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Estradiol undecylate

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Estradiol undecylate
Estradiol undecylate.svg
Estradiol undecylate molecule ball.png
Clinical data
Pronunciation/ˌɛstrəˈdɒl ənˈdɛsɪlt/
ES-trə-DY-ol un-DESS-il-ayt
Trade namesDelestrec, Progynon Depot 100, others
Other namesEU; E2U; Estradiol undecanoate; Estradiol unducelate; RS-1047; SQ-9993
Routes of
administration
Intramuscular injection[1]
Drug classEstrogen; Estrogen ester
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityIM injection: High
Protein bindingEstradiol: ~98% (to albumin and SHBG)[2][3]
MetabolismCleavage via esterases in the liver, blood, and tissues[4][5]
MetabolitesEstradiol, undecanoic acid, estradiol metabolites[4][5]
Elimination half-lifeUnknown
Duration of actionIM injection:
• 10–12.5 mg: 1–2 months[6][7]
• 25–50 mg: 2–4 months[8]
ExcretionUrine
Identifiers
  • [(8R,9S,13S,14S,17S)-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] undecanoate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.020.616 Edit this at Wikidata
Chemical and physical data
FormulaC29H44O3
Molar mass440.668 g·mol−1
3D model (JSmol)
  • InChI=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
  • Key:TXHUMRBWIWWBGW-GVGNIZHQSA-N

Estradiol undecylate (EU or 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.[9][10][11][12][1] It has also been used as a part of hormone therapy for transgender women.[13][14][15] Although estradiol undecylate has been used in the past, it was discontinued and hence is no longer available.[11][16] The medication has been given by injection into muscle usually once a month.[1][17][12]

Side effects of estradiol undecylate in men may include breast tenderness, breast development, feminization, sexual dysfunction, infertility, fluid retention, and cardiovascular issues.[17] Estradiol undecylate 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 very long-lasting prodrug of estradiol in the body.[4][5] Because of this, it is considered to be a natural and bioidentical form of estrogen.[4][18][19] An injection of estradiol undecylate has a duration of about 1 to 4 months.[7][8][6][20]

Estradiol undecylate was first described in 1953 and was introduced for medical use by 1956.[7][21][8][22] It remained in use as late as the 2000s before being discontinued.[23][11][24] Estradiol undecylate was marketed in Europe, but does not seem to have ever been available in the United States.[14][25][11] 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.[12]

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Estrogen (medication)

Estrogen (medication)

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

Gynecomastia

Gynecomastia

Gynecomastia is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Gynecomastia can cause significant psychological distress or unease.

Feminization (biology)

Feminization (biology)

In biology and medicine, feminization is the development in an organism of physical characteristics that are usually unique to the female of the species. This may represent a normal developmental process, contributing to sexual differentiation. Feminization can also be induced by environmental factors, and this phenomenon has been observed in several animal species. In the case of transgender hormone therapy, it is intentionally induced artificially.

Agonist

Agonist

An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist.

Estrogen receptor

Estrogen receptor

Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors, which are members of the nuclear receptor family of intracellular receptors, and membrane estrogen receptors (mERs), which are mostly G protein-coupled receptors. This article refers to the former (ER).

Biological target

Biological target

A biological target is anything within a living organism to which some other entity is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets are proteins and nucleic acids. The definition is context-dependent, and can refer to the biological target of a pharmacologically active drug compound, the receptor target of a hormone, or some other target of an external stimulus. Biological targets are most commonly proteins such as enzymes, ion channels, and receptors.

Estrogen

Estrogen

Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy.

Estradiol

Estradiol

Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips and a female-associated pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus and vagina during puberty, adulthood and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain.

Estrogen ester

Estrogen ester

An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens such as estrone, estriol, and even nonsteroidal estrogens like diethylstilbestrol. Esterification renders estradiol into a prodrug of estradiol with increased resistance to first-pass metabolism, slightly improving its oral bioavailability. In addition, estrogen esters have increased lipophilicity, which results in a longer duration when given by intramuscular or subcutaneous injection due to the formation of a long-lasting local depot in muscle and fat. Conversely, this is not the case with intravenous injection or oral administration. Estrogen esters are rapidly hydrolyzed into their parent estrogen by esterases once they have been released from the depot. Because estradiol esters are prodrugs of estradiol, they are considered to be natural and bioidentical forms of estrogen.

Estradiol (medication)

Estradiol (medication)

Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.

Bioidentical hormone replacement therapy

Bioidentical hormone replacement therapy

Bioidentical hormone replacement therapy (BHRT), also known as bioidentical hormone therapy (BHT) or natural hormone therapy, is the use of hormones that are identical on a molecular level with endogenous hormones in hormone replacement therapy. It may also be combined with blood and saliva testing of hormone levels, and the use of pharmacy compounding to obtain hormones in an effort to reach a targeted level of hormones in the body. A number of claims by some proponents of BHT have not been confirmed through scientific testing. Specific hormones used in BHT include estrone, estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA), and estriol.

