Estradiol undecylate explained

Iupac Name:[(8''R'',9''S'',13''S'',14''S'',17''S'')-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[''a'']phenanthren-17-yl] undecanoate
Width:250px
Width2:250px
Pronounce:
Tradename:Delestrec, Progynon Depot 100, others
Legal Status:Rx-only
Routes Of Administration:Intramuscular injection
Class:Estrogen
Estrogen ester
Bioavailability: injection: High
Protein Bound:Estradiol: ~98% (to albumin and)[1] [2]
Metabolism:Cleavage via esterases in the liver, blood, and tissues
Metabolites:Estradiol, undecanoic acid, estradiol metabolites
Elimination Half-Life:Unknown
Duration Of Action: injection:
• 10–12.5 mg: 1–2 months
• 25–50 mg: 2–4 months
Excretion:Urine
Cas Number:3571-53-7
Unii:H3N3A8MFJC
Atc Prefix:G03
Atc Suffix:CA03
Pubchem:19135
Chemspiderid:18055
Kegg:D04065
Chembl:1697794
Synonyms:EU; E2U; Estradiol undecanoate; Estradiol unducelate; RS-1047; SQ-9993
C:29
H:44
O:3
Smiles:CCCCCCCCCCC(=O)O[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=C3C=CC(=C4)O)C
Stdinchi:1S/C29H44O3/c1-3-4-5-6-7-8-9-10-11-28(31)32-27-17-16-26-25-14-12-21-20-22(30)13-15-23(21)24(25)18-19-29(26,27)2/h13,15,20,24-27,30H,3-12,14,16-19H2,1-2H3/t24-,25-,26+,27+,29+/m1/s1
Stdinchikey:TXHUMRBWIWWBGW-GVGNIZHQSA-N

Estradiol undecylate (EU, EUn, E2U), also known as estradiol undecanoate and formerly sold under the brand names Delestrec and Progynon Depot 100 among others, is an estrogen medication which has been used in the treatment of prostate cancer in men.[3] [4] [5] [6] [7] It has also been used as a part of hormone therapy for transgender women.[8] [9] [10] Although estradiol undecylate has been used in the past, it was discontinued.[11] The medication has been given by injection into muscle usually once a month.

Side effects of estradiol undecylate in men may include breast tenderness, breast development, feminization, sexual dysfunction, infertility, fluid retention, and cardiovascular issues. Estradiol undecylate is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol.[12] It is an estrogen ester and a very long-lasting prodrug of estradiol in the body.[13] Because of this, it is considered to be a natural and bioidentical form of estrogen.[14] An injection of estradiol undecylate has a duration of about 1 to 4 months.

Estradiol undecylate was first described in 1953 and was introduced for medical use by 1956. It remained in use as late as the 2000s before being discontinued. Estradiol undecylate was marketed in Europe, but does not seem to have ever been available in the United States. It was used for many years as a parenteral estrogen to treat prostate cancer in men, although it was not employed as often as polyestradiol phosphate.

Medical uses

Estradiol undecylate has been used as a form of high-dose estrogen therapy to treat prostate cancer, but has since largely been superseded for this indication by newer agents with fewer adverse effects (e.g., gynecomastia and cardiovascular complications) like analogues and nonsteroidal antiandrogens.[15] It has been assessed for this purpose in a number of clinical studies.[16] [17] [18] It has been used at a dosage of 100 mg every 3 to 4 weeks (or once a month) by intramuscular injection for this indication.[19]

Estradiol undecylate has been used to suppress sex drive in sex offenders.[20] It has been used for this indication at a dosage of 50 to 100 mg by intramuscular injection once every 3 to 4 weeks.

Estradiol undecylate has also been used to treat breast cancer in women.[21] It has been used in menopausal hormone therapy as well, for instance in the treatment of hot flashes and other menopausal symptoms. Along with estradiol valerate, estradiol cypionate, and estradiol benzoate, estradiol undecylate has been used as an intramuscular estrogen in feminizing hormone therapy for transgender women. It has been used at doses of 100 to as much as 800 mg per month by intramuscular injection for this purpose.

