Estradiol enantate

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Estradiol enantate
Estradiol enanthate.png
Estradiol enanthate molecule ball.png
Clinical data
Trade names Perlutal, Topasel, Unalmes, Yectames, others
Synonyms EE; E2E; E2-EN; EEn; Estradiol enanthate; Estradiol heptanoate; SQ-16150
Routes of
Intramuscular injection[1][2]
Drug class Estrogen; Estrogen ester
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability IM: High
Metabolism Cleavage via esterases in the liver, blood, and tissues[3][4]
Metabolites Estradiol, heptanoic acid, and metabolites of estradiol[3][4]
Elimination half-life IM: 5.6–7.5 days[5][1][6][7]
Excretion Urine[1]
CAS Number
PubChem CID
ECHA InfoCard 100.023.272 Edit this at Wikidata
Chemical and physical data
Formula C25H36O3
Molar mass 384.56 g/mol
3D model (JSmol)

Estradiol enantate, sold under the brand names Perlutal and Topasel among others, is an estrogen medication which is used in hormonal birth control.[1][2][8] It is formulated in combination with dihydroxyprogesterone acetophenide (DHPA; algestone acetophenide), a progestin, and is used as a combined injectable contraceptive.[1][2] Estradiol enantate is not available alone.[9][10][11][12] The medication is given by injection into muscle once a month.[1][2]

Side effects of estradiol enantate include breast tenderness, breast enlargement, nausea, headache, and fluid retention.[13] The drug is a synthetic estrogen and hence is an agonist of the estrogen receptor (ER), the biological target of estrogens like estradiol.[4][3] Estradiol enantate is an estrogen ester and a long-lasting prodrug of estradiol in the body.[3][4] Because of this, it is considered to be a natural and bioidentical form of estrogen.[3][14]

Estradiol enantate was first described by 1954,[15] and was first studied in combination with DHPA as a combined injectable contraceptive in 1964.[16][17] The combination was introduced for clinical use by the mid-1970s.[18][19][20] Estradiol enantate is not available as a standalone medication (i.e., by itself without DHPA).[12] The combination is available in Latin America and Hong Kong, and was also previously marketed in Spain and Portugal.[12][2][10]

Medical uses[edit]

Estradiol enantate is used in combination with the progestin DHPA as a once-monthly combined injectable contraceptive in Latin America and Hong Kong.[1][2][21][12] This combination has been said to also be used by "travestis" (a term for transgender women in some cultures, especially in South America) as a means of feminizing hormone therapy.[22]

Available forms[edit]

The following forms of estradiol enantate are or have been available for use:[8][23][24][20][2]

  • Estradiol enantate 10 mg and DHPA 150 mg (brand names Perlutal, Topasel, many others)
  • Estradiol enantate 5 mg and DHPA 75 mg (brand names Anafertin, Patector NF, Yectames)
  • Estradiol enantate 10 mg and DHPA 120 mg (brand names Unalmes, Yectuna)
  • Estradiol enantate 10 mg and DHPA 75 mg (brand name Ova Repos; discontinued)

A 6 mg estradiol enantate and 90 mg DHPA formulation was also studied, but was never marketed.[25][26][27] The combination of estradiol enantate and DHPA has also been studied at other doses ranging from 5 to 50 mg estradiol enantate and 75 to 200 mg DHPA.[28]

Side effects[edit]

The side effects of estradiol enantate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma.[13] The combination of estradiol enantate and DHPA has shown no adverse effects on liver function, lipid metabolism, or coagulation.[29][2]



Estradiol enantate is an estradiol ester, or a prodrug of estradiol.[3][4] As such, it is an estrogen, or an agonist of the estrogen receptors.[3][4] Estradiol enantate is of about 41% higher molecular weight than estradiol due to the presence of its C17β enantate ester.[30][12] Because estradiol enantate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.[3][14]

The combination of 10 mg estradiol enantate and 150 mg DHPA as a once-monthly combined injectable contraceptive (which achieves levels of estradiol of around 350 pg/mL)[31][32][33] has been found to have little to no effect on many markers of estrogen-modulated liver protein synthesis including circulating levels of HDL and LDL cholesterol, copper, ceruloplasmin, total and free cortisol, corticosteroid-binding globulin, and sex hormone-binding globulin.[34] However, it was found to significantly increase levels of triglycerides and to significantly decrease levels of total and free testosterone.[34] In contrast to the combined injectable contraceptive, an ethinylestradiol-containing birth control pill produced highly significant changes in all of the preceding parameters.[34]