Europe

Europe

Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. Comprising the westernmost peninsulas of Eurasia, it shares the continental landmass of Afro-Eurasia with both Africa and Asia. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south and Asia to the east. Europe is commonly considered to be separated from Asia by the watershed of the Ural Mountains, the Ural River, the Caspian Sea, the Greater Caucasus, the Black Sea and the waterways of the Turkish Straits.

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 GnRH analogues and nonsteroidal antiandrogens.[1][26] It has been assessed for this purpose in a number of clinical studies.[27][28][29][30][31] 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.[17][32]

Estradiol undecylate has been used to suppress sex drive in sex offenders.[33] It has been used for this indication at a dosage of 50 to 100 mg by intramuscular injection once every 3 to 4 weeks.[33]

Estradiol undecylate has also been used to treat breast cancer in women.[34] It has been used in menopausal hormone therapy as well, for instance in the treatment of hot flashes and other menopausal symptoms.[8] 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.[13][14][15] It has been used at doses of 100 to as much as 800 mg per month by intramuscular injection for this purpose.[14][15][13][35][36][37]

Estrogen dosages for prostate cancer
Route/form Estrogen Dosage
Oral Estradiol 1–2 mg 3x/day
Conjugated estrogens 1.25–2.5 mg 3x/day
Ethinylestradiol 0.15–3 mg/day
Ethinylestradiol sulfonate 1–2 mg 1x/week
Diethylstilbestrol 1–3 mg/day
Dienestrol 5 mg/day
Hexestrol 5 mg/day
Fosfestrol 100–480 mg 1–3x/day
Chlorotrianisene 12–48 mg/day
Quadrosilan 900 mg/day
Estramustine phosphate 140–1400 mg/day
Transdermal patch Estradiol 2–6x 100 μg/day
Scrotal: 1x 100 μg/day
IM or SC injection Estradiol benzoate 1.66 mg 3x/week
Estradiol dipropionate 5 mg 1x/week
Estradiol valerate 10–40 mg 1x/1–2 weeks
Estradiol undecylate 100 mg 1x/4 weeks
Polyestradiol phosphate Alone: 160–320 mg 1x/4 weeks
With oral EE: 40–80 mg 1x/4 weeks
Estrone 2–4 mg 2–3x/week
IV injection Fosfestrol 300–1200 mg 1–7x/week
Estramustine phosphate 240–450 mg/day
Note: Dosages are not necessarily equivalent. Sources: See template.

Available forms

Estradiol undecylate was available as an oil solution for intramuscular injection provided in ampoules at a concentration of 100 mg/mL.[23][38]

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High-dose estrogen

High-dose estrogen

High-dose estrogen (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of a progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and progestogen levels achieved are in the range of the very high levels of these hormones that occur during pregnancy. HDE and pseudopregnancy have been used in medicine for a number of hormone-dependent indications, such as breast cancer, prostate cancer, and endometriosis, among others. Both natural or bioidentical estrogens and synthetic estrogens have been used and both oral and parenteral routes may be used.

Prostate cancer

Prostate cancer

Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that surrounds the urethra just below the bladder. It is located in the hypogastric region of the abdomen. To give an idea of where it is located, the bladder is superior to the prostate gland as shown in the image The rectum is posterior in perspective to the prostate gland and the ischial tuberosity of the pelvic bone is inferior. Only those who have male reproductive organs are able to get prostate cancer. Most prostate cancers are slow growing. Cancerous cells may spread to other areas of the body, particularly the bones and lymph nodes. It may initially cause no symptoms. In later stages, symptoms include pain or difficulty urinating, blood in the urine, or pain in the pelvis or back. Benign prostatic hyperplasia may produce similar symptoms. Other late symptoms include fatigue, due to low levels of red blood cells.

Adverse effect

Adverse effect

An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not a complication. Adverse effects are sometimes referred to as "iatrogenic" because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment. Adverse effects can also be caused by placebo treatments . Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may cause complications of a disease or procedure and negatively affect its prognosis. They may also lead to non-compliance with a treatment regimen. Adverse effects of medical treatment resulted in 142,000 deaths in 2013 up from 94,000 deaths in 1990 globally.

Gynecomastia

Gynecomastia

Gynecomastia is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Gynecomastia can cause significant psychological distress or unease.

Nonsteroidal antiandrogen

Nonsteroidal antiandrogen

A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens like testosterone and dihydrotestosterone (DHT). NSAAs are used in the treatment of androgen-dependent conditions in men and women. They are the converse of steroidal antiandrogens (SAAs), which are antiandrogens that are steroids and are structurally related to testosterone.

