual disorders, dysfunctional uterine bleeding, and breast engorgement. [8] [9] In addition, it is used as a form of high-dose estrogen therapy in the palliative treatment of prostate cancer in men. [8]

Estradiol dipropionate has typically been used at a dosage of 1 to 5 mg once or twice per week by intramuscular injection for relevant indications. [8] [16] It has been used in the treatment of menopausal symptoms at a dosage of 1 to 5 mg initially for two to three injections and 1 to 2.5 mg for maintenance once every 10 to 14 days, and in the treatment of hypoestrogenism and delayed puberty at a dosage of 2.5 to 5 mg once per week. [8] [21] As a component of feminizing hormone therapy for transgender women, estradiol dipropionate has been used at dosages of 2 to 10 mg once per week or 5 to 20 mg once every 2 weeks. [14] In the treatment of prostate cancer, estradiol dipropionate has been used at a dosage of 5 mg once per week. [8]

Available forms

Estradiol dipropionate was previously available by itself as an oil solution for intramuscular injection provided as vials and ampoules at concentrations of 0.1, 0.2, 0.5, 1, 2.5, and 5 mg/mL. [8] [22] [23] [24] [25] The medication has largely been discontinued, with most of these formulations no longer being available. [11] [13] Estradiol dipropionate remains available at a concentration of 1 mg/mL in combination with 50 mg/mL hydroxyprogesterone caproate under the brand name EP Hormone Depot (Teikoku Zoki Pharmaceutical Company) in Japan. [26] [27] [28] [29] [30] [31] [32]

Contraindications

Contraindications of estrogens include coagulation problems, cardiovascular diseases, liver disease, and certain hormone-sensitive cancers such as breast cancer and endometrial cancer, among others. [33] [34] [35] [36]

Side effects

The side effects of estradiol dipropionate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma. [17]

Overdose

Symptoms of estrogen overdosage may include nausea, vomiting, bloating, increased weight, water retention, breast tenderness, vaginal discharge, heavy legs, and leg cramps. [33] These side effects can be diminished by reducing the estrogen dosage. [33]

Interactions

Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels. [37]

Pharmacology

Estradiol, the active form of estradiol dipropionate. Estradiol.svg
Estradiol, the active form of estradiol dipropionate.

Pharmacodynamics

Estradiol dipropionate 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 dipropionate is of about 41% higher molecular weight than estradiol due to the presence of its C3 and C17β propionate esters. [10] [11] Because estradiol dipropionate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen. [4]

Potencies and durations of natural estrogens by intramuscular injection
EstrogenFormDose (mg)Duration by dose (mg)
EPDCICD
Estradiol Aq. soln. ?–<1 d
Oil soln.40–60–1–2 ≈ 1–2 d
Aq. susp. ?3.50.5–2 ≈ 2–7 d; 3.5 ≈ >5 d
Microsph. ?–1 ≈ 30 d
Estradiol benzoate Oil soln.25–35–1.66 ≈ 2–3 d; 5 ≈ 3–6 d
Aq. susp.20–10 ≈ 16–21 d
Emulsion ?–10 ≈ 14–21 d
Estradiol dipropionateOil soln.25–30–5 ≈ 5–8 d
Estradiol valerate Oil soln.20–3055 ≈ 7–8 d; 10 ≈ 10–14 d;
40 ≈ 14–21 d; 100 ≈ 21–28 d
Estradiol benz. butyrate Oil soln. ?1010 ≈ 21 d
Estradiol cypionate Oil soln.20–30–5 ≈ 11–14 d
Aq. susp. ?55 ≈ 14–24 d
Estradiol enanthate Oil soln. ?5–1010 ≈ 20–30 d
Estradiol dienanthate Oil soln. ?–7.5 ≈ >40 d
Estradiol undecylate Oil soln. ?–10–20 ≈ 40–60 d;
25–50 ≈ 60–120 d
Polyestradiol phosphate Aq. soln.40–60–40 ≈ 30 d; 80 ≈ 60 d;
160 ≈ 120 d
Estrone Oil soln. ?–1–2 ≈ 2–3 d
Aq. susp. ?–0.1–2 ≈ 2–7 d
Estriol Oil soln. ?–1–2 ≈ 1–4 d
Polyestriol phosphate Aq. soln. ?–50 ≈ 30 d; 80 ≈ 60 d
Notes and sources
Notes: All aqueous suspensions are of microcrystalline particle size. Estradiol production during the menstrual cycle is 30–640 µg/d (6.4–8.6 mg total per month or cycle). The vaginal epithelium maturation dosage of estradiol benzoate or estradiol valerate has been reported as 5 to 7 mg/week. An effective ovulation-inhibiting dose of estradiol undecylate is 20–30 mg/month. Sources: See template.