The clinical estrogenic effects of estradiol enantate and ethinylestradiol have been compared in other studies as well.[35]


Idealized curves of estradiol levels over a period of 30 days after injection of different estradiol esters in women.[31] Four data points were used to generate the curves (day 0, peak day, a third day, and day 30).[31] The measurements from which the points were drawn were taken at 24-hour intervals.[31] The estradiol esters were given mostly as combined injectable contraceptives together with a progestin.[31]

When estradiol enantate is administered in an oil solution by intramuscular injection, a depot effect occurs, and this results in it having a long duration of action.[31][4][36] The duration of action of estradiol enantate is considerably longer than that of various other estradiol esters such as estradiol benzoate, estradiol valerate, and estradiol cypionate, whereas its duration is shorter than that of estradiol undecylate.[31][37][38] In general, the longer the fatty acid ester chain, the more lipophilic the estradiol ester, the more slowly it is released from the depot and absorbed into the circulation, and the longer its duration of action.[4][36]

The pharmacokinetics of estradiol enantate have been assessed in a number of studies.[31][39][32][5][33][40] It has usually been studied in combination with algestone acetophenide.[31][39][32][33] Following an intramuscular injection of estradiol enantate, levels of estradiol have been found to peak after 4 to 8 days.[31][33] Maximal levels of estradiol after a 5 mg injection of estradiol enantate have been found to be about 163 to 209 pg/mL and after a 10 mg injection about 283 to 445 pg/mL.[31][32][33] Estradiol levels have been found to return to baseline levels of about 50 pg/mL after around 30 days.[32][5][3][40] However, a metabolic study found that traces of radiolabeled estradiol enantate remained detectable in blood for at least 30 to 40 days and as long as 60 days.[39] Studies have reported that the elimination half-life of estradiol enantate after a single 10 mg intramuscular injection was 5.6 to 7.5 days.[5][1][6] The volume of distribution of estradiol enantate has been reported to be 5.087 L.[7] Estradiol enantate is excreted preferentially in urine.[19]

There have been concerns about possible accumulation of estradiol enantate and consequent estrogenic overexposure with once-monthly injection due to its long duration, and this may have limited its use.[6][31] However, in spite of this, clinical studies have found that there is very limited or no accumulation of estradiol enantate when used as a once-a-month injectable contraceptive in combination with DHPA.[6][29][2]


Estradiol enantate, also known as estradiol 17β-enantate or estra-1,3,5(10)-triene-3,17β-diol 17β-heptanoate, is a synthetic estrane steroid and the C17β enantate (heptanoate) fatty acid ester of estradiol.[30][12] Other common esters of estradiol used clinically include estradiol benzoate, estradiol cypionate, estradiol undecylate, and estradiol valerate.[12] Estradiol dienantate (component of Climacteron), or estradiol 3,17β-dienantate, has also been used.[30][41][42][43]


Estradiol enantate was first described in the literature by 1954.[15][44][45][38][46][47] The first clinical study of estradiol enantate and DHPA as a combined injectable contraceptive was conducted in 1964.[16][17] The combination was marketed by the mid-1970s.[18][19][20]

Society and culture[edit]

Generic names[edit]

Estradiol enantate is the English generic name of the drug and its INNM and BANM, while estradiol enanthate is its USAN.[30][12][9][48] Its generic names in other languages are as follows:[10][9]

Estradiol enantate is also known by its former developmental code name SQ-16150.[49] It has been referred to as estradiol heptanoate.[12][30][11][9][10]

Brand names[edit]

Estradiol enantate has been marketed under a wide variety of brand names.[10][9][50][51][8][52][24][53][20][2][31] It has been marketed in a few different preparations, with varying doses of estradiol enantate and DHPA.[24][8][52][23][20][2][31] These formulations all have different brand names, which include the following ( = discontinued):[10][9][50][51][23][24][8][52][2][54]

  • E2-EN 10 mg / DHPA 150 mg: Acefil, Agurin, Atrimon, Ciclomes, Ciclovar, Ciclovular, Cicnor, Clinomin, Cycloven, Daiva, Damix, Deprans, Deproxone, Exuna, Ginestest, Ginoplan, Gynomes, Horprotal, Listen, Luvonal, Neogestar, Neolutin, Nomagest, Nonestrol, Normagest, Normensil, Novular, Oterol, Ovoginal, Patector, Patectro, Perludil, Perlumes, Perlutal, Perlutale, Perlutan, Perlutin, Perlutin-Unifarma, Permisil, Preg-Less, Pregnolan, Progestrol, Protegin, Proter, Seguralmes, Synovular, Topasel, Unigalen, Uno-Ciclo, and Vagital.
  • E2-EN 10 mg / DHPA 120 mg: Anafertin, Patector NF, and Yectames.
  • E2-EN 5 mg / DHPA 75 mg: Unalmes and Yectuna.
  • E2-EN 10 mg / DHPA 75 mg: Ova Repos.
  • Unsorted: Evitas, Femineo, and Primyfar.