Available forms

Estradiol undecylate was available as an oil solution for intramuscular injection provided in ampoules at a concentration of 100 mg/mL.[22]

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.[23] [24] [25]

Side effects

Estradiol undecylate and its side effects have been evaluated for the treatment of advanced prostate cancer in a phase III international multicenter randomized controlled trial headed by Jacobi and colleagues of the Department of Urology, University of Mainz.[26] [27] [28] [29] [30] [31] [32] The study consisted of 191 patients from 12 treatment centers, who were treated for 6 months with intramuscular injections of either 100 mg/month estradiol undecylate (96 men) or 300 mg/week cyproterone acetate (95 men).[33] [34] Findings for a subgroup of 42 men at the University of Mainz center were initially reported in 1978 and 1980.[35] These men were age 51 to 84 years (mean 68 years), and men with pre-existing cardiovascular disease were excluded. A considerable incidence of cardiovascular complications was reported for the estradiol undecylate group (76%; 16/21 incidence total); there was a 67% (14/21) incidence of cardiovascular morbidity and a 9.5% (2/21) incidence of cardiovascular mortality.[36] The cardiovascular morbidity in this group included peripheral edema and superficial thrombophlebitis (38%; 8/21), coronary heart disease (24%; 5/21), and a deep vein thrombosis (4.8%; 1/21), while the cardiovascular mortality included a myocardial infarction (4.8%; 1/21) and a pulmonary embolism (4.8%; 1/21). Eight of the cases of cardiovascular complications in the estradiol undecylate group, including the two deaths, were regarded as "severe".[37] Conversely, no incidence of cardiovascular toxicity occurred in the cyproterone acetate comparison group (0%; 0/21). Other side effects of estradiol undecylate included gynecomastia (100%; 21/21) and erectile dysfunction (90%; 19/21). The cardiovascular complications with estradiol undecylate in this relatively small study are in contrast to large and high-quality clinical studies of high-dose polyestradiol phosphate and transdermal estradiol for prostate cancer, in which minimal to no cardiovascular toxicity has been observed.[38] [39] [40] [41] [42]

An expanded report of 191 patients, which included the 42 patients from the University of Mainz center plus an additional 149 patients from 11 other centers, was published in 1982. The antitumor effectiveness of estradiol undecylate and cyproterone acetate in this study was equivalent.[43] The rates of improvement, no response, and deterioration were 52%, 41%, and 7% in the estradiol undecylate group and 48%, 44%, and 8% in the cyproterone acetate group, respectively. However, the incidence of a selection of specific side effects, including gynecomastia, breast tenderness, and edema, was significantly lower in the cyproterone acetate group than in the estradiol undecylate group (37% vs. 94%, respectively).[44] Gynecomastia specifically occurred in 13% (12/96) of the patients in the cyproterone acetate group and 77% (73/95) of the patients in the estradiol undecylate group. Erectile dysfunction occurred in "essentially all" patients in both groups. Leg edema occurred in 18% (17/95) of the estradiol undecylate group and 4.2% (4/96) of the cyproterone acetate group, while the incidences of superficial thrombophlebitis and coronary heart disease both were not described. The incidence of thrombosis was 4.2% (4/95) in the estradiol undecylate group and 5.3% (5/96) in the cyproterone acetate group. There were five deaths in total, three in the estradiol undecylate group and two in the cyproterone acetate group. Two of the deaths in each of the treatment groups were due to cardiovascular events, while the remaining death in the estradiol undecylate group was due to unknown causes. The similar rate of cardiovascular complications besides edema between estradiol undecylate and cyproterone acetate that was observed is in contrast to the initial 42-patient report and to findings with other estrogens, such as diethylstilbestrol and estramustine phosphate, which have been shown to possess significantly higher cardiovascular toxicity than cyproterone acetate. On the basis of the expanded study, the researchers concluded that cyproterone acetate was an "acceptable alternative" to estrogen therapy with estradiol undecylate, but with a "considerably more favorable" side-effect profile.

After the completion of the initial expanded study, a 5-year extension trial primarily of the Ruhr University Bochum center subgroup, led by Tunn and colleagues, was conducted. In this study, the cyproterone acetate group was changed from intramuscular injections to 100 mg/day oral cyproterone acetate. Of the 39 patients in the study, the global 5-year survival rate was not significantly different between the estradiol undecylate and cyproterone acetate groups (24% and 26%, respectively). In patients without metastases, the 5-year survival rate was 51% in the cyproterone acetate group relative to 43% in the estradiol undecylate group, although the difference was not statistically significant. In terms of non-prostate cancer deaths, there were 5 in the CPA group and 6 in the EU group. The incidence of cardiovascular-related mortality was 3 deaths in the CPA group and 3 deaths in the EU group.