Pharmacokinetics

Compared to estradiol benzoate, a related estradiol ester, estradiol dipropionate has enhanced and prolonged effects. [38] [16] Whereas the duration of action of estradiol benzoate is said to be 2 to 3 days, the duration of estradiol dipropionate has been said to be 1 to 2 weeks. [39] However, newer estradiol esters have longer durations than either estradiol benzoate or estradiol dipropionate; the duration of estradiol valerate has been said to be 1 to 3 weeks, and the duration of estradiol cypionate has been said to be 3 to 4 weeks. [39] [16] A single intramuscular injection of 5 mg estradiol dipropionate has a duration of about 5 to 8 days. [6] [7]

A single intramuscular injection of 50 μg/kg estradiol dipropionate in oil in 15 pubertal girls (about 1 mg for a 50-kg (110-lb) girl) was found to produce peak estradiol levels of about 215 pg/mL after 1.5 days. [40] Estradiol levels declined to about 90 pg/mL after 4 days. [40]

Chemistry

Estradiol dipropionate, also known as estradiol 3,17β-dipropionate, is a synthetic estrane steroid and a derivative of estradiol. [10] [11] It is an estrogen ester; specifically, it is the C3,17β dipropionate ester of estradiol. [10] [11]

The experimental octanol/water partition coefficient (logP) of estradiol dipropionate is 4.9. [42]

Structural properties of selected estradiol esters
EstrogenStructureEster(s)Relative
mol. weight		Relative
E2 contentb		log Pc
Position(s)Moiet(ies)TypeLengtha
Estradiol
Estradiol.svg
––––1.001.004.0
Estradiol acetate
Estradiol 3-acetate.svg
C3 Ethanoic acid Straight-chain fatty acid21.150.874.2
Estradiol benzoate
Estradiol benzoate.svg
C3 Benzoic acid Aromatic fatty acid– (~4–5)1.380.724.7
Estradiol dipropionate
Estradiol dipropionate.svg
C3, C17β Propanoic acid (×2)Straight-chain fatty acid3 (×2)1.410.714.9
Estradiol valerate
Estradiol valerate.svg
C17β Pentanoic acid Straight-chain fatty acid51.310.765.6–6.3
Estradiol benzoate butyrate
Estradiol butyrate benzoate.svg
C3, C17β Benzoic acid, butyric acid Mixed fatty acid– (~6, 2)1.640.616.3
Estradiol cypionate
Estradiol 17 beta-cypionate.svg
C17β Cyclopentylpropanoic acid Cyclic fatty acid– (~6)1.460.696.9
Estradiol enanthate
Estradiol enanthate.png
C17β Heptanoic acid Straight-chain fatty acid71.410.716.7–7.3
Estradiol dienanthate
Estradiol dienanthate.svg
C3, C17β Heptanoic acid (×2)Straight-chain fatty acid7 (×2)1.820.558.1–10.4
Estradiol undecylate
Estradiol undecylate.svg
C17β Undecanoic acid Straight-chain fatty acid111.620.629.2–9.8
Estradiol stearate
Estradiol stearate structure.svg
C17β Octadecanoic acid Straight-chain fatty acid181.980.5112.2–12.4
Estradiol distearate
Estradiol distearate.svg
C3, C17β Octadecanoic acid (×2)Straight-chain fatty acid18 (×2)2.960.3420.2
Estradiol sulfate
Estradiol sulfate.svg
C3 Sulfuric acid Water-soluble conjugate–1.290.770.3–3.8
Estradiol glucuronide
Estradiol sulfate.svg
C17β Glucuronic acid Water-soluble conjugate–1.650.612.1–2.7
Estramustine phosphate d
Estramustine phosphate.svg
C3, C17β Normustine, phosphoric acid Water-soluble conjugate–1.910.522.9–5.0
Polyestradiol phosphate e
Polyestradiol phosphate.svg
C3–C17β Phosphoric acid Water-soluble conjugate–1.23f0.81f2.9g
Footnotes:a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic or cyclic fatty acids. b = Relative estradiol content by weight (i.e., relative estrogenic exposure). c = Experimental or predicted octanol/water partition coefficient (i.e., lipophilicity/hydrophobicity). Retrieved from PubChem, ChemSpider, and DrugBank. d = Also known as estradiol normustine phosphate. e = Polymer of estradiol phosphate (~13 repeat units). f = Relative molecular weight or estradiol content per repeat unit. g = log P of repeat unit (i.e., estradiol phosphate). Sources: See individual articles.