The combination of E2-EN 10 mg and DHPA 150 mg was developed under the developmental brand name Deladroxate, but this brand name was never used commercially.[20][2]


Known availability of estradiol enantate in countries throughout the world (as of September 2018).

Estradiol enantate (E2-EN) has been marketed in combination with DHPA as a combined injectable contraceptive in at least 19 countries, mostly in Latin America.[8][52][24][53][10][9][50][51] A few different preparations, with varying doses of E2-EN and DHPA and varying availability, have been introduced.[24][8][52][23][20][2][31] These formulations have the following approval and availability ( = discontinued in this country):[10][9][50][51][23][24][8][52][2]

E2-EN is also available in Canada in combination with estradiol benzoate and testosterone enantate for veterinary use as Uni-Bol.[55]


E2-EN/DHPA is the most widely used combined injectable contraceptive in Latin America.[56] It was estimated in 1995 that E2-EN/DHPA was used as a combined injectable contraceptive in Latin America by at least 1 million women.[24] However, combined injectable contraceptives like E2-EN/DHPA are unlikely to constitute a large proportion of contraceptive use in the countries in which they are available.[24]

See also[edit]


  1. ^ a b c d e f g h Jarquín González JD, Elda de Aguirre L, Rodríguez C, Abrego de Aguilar M, Carrillo F, León DA, Lima M, Trigueros S, Acosta R (September 1996). "Dihydroxyprogesterone acetophenide 150 mg + estradiol enantate 10 mg as monthly injectable contraceptives". Adv Contracept. 12 (3): 213–25. doi:10.1007/BF01849664. PMID 8910663.
  2. ^ a b c d e f g h i j k l m n o Newton JR, D'arcangues C, Hall PE (1994). "A review of "once-a-month" combined injectable contraceptives". J Obstet Gynaecol (Lahore). 4 Suppl 1: S1–34. doi:10.3109/01443619409027641. PMID 12290848.
  3. ^ a b c d e f g h i Michael Oettel; Ekkehard Schillinger (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. pp. 261, 271. 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. [...] Wiemeyer et al. (1986) measured elevated estradiol levels up to 31 days after an intramuscular dose of 10mg estradiol enanthate.
  4. ^ a b c d e f g h Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947.
  5. ^ a b c d Wiemeyer JC, Fernandez M, Moguilevsky JA, Sagasta CL (1986). "Pharmacokinetic studies of estradiol enantate in menopausic women". Arzneimittelforschung. 36 (11): 1674–7. PMID 3814225.
  6. ^ a b c d Sang GW (April 1994). "Pharmacodynamic effects of once-a-month combined injectable contraceptives". Contraception. 49 (4): 361–85. doi:10.1016/0010-7824(94)90033-7. PMID 8013220.
  7. ^ a b "Bula do Algestona Acetofenida + Enantato de Estradiol". Consulta Remédios. Archived from the original (HTML) on 2018-09-18. Retrieved 2018-09-18.
  8. ^ a b c d e f g h Bagade O, Pawar V, Patel R, Patel B, Awasarkar V, Diwate S (2014). "Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control" (PDF). World J Pharm Pharm Sci. 3 (10): 364–392. ISSN 2278-4357.
  9. ^ a b c d e f g h Sweetman, Sean C., ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2082. ISBN 978-0-85369-840-1.
  10. ^ a b c d e f g h
  11. ^ a b
  12. ^ a b c d e f g h i Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 405. ISBN 978-3-88763-075-1. Retrieved 20 May 2012.
  13. ^ a b Amit K. Ghosh (23 September 2010). Mayo Clinic Internal Medicine Board Review. OUP USA. pp. 222–. ISBN 978-0-19-975569-1.
  14. ^ a b Nagrath Arun; Malhotra Narendra; Seth Shikha (15 December 2012). Progress in Obstetrics and Gynecology--3. Jaypee Brothers Medical Publishers Pvt. Ltd. pp. 419–. ISBN 978-93-5090-575-3.