The side effects of estradiol undecylate have also been studied and reported beyond the preceding clinical trial programme and for other patient populations, for instance women. Side effects during therapy with massive doses of estradiol undecylate (200mg three times per week, or 600mg per week and around 2,400mg per month total) in postmenopausal women with advanced breast cancer have included appetite loss, nausea, vomiting, vaginal bleeding, vaginal discharge, nipple pigmentation, breast pain, rash, urinary incontinence, edema, drowsiness, hypercalcemia, and local injection-site reactions. Like with other estrogens, treatment with estradiol undecylate has been found to produce testicular abnormalities and disturbances of spermatogenesis in men.[45] In transgender women, estradiol undecylate by intramuscular injection at extremely high doses (200–800mg/month) was associated with greater incidence of hyperprolactinemia (high prolactin levels) than ethinylestradiol orally at a dose of 100μg/day (or about 3mg/month total) (rates of 40% and 16% for prolactin levels greater than 1,000mU/L, respectively). Switching from estradiol undecylate to ethinylestradiol resulted in a decrease in prolactin levels in many individuals. The preceding dosage of estradiol undecylate corresponds to much greater estrogenic exposure than the dosage of ethinylestradiol. Cyproterone acetate was also used in combination with estrogen in the study.

Overdose

Estradiol undecylate has been used clinically at massive doses of as much as 800 to 2,400 mg per month by intramuscular injection, given in divided doses of 100 to 200 mg per injection two to three times per week.[46] [47] [48] For purposes of comparison, a single 100 mg intramuscular injection of estradiol undecylate has been reported to produce estradiol levels of about 500 pg/mL. Symptoms of estrogen overdosage may include nausea, vomiting, bloating, increased weight, water retention, breast tenderness, vaginal discharge, heavy legs, and leg cramps.[49] These side effects can be diminished by reducing the estrogen dosage.

Interactions

Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels.[50]

Pharmacology

Pharmacodynamics

See also: Pharmacodynamics of estradiol.

Esters of estradiol like estradiol undecylate are readily hydrolyzed prodrugs of estradiol, but have an extended duration when administered in oil via intramuscular injection due to a depot effect afforded by their fatty acid ester moiety. As prodrugs of estradiol, estradiol undecylate and other estradiol esters are estrogens. Estradiol undecylate is of about 62% higher molecular weight than estradiol due to the presence of its C17β undecylate ester. Because estradiol undecylate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.

The effects of estradiol undecylate on cortisol, dehydroepiandrosterone sulfate, testosterone, prolactin, and sex hormone-binding globulin levels as well as on the hypothalamic–pituitary–adrenal axis have been studied in men with prostate cancer and compared with those of high-dose cyproterone acetate therapy.[51] [52] [53] [54] [55] [56] [57] [58] [59] The effects of estradiol undecylate on serum lipids and ceruloplasmin levels have been studied as well.[60] [61] [62] Additionally, the influence of estradiol undecylate on SHBG levels and free testosterone fraction in women has been described.

Antigonadotropic activity

A phase III clinical trial comparing high-dose intramuscular cyproterone acetate (300 mg/week) and high-dose intramuscular estradiol undecylate (100 mg/month) in the treatment of prostate cancer found that estradiol undecylate suppressed testosterone levels into the castrate range (< 50 ng/dL)[63] within at least 3 months whereas testosterone levels with cyproterone acetate were significantly higher and above the castrate range even after 6 months of treatment.[26] With estradiol undecylate, testosterone levels fell from 416 ng/dL to 38 ng/mL (–91%) after 3 months and to 29.6 ng/dL (–93%) after 6 months, whereas with cyproterone acetate, testosterone levels fell from 434 ng/dL to 107 ng/mL (–75%) at 3 months and to 102 ng/mL (–76%) at 6 months. In another study using the same dosages, estradiol undecylate suppressed testosterone levels by 97% while CPA suppressed them by 70%. In accordance, whereas estrogens are well-established as able to suppress testosterone levels into the castrate range at sufficiently high dosages,[64] progestogens like cyproterone acetate on their own are able to decrease testosterone levels only up to an apparent maximum of around 70 to 80%.[65] [66] Besides effects on testosterone levels, the long-term effects of estradiol undecylate on testicular morphology in transgender women have been studied.