Intramuscular injection

Intramuscular injection

Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have larger and more numerous blood vessels than subcutaneous tissue, leading to faster absorption than subcutaneous or intradermal injections. Medication administered via intramuscular injection is not subject to the first-pass metabolism effect which affects oral medications.

Breast cancer

Breast cancer

Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.

Hot flash

Hot flash

Hot flashes are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and may typically last from two to 30 minutes for each occurrence.

Estradiol valerate

Estradiol valerate

Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy for menopausal symptoms and low estrogen levels, hormone therapy for transgender people, and in hormonal birth control. It is also used in the treatment of prostate cancer. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.

Estradiol cypionate

Estradiol cypionate

Estradiol cypionate (EC), sold under the brand name Depo-Estradiol among others, is an estrogen medication which is used in hormone therapy for menopausal symptoms and low estrogen levels in cis women, in hormone therapy for trans women, and in hormonal birth control for cis women. It is given by injection into muscle once every 1 to 4 weeks.

Estradiol benzoate

Estradiol benzoate

Estradiol benzoate (EB), sold under the brand name Progynon-B among others, is an estrogen medication which is used in hormone therapy for menopausal symptoms and low estrogen levels in women, in hormone therapy for transgender women, and in the treatment of gynecological disorders. It is also used in the treatment of prostate cancer in men. Estradiol benzoate is used in veterinary medicine as well. When used clinically, the medication is given by injection into muscle usually two to three times per week.

Feminizing hormone therapy

Feminizing hormone therapy

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

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.[39][40][41][42]

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Contraindication

Contraindication

In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain treatment.

Coagulation

Coagulation

Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.

Cardiovascular disease

Cardiovascular disease

Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction. Other CVDs include stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis.

Liver disease

Liver disease

Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.

Hormone-sensitive cancer

Hormone-sensitive cancer

A hormone-sensitive cancer, or hormone-dependent cancer, is a type of cancer that is dependent on a hormone for growth and/or survival. Examples include breast cancer, which is dependent on estrogens like estradiol, and prostate cancer, which is dependent on androgens like testosterone.

Breast cancer

Breast cancer

Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.

Endometrial cancer

Endometrial cancer

Endometrial cancer is a cancer that arises from the endometrium. It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.

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.[17][43][44][45][46][28][47] 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).[43][45][46][28][47][48][49] Findings for a subgroup of 42 men at the University of Mainz center were initially reported in 1978 and 1980.[50][17][28][47] These men were age 51 to 84 years (mean 68 years), and men with pre-existing cardiovascular disease were excluded.[12][17][51] 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.[12][17][51] 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).[17][51] Eight of the cases of cardiovascular complications in the estradiol undecylate group, including the two deaths, were regarded as "severe".[51][52] Conversely, no incidence of cardiovascular toxicity occurred in the cyproterone acetate comparison group (0%; 0/21).[12][17][51] Other side effects of estradiol undecylate included gynecomastia (100%; 21/21) and erectile dysfunction (90%; 19/21).[17] 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.[53][54][55][56][57]

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.[43][49] The antitumor effectiveness of estradiol undecylate and cyproterone acetate in this study was equivalent.[43][45][58][46][28][47] 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.[43][46] 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).[43][45][46][59] 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.[43][45] Erectile dysfunction occurred in "essentially all" patients in both groups.[49] 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.[43] The incidence of thrombosis was 4.2% (4/95) in the estradiol undecylate group and 5.3% (5/96) in the cyproterone acetate group.[43][48][49] There were five deaths in total, three in the estradiol undecylate group and two in the cyproterone acetate group.[43] 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.[43][46][49] 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.[45] 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.[46]

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.[29][44][45][28][48][47] In this study, the cyproterone acetate group was changed from intramuscular injections to 100 mg/day oral cyproterone acetate.[29][45] 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).[29][45][28][48][47] 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.[29][45] In terms of non-prostate cancer deaths, there were 5 in the CPA group and 6 in the EU group.[29] The incidence of cardiovascular-related mortality was 3 deaths in the CPA group and 3 deaths in the EU group.[29]

Side effects of estradiol undecylate versus cyproterone acetate in men
Side effect Estradiol undecylate
100 mg/month i.m. (n = 96)
Cyproterone acetate
100 mg/day oral (n = 95)
n % n %
Gynecomastia* 74 77.1% 12 12.6%
Breast tenderness* 84 87.5% 6 6.3%
Sexual impotence
"Occurred in essentially all patients of both groups"
Leg edema* 17 17.7% 4 4.2%
Thrombosis 4 4.2% 5 5.3%
Cardiovascular mortality 2 2.1% 2 2.1%
Other mortality 1a 1.0% 0 0%
Notes: For 6 months in 191 men age 51 to 88 years with prostate cancer. Footnotes: * = Differences in incidences between groups were statistically significant. a = Due to unknown causes. Sources: See template.