  15. ^ a b International Neurochemical Symposium (1954). Proceedings. Academic Press. p. 453.
  16. ^ a b Rutherford RN, Banks AL, Coburn WA (1964). "Deladroxate for the Prevention of Ovulation". Fertil. Steril. 15: 648–52. doi:10.1016/s0015-0282(16)35410-3. PMID 14236841.
  17. ^ a b Taymor ML, Planck S, Yahia C (1964). "Ovulation Inhibition with a Long-acting Parenteral Progestogen-Estrogen Combination". Fertil. Steril. 15: 653–60. doi:10.1016/s0015-0282(16)35411-5. PMID 14236842.
  18. ^ a b J. Bringer; B. Hedon (15 September 1995). Fertility and Sterility: A Current Overview. CRC Press. pp. 47–. ISBN 978-1-85070-694-6.
  19. ^ a b c Toppozada M (June 1977). "The clinical use of monthly injectable contraceptive preparations". Obstet Gynecol Surv. 32 (6): 335–47. doi:10.1097/00006254-197706000-00001. PMID 865726.
  20. ^ a b c d e f g Toppozada MK (April 1994). "Existing once-a-month combined injectable contraceptives". Contraception. 49 (4): 293–301. doi:10.1016/0010-7824(94)90029-9. PMID 8013216.
  21. ^ Zutshi (1 January 2005). Hormones in Obstetrics and Gynaecology. Jaypee Brothers Publishers. p. 138. ISBN 978-81-8061-427-9. Retrieved 20 May 2012.
  22. ^ Don Kulick (12 January 2009). Travesti: Sex, Gender, and Culture among Brazilian Transgendered Prostitutes. University of Chicago Press. pp. 64–66. ISBN 978-0-226-46101-4.
  23. ^ a b c d e IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; World Health Organization; International Agency for Research on Cancer (2007). Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy. World Health Organization. pp. 431–433, 467. ISBN 978-92-832-1291-1.
  24. ^ a b c d e f g h i IARC Working Group on the Evaluation of Carcinogenic Risks to Humans; International Agency for Research on Cancer (1 January 1999). Hormonal Contraception and Post-menopausal Hormonal Therapy (PDF). IARC. p. 65. ISBN 978-92-832-1272-0.
  25. ^ d’Arcangues, Catherine; Snow, Rachel C. (1999). "Injectable Contraceptives": 121–149. doi:10.1007/978-3-642-86696-8_6.
  26. ^ Coutinho EM, Spinola P, Barbosa I, Gatto M, Tomaz G, Morais K, Yazlle ME, de Souza RN, Pinho Neto JS, Leal Wde B, Leal C, Hippolito SB, Abranches AD (March 1997). "Multicenter, double-blind, comparative clinical study on the efficacy and acceptability of a monthly injectable contraceptive combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate compared to a monthly injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide and 6 mg estradiol enanthate". Contraception. 55 (3): 175–81. doi:10.1016/S0010-7824(97)00018-8. PMID 9115007.
  27. ^ Coutinho EM, Spinola P, Tomaz G, Morais K, Nassar de Souza R, Sabino Pinho Neto J, de Barros Leal W, Bomfim Hippolito S, D'Aurea Abranches A (April 2000). "Efficacy, acceptability, and clinical effects of a low-dose injectable contraceptive combination of dihydroxyprogesterone acetophenide and estradiol enanthate". Contraception. 61 (4): 277–80. doi:10.1016/S0010-7824(00)00099-8. PMID 10899484.
  28. ^ Koetsawang S (April 1994). "Once-a-month injectable contraceptives: efficacy and reasons for discontinuation". Contraception. 49 (4): 387–98. doi:10.1016/0010-7824(94)90034-5. PMID 8013221.
  29. ^ a b De Aguilar MA, Altamirano L, Leon DA, De Fung RC, Grillo AE, Gonzalez JD, Canales JR, Sanchez Jdel C, Pozuelos JL, Ramirez L, Rigionni R, Salgado JS, Torres L, Vallecillos G, Zambrano EJ, Zea C (December 1997). "Current status of injectable hormonal contraception, with special reference to the monthly method". Adv Contracept. 13 (4): 405–17. doi:10.1023/A:1006501526018. PMID 9404550.
  30. ^ a b c d e J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 898–. ISBN 978-1-4757-2085-3.