History

Estradiol dipropionate was first synthesized and patented in 1937. [43] [18] It was assessed in clinical studies by 1939 and was introduced by Ciba as an oil solution for use by intramuscular injection under the brand name Di-Ovocylin by the same year. [43] [38] [19] Other formulations such as Ovocyclin P by Ciba, Progynon DP by Schering and Dimenformon Dipropionate by Roche-Organon were also marketed by the early 1940s. [44] [45] [20] [46] Later in the 1940s the brand name Di-Ovocylin was changed by Ciba to Ovocylin Dipropionate. [22] Along with estradiol benzoate, which was introduced in 1933, [47] estradiol dipropionate was one of the first estradiol esters to be introduced for medical use. [48] [45] Prior to the development and introduction of longer-acting estradiol esters like estradiol valerate and estradiol cypionate in the 1950s, estradiol dipropionate and estradiol benzoate were the most widely used estradiol esters. [15] [49]

Society and culture

Generic names

Estradiol dipropionate is the generic name of the drug and its INNM, BANM, and JAN. [10] [11] [12] [13]

Brand names

Estradiol dipropionate has been marketed under a variety of brand names, including Agofollin, Akrofolline, Dihidrofolina "Kével", Dimenformon, Dimenformon Dipropionate, Diovocylin, Di-Ovocylin, Diprostron, Diprovex, Endofollicolina D.P., EP Hormone Depot (in combination with hydroxyprogesterone caproate), Estroici, Estronex, Follicyclin, Follicyclin P, Follikelmon Depot, Horiken-Depot, Nacyclyl, Oestradiol Galenika, Oestradiol Streuli, Orofollina, Ovacrin, Ovahormon Depot, Ovocylin, Ovocylin Dipropionate, Ovocylin P, and Progynon DP, among others. [50] [10] [11] [12] [51] [52] [13] Agofollin was an oil solution of estradiol dipropionate that was previously marketed in the Czech Republic and Slovakia. [53]

Availability

Estradiol dipropionate has been discontinued in most countries, but remains available in Japan and Macedonia alone under the brand names Ovahormon and Oestradiol Galenika and/or in combination with hydroxyprogesterone caproate under the brand name EP Hormone Depot. [11] [13] It is also marketed for use in veterinary medicine in combination with hydroxyprogesterone caproate and nandrolone decanoate under the brand name Reepair in Australia. [13]