Pharmacokinetics

See also: Pharmacokinetics of estradiol.

The pharmacokinetics of estradiol undecylate have been assessed limitedly in a few studies.[67] [68] [69] [70] [71] Following a single intramuscular injection of 100 mg estradiol undecylate in oil, mean levels of estradiol were about 500 pg/mL a day after injection and about 340 pg/mL 14 days after injection in 4people. Levels of estradiol with intramuscular estradiol undecylate were reported to be very irregular and to vary by as much as 10-fold between individuals. In another study, following a single intramuscular injection of 32.2 mg estradiol undecylate, levels of estradiol peaked at around 400 pg/mL after 3 days and decreased from this peak to around 200 pg/mL after 6 days in 3postmenopausal women. In a repeated administration study of 100 mg per month estradiol undecylate in 14men with prostate cancer, estradiol levels at trough were about 560 pg/mL at 3 months and about 540 pg/mL at 6 months following initiation of therapy. In a larger follow-up of the study with 21men, estradiol levels at trough were about 36pg/mL at baseline, 486pg/mL at 3months, and 598pg/mL at 6months of therapy. In one further study, levels of estradiol in an unspecified number of postmenopausal women following a single injection of 100mg estradiol undecylate were said to be between 300pg/mL and 600pg/mL six days post-injection.[72]

Due to its more protracted duration, doses of estradiol undecylate that are typical of other estradiol esters produce only "subthreshold" estradiol levels, and for this reason, higher single doses of estradiol undecylate are necessary for similar effects.[73] However, the relatively low levels of estradiol produced by lower doses of estradiol undecylate are favorable for menopausal replacement therapy.

The duration of estradiol undecylate is markedly prolonged relative to that of estradiol benzoate, estradiol valerate, and many other estradiol esters.[74] [75] [76] A single intramuscular injection of 10 to 12.5 mg estradiol undecylate has a duration of 40 to 60 days (~1–2 months) and of 25 to 50 mg estradiol undecylate has an estimated duration of effect of 2 to 4 months in postmenopausal women. A single intramuscular injection of 20 to 30 mg estradiol undecylate has been found to inhibit ovulation when used as an estrogen-only injectable contraceptive in premenopausal women for 1 to 3 months (mean 1.7 months) as well. When used at a higher dose of 100 mg per injection in men with prostate cancer, estradiol undecylate has been given usually once a month. After a single subcutaneous injection of estradiol undecylate in rats, its duration of effect was 80 days (about 2.5 months).[77] [78] [79] Due to its very prolonged duration, estradiol undecylate has been described in general as a favorable alternative to estradiol implants.

The excretion of estradiol undecylate has been studied as well.

Estradiol undecylate has not been used via oral administration. However, a closely related estradiol ester, estradiol decanoate (estradiol decylate), has been studied via the oral route, and has been found to possess significant oral bioavailability, to produce relatively high estradiol levels of about 100 pg/mL after a single 0.5 mg oral dose and about 100 to 150 pg/mL with continuous 0.25 mg/day oral therapy, and to have a much higher estradiol-to-estrone ratio than oral estradiol of about 2:1.[80] [81] [82] It is thought that this is due to absorption of estradiol decanoate by the lymphatic system and a consequent partial bypass of first-pass metabolism in the liver and intestines, which is similarly known to occur with oral testosterone undecanoate.[83] [84]

Chemistry

See also: Estrogen ester.

Estradiol undecylate is a synthetic estrane steroid and an estradiol ester. It is specifically the C17β undecylate (undecanoate) ester of estradiol. The compound is also known as estradiol 17β-undecylate or as estra-1,3,5(10)-triene-3,17β-diol 17β-undecanoate. The undecylic acid (undecanoic acid) ester of estradiol undecylate is a medium-chain fatty acid and is found naturally in many foods, some examples of which include coconut, fruits, fats, oils, and rice.[85]

Estradiol undecylate is a relatively long-chain ester of estradiol. Its undecylate ester contains 11 carbon atoms. For comparison, the ester chains of estradiol acetate, estradiol valerate, and estradiol enantate have 2, 5, and 7 carbon atoms, respectively. As a result of its longer ester chain, estradiol undecylate is the most lipophilic of these estradiol esters, and for this reason, has by far the longest duration when administered in oil solution by intramuscular injection.[86] [87] An example of an estradiol ester with a longer ester chain than estradiol undecylate is estradiol stearate (Depofollan), which has 18 carbon atoms and has been used in medicine as an estrogen as well.