  31. ^ a b c d e f g h i j k l m n o Garza-Flores J (April 1994). "Pharmacokinetics of once-a-month injectable contraceptives". Contraception. 49 (4): 347–59. doi:10.1016/0010-7824(94)90032-9. PMID 8013219.
  32. ^ a b c d e Recio R, Garza-Flores J, Schiavon R, Reyes A, Diaz-Sanchez V, Valles V, Luz de la Cruz D, Oropeza G, Perez-Palacios G (June 1986). "Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive". Contraception. 33 (6): 579–89. doi:10.1016/0010-7824(86)90046-6. PMID 3769482.
  33. ^ a b c d e Schiavon R, Benavides S, Oropeza G, Garza-Flores J, Recio R, Díaz-Sanchez V, Pérez-Palacios G (June 1988). "Serum estrogens and ovulation return in chronic users of a once-a-month injectable contraceptive". Contraception. 37 (6): 591–8. doi:10.1016/0010-7824(88)90005-4. PMID 3396358.
  34. ^ a b c Wiemeyer JC, Sagasta CL, Roncales Mateo JM, Lavarello AC, Angel de Toro LA, Salas Diaz R (July 1990). "Multicentred clinical study of the metabolic effect of the monthly injectable contraceptive containing dihydroxyprogesterone acetophenide 150 mg + estradiol enanthate 10 mg". Contraception. 42 (1): 13–28. doi:10.1016/0010-7824(90)90088-D. PMID 2117515.
  35. ^ Moguilevsky JA, Wiemeyer JC, Sagasta CL, Leiderman S (November 1986). "Estrogenic activities of estradiol enantate and ethinylestradiol compared at a clinical level". Arzneimittelforschung. 36 (11): 1671–4. PMID 3101711.
  36. ^ a b Vermeulen A (1975). "Longacting steroid preparations". Acta Clin Belg. 30 (1): 48–55. doi:10.1080/17843286.1975.11716973. PMID 1231448.
  37. ^ Oriowo MA, Landgren BM, Stenström B, Diczfalusy E (1980). "A comparison of the pharmacokinetic properties of three estradiol esters". Contraception. 21 (4): 415–24. doi:10.1016/s0010-7824(80)80018-7. PMID 7389356.
  38. ^ a b Percy Roberts Wilde; Carey Franklin Coombs; Arthur J. Rendle Short (1959). The Medical Annual: A Year Book of Treatment and Practitioner's Index ... Publishing Science Group. As in the case of progestogens the esters of oestradiol vary in the duration of their effect. Oestradiol benzoate is short-acting (three days to a week). Oestradiol valerianate is somewhat longer-acting, and oestradiol enanthate and undecylate have considerably more prolonged duration of effectiveness. The undecylate may remain effective for some months, and should not be employed, [...]
  39. ^ a b c Gual, C.; Pérez-Palacios, G.; Pérez, A.E.; Ruiz, M.R.; Solis, J.; Cervantes, A.; Iramain, C.; Schreiber, E.C. (1973). "Metabolic fate of a long-acting injectable estrogen-progestogen contraceptive 1,2". Contraception. 7 (4): 271–287. doi:10.1016/0010-7824(73)90145-5. ISSN 0010-7824.
  40. ^ a b Garza-Flores J, Alba VM, Cravioto MC, Hernandez L, Perez-Palacios G, Alvarado G, Rivera R, Recio R, Bassol S (May 1989). "Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin". Contraception. 39 (5): 519–29. doi:10.1016/0010-7824(89)90107-8. PMID 2524362.
  41. ^ Ginsburg, Elizabeth S. (1999). "Androgen Replacement in Postmenopausal Women". In Seifer, David B.; Kennard, Elizabeth A. Menopause. 18. pp. 209–219. doi:10.1007/978-1-59259-246-3_13. ISBN 978-1-61737-129-5.
  42. ^ Robert B. Greenblatt; William E. Barfield; Edwin C. Jungck (January 1962). "The treatment of the menopause". Can Med Assoc J. 86 (3): 113–4. PMC 1848811. PMID 13901504.
  43. ^ David B. Seifer (27 July 1999). Menopause: Endocrinology and Management. Springer Science & Business Media. pp. 183–. doi:10.1007/978-1-59259-246-3. ISBN 978-1-59259-246-3.
  44. ^ Heinrich Waelsch (1955). Biochemistry of the Developing Nervous System: Proceedings. Academic Press. p. 453.