See also

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References

  1. ↑ 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. PMID   7169965.
  2. ↑ 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. PMID   23375353.
  3. ↑ Gupta MK, Chia SY (2007). "Ovarian hormones: structure, biosynthesis, function, mechanism of action, and laboratory diagnosis". In Falcone T, Hurd WW (eds.). Clinical Reproductive Medicine and Surgery. Elsevier Health Sciences. pp. 22, 362, 388. ISBN   978-0-323-03309-1.
  4. 1 2 3 4 5 6 7 8 Oettel M, Schillinger E, Kuhnz W, Blode H, Zimmermann H (6 December 2012). "Pharmacokinetics of exogenous natural and synthetic estrogens and antiestrogens". In Oettel M, Schillinger E (eds.). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. p. 261. ISBN   978-3-642-60107-1. Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens.
  5. 1 2 3 4 5 6 Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID   16112947. S2CID   24616324.
  6. 1 2 Knörr K, Knörr-Gärtner H, Beller FK, Lauritzen C (8 March 2013). Lehrbuch der Geburtshilfe und Gynäkologie: Physiologie und Pathologie der Reproduktion. Springer-Verlag. pp. 508–. ISBN   978-3-662-00526-2.
  7. 1 2 Knörr K, Beller FK, Lauritzen C (17 April 2013). Lehrbuch der Gynäkologie. Springer-Verlag. pp. 212–213. ISBN   978-3-662-00942-0.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 "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. ISSN   0095-9561.
  9. 1 2 3 4 Swyer GI (April 1959). "The oestrogens". British Medical Journal. 1 (5128): 1029–1031. doi:10.1136/bmj.1.5128.1029. PMC   1993181 . PMID   13638626.
  10. 1 2 3 4 5 6 Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 898–. ISBN   978-1-4757-2085-3.
  11. 1 2 3 4 5 6 7 8 9 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 406–. ISBN   978-3-88763-075-1.
  12. 1 2 3 Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 206–. ISBN   978-94-011-4439-1.
  13. 1 2 3 4 5 6 7 8 "Estradiol: Uses, Dosage & Side Effects". Drugs.com.
  14. 1 2 3 4 Nakatsuka M (May 2010). "Endocrine treatment of transsexuals: assessment of cardiovascular risk factors". Expert Review of Endocrinology & Metabolism. 5 (3): 319–322. doi: 10.1586/eem.10.18 . PMID   30861686. S2CID   73253356.
  15. 1 2 3 Schwartz MM, Soule SD (July 1955). "Estradiol 17-beta-cyclopentylpropionate, a longacting estrogen". American Journal of Obstetrics and Gynecology. 70 (1): 44–50. doi:10.1016/0002-9378(55)90286-6. PMID   14388061.
  16. 1 2 3 4 Huhnstock KH, Kutscha W, Dehmel H (12 March 2013). Diagnose und Therapie in der Praxis. Springer-Verlag. pp. 1053–. ISBN   978-3-642-68385-5.
  17. 1 2 McIver B, Tebben PJ, Shas P (23 September 2010). "Endocrinology". In Ghosh AK (ed.). Mayo Clinic Internal Medicine Board Review. OUP USA. pp. 222–. ISBN   978-0-19-975569-1.
  18. 1 2 USpatent 2233025,Miescher K, Scholz C,"Estradiol-17-monoesters",published 1941-02-25, assigned to Ciba Pharmaceutical Products, Inc.
  19. 1 2 Escamilla RF, Lisserf H (1940). "Induction of menarche and development of secondary sexual characteristics in a woman aged 34 by injections of estradiol dipropionate". Endocrinology. 27 (1): 153. doi:10.1210/endo-27-1-153. ISSN   0013-7227. The estradiol dipropionate used in this case was furnished by the Ciba Co. Their trade name for this product is Di-Ovocylin.