A few estradiol esters related to estradiol undecylate include estradiol decanoate, estradiol diundecylate, and estradiol diundecylenate. Estradiol undecylate shares the same undecylate ester as testosterone undecanoate, an androgen/anabolic steroid and very long-lasting testosterone ester.

Estradiol undecylate is one of the longest-chain steroid esters that has been in common medical use.[88]

History

Estradiol undecylate was first described in the scientific literature, along with estradiol valerate and a variety of other estradiol esters, by Karl Junkmann of Schering AG in 1953.[89] [90] It was introduced for medical use via intramuscular injection by 1956.[91] [92] Syntex applied for a patent for estradiol undecylate in 1958, which was granted in 1961 and was given a priority date of 1957.[93] Estradiol undecylate was introduced for medical use and was employed for decades, but was eventually discontinued. It remained in use in some countries as late as the 2000s.

Harry Benjamin reported on the use of estradiol undecylate in transgender women in his book The Transsexual Phenomenon in 1966 and in a literature review in the Journal of Sex Research in 1967.[94]

Society and culture

Generic names

Estradiol undecylate is the generic name of the drug and its and . It is also spelled in some publications as estradiol unducelate and is also known as estradiol undecanoate. In German, it is known under a variety of spellings including as estradiolundecylat, östradiolundecylat, östradiolundezylat, oestradiolundecylat, oestradiolundezylat, and others.[95] Estradiol undecylate is known by its former developmental code names RS-1047 and SQ-9993 as well.

Brand names

The major brand name of estradiol undecylate is Progynon Depot 100. It has also been marketed under other brand names including Delestrec, Depogin, Estrolent, Oestradiol D, Oestradiol-Retard Theramex, and Primogyn Depot [0,1&nbsp;mg/ml], among others.[96]

Availability

Estradiol undecylate was available in the Europe (including in France, Germany, Great Britain, Monaco, the Netherlands, Switzerland), and Japan.[97] [98] [99] However, it has been discontinued and hence is no longer available.[100] [101]

Research

Estradiol undecylate was studied by Schering alone as an estrogen-only injectable contraceptive in premenopausal women at a dose of 20 to 30 mg once a month.[102] [103] [104] [105] It was effective, lacked breast and thromboembolic complications, lacked other side effects besides amenorrhea, and prevented ovulation for 1 to 3 months (mean 1.7 months) following a single dose. However, uterine growth of 1 to 2 cm was observed after one year, and endometrial hyperplasia was occasionally encountered.[103] The preparation was not further developed as a form of birth control due to the risks of endometrial hyperplasia and cancer associated with long-term unopposed estrogen therapy.

Estradiol undecylate, in combination with norethisterone enanthate (at doses of 5 to 10 mg and 50 to 70 mg, respectively), was studied by Schering as a combined injectable contraceptive in premenopausal women and was found to be effective and well-tolerated, but ultimately was not marketed for this use.[106] [107] [108] [109]