  45. ^ Acta Cytologica. International Academy of Cytology. 1958. p. 378.
  46. ^ Gauthier, B; Le Dreff, L; Aubry, R (1958). "Hormone derivatives of long-lasting action. I. Esters of estradiol". Annales Pharmaceutiques Francaises. 16: 757–66. ISSN 0003-4509. Treating 10 g. estradiol benzoate in 30 cc.dry C5H5N dropwise with 4.3 g. n-C6H13COCl (b20 71-2°), heating 1 hr. at 50-60°, pouring into 100 cc. 10% H2SO4, sepg. the oil after its solidification, washing with petr. ether, heating with 50 cc. MeOH, and cooling gave 10 g. 17-heptoyl-3β-benzoylestradiol, m. 95-8°. Dissolving 10 g. of this in 210 cc. 0.1N NaOH in MeOH and 40 cc. Me2CO with stirring, adding HCl to pH 7, filtering, evapg. in vacuo, and stirring the residue with petr. ether gave 7.9 g. 17-heptoyl-β-estradiol, m. 94-6° (iso-Pr2O). Adding to 5 g. estradiol stirred in 10 cc. anhyd. pyridine 8 g. n-C10H21COCl (b20 135-6°), keeping 1 hr. at 100°, cooling, adding 50 cc. 10% H2SO4, dissolving the sepd. ester in 50 cc. iso-Pr2O, washing with satd. NaHCO3 soln. and H2O, drying, and evapg. at room temp. gave 10.7 g. 3,17-diundecanoylestradiol, m. 48-9° (MeOH-Me2CO, then Me2O-Et2O), λmax. (0.005% in MeOH contg. 4% iso-Pr2O) 268 mμ, λmin. 282 and 250 mμ, inflexion 215 mμ. Stirring 8.8 g. estradiol divalerate in 90 cc. MeOH and 0.4 g. NaOH under N 210 min. to soln., adding 20% HCl to pH 7, evapg. in vacuo to 10 cc., keeping overnight at a low temp., and washing with H2O, MeOH, and petr. ether gave 4.4 g. 17-valeryl-β-estradiol, m. 145-6°, λmax. (0.005% in EtOH) 282 mμ, λmin. 248 mμ, inflexion 215 mμ. A single dose of 25 mg. of the diundecanate gave a therapeutic effect lasting 3 weeks.
  47. ^ 241206 ES 241206, "Esters of cortical hormones, androgens, or esterogens by transesterification and alcoholysis" 
  48. ^ I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 206–. ISBN 978-94-011-4439-1.
  49. ^ George W.A Milne (8 May 2018). Drugs: Synonyms and Properties: Synonyms and Properties. Taylor & Francis. pp. 1404–. ISBN 978-1-351-78989-9.
  50. ^ a b c d
  51. ^ a b c d
  52. ^ a b c d e f Pramilla Senanayake; Malcolm Potts (14 April 2008). Atlas of Contraception, Second Edition. CRC Press. pp. 50–. ISBN 978-0-203-34732-4.
  53. ^ a b Thomas Rabe; Benno Runnebaum (6 December 2012). Fertility Control — Update and Trends: Update and Trends. Springer Science & Business Media. pp. 183–. ISBN 978-3-642-86696-8. Two additional monthly, combined injectable methods warrant mention. Deladroxate (commercially labelled as Perlutan, Topasel, Agurin, Horprotal and Uno-Ciclo in various countries), is a combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate, and is available in many Latin American countries and Spain. The method is highly effective, without a single pregnancy reported in large clinical trials (Koetsawang 1994). Although available since the 1960s, the method has not been studied as extensively as Cyclofem or Mesigyna. The original manufacturer withdrew support due to toxicological concerns with dihydroxyprogesterone acetophenide, and clinical evaluations continue to be published. A recent dose-finding trial compared the standard available dose of 150/10 with a lower dose of 90/6, and concluded the lower dose was equally effective (Coutinho et al., 1997).
  54. ^ Gallo MF, Grimes DA, Lopez LM, Schulz KF, d'Arcangues C (2013). "Combination injectable contraceptives for contraception". Cochrane Database Syst Rev. 3: CD004568. doi:10.1002/14651858.CD004568.pub3. PMID 23641480.
  55. ^
  56. ^ Leon Speroff; Marc A. Fritz (2005). Clinical Gynecologic Endocrinology and Infertility. Lippincott Williams & Wilkins. pp. 969–. ISBN 978-0-7817-4795-0.