  20. 1 2 Shorr E (1940). "Effect of Concomitant Administration of Estroens and Proesterone on Vainal Smear in Man". Experimental Biology and Medicine. 43 (3): 501–506. doi:10.3181/00379727-43-11244. ISSN   1535-3702. S2CID   75787837. Grateful acknowledgment is made to Dr. Erwin Schwenk of the Schering Corporation for the estradiol benzoate (Progynon B), estradiol dipropionate (Progynon DP), progesterone (Proluton), and pregneninolone (Pranone) used in these experiments;
  21. ↑ 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. ISBN   978-0-88416-175-2. 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.
  22. 1 2 "New Prescription Products". Journal of the American Pharmaceutical Association (Practical Pharmacy Ed.). 10 (4): 198–206. 1949. doi:10.1016/S0095-9561(16)31795-9. ISSN   0095-9561.
  23. ↑ Indian Pharmaceutical Guide. Pamposh Publications. 1968.
  24. ↑ Modell W (21 November 2013). Drugs in Current Use 1958. Springer. pp. 51–. ISBN   978-3-662-40303-7.
  25. ↑ Hospital Formulary and Compendium of Useful Information. University of California Press. 1952. pp. 49–. GGKEY:2UAAZRZ5LN0.
  26. ↑ Kawamura I, Mizota T, Lacey E, Tanaka Y, Manda T, Shimomura K, Kohsaka M (September 1993). "The estrogenic and antiestrogenic activities of droloxifene in human breast cancers". Japanese Journal of Pharmacology. 63 (1): 27–34. doi: 10.1254/jjp.63.27 . PMID   8271528.
  27. ↑ Asanuma F, Yamada Y, Kawamura E, Lee K, Kobayashi H, Yamada T, et al. (1998). "Antitumor activity of paclitaxel and epirubicin in human breast carcinoma, R-27". Folia Microbiologica. 43 (5): 473–474. doi:10.1007/BF02820793. PMID   9821299. S2CID   22732235.
  28. ↑ Noguchi M, Tajiri K, Taniya T, Kumaki T, Ashikari A, Miyazaki I (1990). "Influence of hormones on proliferation of ER-positive cells and ER-negative cells of human breast cancer (MCF-7)". Oncology. 47 (1): 19–24. doi:10.1159/000226779. PMID   2137212.
  29. ↑ Kubota T, Oka S, Utsumi T, Inoue S, Kuzuoka M, Suto A, et al. (July 1989). "Human breast carcinoma (ZR-75-1) serially transplanted into nude mice--with reference to estradiol dependency and sensitivity to tamoxifen". The Japanese Journal of Surgery. 19 (4): 446–451. doi:10.1007/BF02471626. PMID   2810959. S2CID   23267652.
  30. ↑ Ueda H, Nakajima H, Hori Y, Fujita T, Nishimura M, Goto T, Okuhara M (March 1994). "FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity". The Journal of Antibiotics. 47 (3): 301–310. doi: 10.7164/antibiotics.47.301 . PMID   7513682.
  31. ↑ Hori Y, Abe Y, Nishimura M, Goto T, Okuhara M, Kohsaka M (July 1993). "R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. III. Pharmacological properties and antitumor activities". The Journal of Antibiotics. 46 (7): 1069–1075. doi: 10.7164/antibiotics.46.1055 . PMID   8360101.
  32. ↑ Noguchi M, Koyasaki N, Miyazaki I, Mizukami Y (November 1991). "Effects of hormones on tumor growth and immunoreactive insulin-like growth factor-1 of estrogen receptor-positive human breast cancer (MCF-7) transplanted in nude mice". Japanese Journal of Cancer Research. 82 (11): 1199–1202. doi:10.1111/j.1349-7006.1991.tb01780.x. PMC   5918318 . PMID   1752778.
  33. 1 2 3 Lauritzen C (September 1990). "Clinical use of oestrogens and progestogens". Maturitas. 12 (3): 199–214. doi:10.1016/0378-5122(90)90004-P. PMID   2215269.
  34. ↑ Lauritzen C (22 June 2005). "Practice of Hormone Substitution". In Lauritzen C, Studd JW (eds.). Current Management of the Menopause. CRC Press. pp. 95–98, 488. ISBN   978-0-203-48612-2.