See also

Notes and References

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  9. Book: Benjamin H, Lal GB, Green R, Masters RE . The Transsexual Phenomenon. 1966. Ace Publishing Company. Another preparation of even higher potency is Squibb's Delestrec, which at this writing is not yet on the market in the United States, but is well known in Germany and other European countries under the name of Progynon Depot (Schering). It is chemically Estradiol Undecylate in oil, likewise slowly absorbing, and containing 100 mg. to 1 cc. Injections of 1 cc. once or twice a month can be sufficient. Occasionally, however, larger doses are required to influence the patient's emotional distress.. 107.
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  46. Asscheman H, Gooren LJ, Assies J, Smits JP, de Slegte R . Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexuals . Clinical Endocrinology . 28 . 6 . 583–588 . June 1988 . 2978262 . 10.1111/j.1365-2265.1988.tb03849.x . 29214187 .
  47. Asscheman H, Gooren LJ, Eklund PL . Mortality and morbidity in transsexual patients with cross-gender hormone treatment . Metabolism . 38 . 9 . 869–873 . September 1989 . 2528051 . 10.1016/0026-0495(89)90233-3 .
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  52. Book: Spona J, Lunglmayr G . Wiener Klinische Wochenschrift . Verhandlungsbericht der Deutschen Gesellschaft für Urologie . Prolaktin-Serumspiegel unter Behandlung des Prostatakarzinoms mit Östradiol-17 beta-undezylat und Cyproteronazetat . Serum Prolactin Levels During Therapy of Prostatic Cancer with Estradiol-17 beta-undecylate and Cyproterone Acetate . de . 92 . 14 . 494–7 . July 1980 . 6933738 . 10.1007/978-3-642-81706-9_120 . 978-3-540-11017-0 .
  53. Jacobi GH, Altwein JE . Bromocriptin als Palliativtherapie beim fortgeschrittenen Prostatakarzinom:Experimentelles und klinisches Profil eines Medikamentes . Urologia Internationalis . 34 . 4 . 266–290 . 1979 . 89747 . 10.1159/000280272 . Bromocriptine as Palliative Therapy in Advanced Prostate Cancer: Experimental and Clinical Profile of a Drug .
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  55. Book: Neumann F, El Etreby MF, Habenicht U, Radlmaier A, Bormacher K . Konservative Therapie des Prostatakarzinoms . Möglichkeiten des Androgenentzugs und der totalen Blockade . 1987 . 61–86. 10.1007/978-3-642-72613-2_6. 978-3-540-17724-1.
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  57. Book: Baba S, Janetschek G, Wenderoth U, Jacobi GH . Verhandlungsbericht der Deutschen Gesellschaft für Urologie. Beeinflussung des intraprostatischen Testosteron-Stoffwechsels durch Cyproteronazetat und Östradiolundecylat bei Patienten mit Prostatakarzinom: In vivo-Untersuchungen. Influence of intraprostatic testosterone metabolism by cyproterone acetate and estradiol undecylate in patients with prostate cancer: in vivo studies . 32. 1981. 464–466 . 10.1007/978-3-642-81706-9_138 . 978-3-540-11017-0.
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  68. Leyendecker G, Geppert G, Nocke W, Ufer J . [Estradiol-17beta, estrone, LH and FSH in serum after administration of estradiol-17beta, estradiolbenzoate, estradiol-valeriate and estradiol-undecylate in the female (author's transl)] ]. de . Geburtshilfe und Frauenheilkunde . 35 . 5 . 370–374 . May 1975 . 1150068 . Estradiol 17β, estrone, LH and FSH in serum after administration of estradiol 17β, estradiol benzoate, estradiol valeriate and estradiol undecylate in the female . Estradiol 17β, estradiol benzoate, estradiol valerianate, and estradiol undecylate were injected intravenously and intramuscularly to postmenopausal woman and to female castrates. Equal doses were used corresponding to 20 mg of free estradiol 17β. Estradiol 17β, estrone, FSH and LH were measured in serum by radioimmunoassay before and after application of the hormone and the estradiol esters. Thus the depot effect of the different esters could be compared. .
  69. Book: Geppert G . Untersuchungen zur Pharmakokinetik von Östradiol-17β, Östradiol-Benzoat, Östradiol-Valerianat und Östradiol-Undezylat bei der Frau: der Verlauf der Konzentrationen von Östradiol-17β, Östron, LH und FSH im Serum. Studies on the pharmacokinetics of estradiol-17β, estradiol benzoate, estradiol valerate, and estradiol undecylate in women: the progression of serum estradiol-17β, estrone, LH, and FSH concentrations. 1975. 632312599. 1–34.
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  73. Book: Jucker E . Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques. 8 March 2013. Birkhäuser. 978-3-0348-7044-3. 243–. Estradiol undecylenate has a more protracted effect but it releases only subthreshold doses of steroid (advantage may be taken of this for the treatment of menopause)..
  74. Book: Labhart A . Clinical Endocrinology: Theory and Practice. 6 December 2012. Springer Science & Business Media. 978-3-642-96158-8. 551–553.
  75. Book: Wilde PR, Coombs CF, Short AJ . The Medical Annual: A Year Book of Treatment and Practitioner's Index ... . 1959 . 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, [...].
  76. Book: International Society of Urology. Reports of the Congress. 1973. Livingstone. 252. Progynon-Depot ist eine Oestrogenpräparat mit einem Depoteffekt von 4-6 Wochen. 1 ml Progynon Depot 100 mg enthält 100 mg Oestra- diolundecylat in öliger Lösung. Oestradiolundecylat ist ein Ester des natürlichen Oestrogens Oestradiol..
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