  35. ↑ Laurtizen C (2001). "Hormone Substitution Before, During and After Menopause" (PDF). In Fisch FH (ed.). Menopause – Andropause: Hormone Replacement Therapy Through the Ages. Krause & Pachernegg: Gablitz. pp. 67–88. ISBN   978-3-901299-34-6.
  36. ↑ Midwinter A (1976). "Contraindications to estrogen therapy and management of the menopausal syndrome in these cases". In 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. ISBN   978-94-011-6167-1.
  37. ↑ 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 Pharmacologica Sinica. 22 (2): 148–154. PMID   11741520.
  38. 1 2 Greene RR, Dorr EM (1939). "Clinical use of a new estrogen". Endocrinology. 24 (4): 577–578. doi:10.1210/endo-24-4-577. ISSN   0013-7227.
  39. 1 2 Quirk Jr GJ, Wendell Jr GD (6 December 2012). "The Biological Effects of Natural and Synthetic Estrogens". In Buchsbaum HJ (ed.). The Menopause. Springer Science & Business Media. pp. 62–. ISBN   978-1-4612-5525-3.
  40. 1 2 3 4 5 Presl J, Hořejší J, Štroufová A, Herzmann J (1976). "Sexual maturation in girls and the development of estrogen induced gonadotropic hormone release". Annales de Biologie Animale, Biochimie, et Biophysique. 16 (3): 377–383. doi: 10.1051/rnd:19760314 . ISSN   0003-388X.
  41. 1 2 Schwartz MM, Soule SD (July 1955). "Estradiol 17-beta-cyclopentylpropionate, a longacting estrogen". American Journal of Obstetrics and Gynecology. 70 (1): 44–50. doi:10.1016/0002-9378(55)90286-6. PMID   14388061.
  42. ↑ "Estradiol Dipropionate | C24H32O4". ChemSpider.
  43. 1 2 Dorr EM, Greene RR (1939). "Treatment of the menopause with estradiol dipropionate". American Journal of Obstetrics and Gynecology. 38 (3): 458–464. doi:10.1016/S0002-9378(39)90763-5. ISSN   0002-9378.
  44. ↑ Reilly WA (November 1941). "Estrogens: Their Use in Pediatrics". California and Western Medicine. 55 (5): 237–239. PMC   1634235 . PMID   18746057.
  45. 1 2 Fluhmann CF (1944). "Clinical Use of Extracts from the Ovaries". Journal of the American Medical Association. 125 (1): 1. doi:10.1001/jama.1944.02850190003001. ISSN   0002-9955.
  46. ↑ Macpherson AI (June 1940). "The Use of Œstrogens in Obstetrics and Gynæcology". Edinburgh Medical Journal. 47 (6): 406–424. PMC   5306594 . PMID   29646930.
  47. ↑ Buschbeck 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. ISSN   0012-0472. S2CID   72668930.
  48. ↑ Greene RR (1941). "Endocrine Therapy for Gynecologic Disorders". Medical Clinics of North America. 25 (1): 155–168. doi:10.1016/S0025-7125(16)36624-X. ISSN   0025-7125.
  49. ↑ Oriowo MA, Landgren BM, Stenström B, Diczfalusy E (April 1980). "A comparison of the pharmacokinetic properties of three estradiol esters". Contraception. 21 (4): 415–424. doi:10.1016/S0010-7824(80)80018-7. PMID   7389356.
  50. ↑ Negwer M (1987). Organic-chemical Drugs and Their Synonyms: (an International Survey). VCH Publishers. p. 1272. ISBN   978-0-89573-552-2.
  51. ↑ International Agency for Research on Cancer (1979). Sex Hormones (II). International Agency for Research on Cancer. ISBN   978-92-832-1221-8.
  52. ↑ Lewis RJ (13 June 2008). Hazardous Chemicals Desk Reference. John Wiley & Sons. pp. 594–. ISBN   978-0-470-18024-2.
  53. ↑ Lissak K (6 December 2012). Hormones and Brain Function. Springer Science & Business Media. pp. 145–. ISBN   978-1-4684-2007-4.
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