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 (200 mg three times per week, or 600 mg per week and around 2,400 mg 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.[34] Like with other estrogens, treatment with estradiol undecylate has been found to produce testicular abnormalities and disturbances of spermatogenesis in men.[60] In transgender women, estradiol undecylate by intramuscular injection at extremely high doses (200–800 mg/month) was associated with greater incidence of hyperprolactinemia (high prolactin levels) than ethinylestradiol orally at a dose of 100 μg/day (or about 3 mg/month total) (rates of 40% and 16% for prolactin levels greater than 1,000 mU/L, respectively).[35] Switching from estradiol undecylate to ethinylestradiol resulted in a decrease in prolactin levels in many individuals.[35] The preceding dosage of estradiol undecylate corresponds to much greater estrogenic exposure than the dosage of ethinylestradiol.[35] Cyproterone acetate was also used in combination with estrogen in the study.[35]

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Multicenter trial

Multicenter trial

A multicenter research trial is a clinical trial conducted at more than one medical center or clinic. Most large clinical trials, particularly Phase III trials, are conducted at several clinical research centers.

Randomized controlled trial

Randomized controlled trial

A randomized controlled trial is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical techniques, medical devices, diagnostic procedures or other medical treatments.

Intramuscular injection

Intramuscular injection

Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have larger and more numerous blood vessels than subcutaneous tissue, leading to faster absorption than subcutaneous or intradermal injections. Medication administered via intramuscular injection is not subject to the first-pass metabolism effect which affects oral medications.

Cyproterone acetate

Cyproterone acetate

Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender women, and in birth control pills. It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

Mortality rate

Mortality rate

Mortality rate, or death rate, is a measure of the number of deaths in a particular population, scaled to the size of that population, per unit of time. Mortality rate is typically expressed in units of deaths per 1,000 individuals per year; thus, a mortality rate of 9.5 in a population of 1,000 would mean 9.5 deaths per year in that entire population, or 0.95% out of the total. It is distinct from "morbidity", which is either the prevalence or incidence of a disease, and also from the incidence rate.

Peripheral edema

Peripheral edema

Peripheral edema is edema in tissues perfused by the peripheral vascular system, usually in the lower limbs. In the most dependent parts of the body, it may be called dependent edema.

Deep vein thrombosis

Deep vein thrombosis

Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enlarged veins in the affected area, but some DVTs have no symptoms. The most common life-threatening concern with DVT is the potential for a clot to embolize, travel as an embolus through the right side of the heart, and become lodged in a pulmonary artery that supplies blood to the lungs. This is called a pulmonary embolism (PE). DVT and PE comprise the cardiovascular disease of venous thromboembolism (VTE). About two-thirds of VTE manifests as DVT only, with one-third manifesting as PE with or without DVT. The most frequent long-term DVT complication is post-thrombotic syndrome, which can cause pain, swelling, a sensation of heaviness, itching, and in severe cases, ulcers. Recurrent VTE occurs in about 30% of those in the ten years following an initial VTE.

Myocardial infarction

Myocardial infarction

A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck or jaw. Often it occurs in the center or left side of the chest and lasts for more than a few minutes. The discomfort may occasionally feel like heartburn. Other symptoms may include shortness of breath, nausea, feeling faint, a cold sweat or feeling tired. About 30% of people have atypical symptoms. Women more often present without chest pain and instead have neck pain, arm pain or feel tired. Among those over 75 years old, about 5% have had an MI with little or no history of symptoms. An MI may cause heart failure, an irregular heartbeat, cardiogenic shock or cardiac arrest.

Pulmonary embolism

Pulmonary embolism

Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathing in, and coughing up blood. Symptoms of a blood clot in the leg may also be present, such as a red, warm, swollen, and painful leg. Signs of a PE include low blood oxygen levels, rapid breathing, rapid heart rate, and sometimes a mild fever. Severe cases can lead to passing out, abnormally low blood pressure, obstructive shock, and sudden death.

Gynecomastia

Gynecomastia

Gynecomastia is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Gynecomastia can cause significant psychological distress or unease.

Erectile dysfunction

Erectile dysfunction

Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men. Through its connection to self-image and to problems in sexual relationships, erectile dysfunction can cause psychological harm.

Polyestradiol phosphate

Polyestradiol phosphate

Polyestradiol phosphate (PEP), sold under the brand name Estradurin, is an estrogen medication which is used primarily in the treatment of prostate cancer in men. It is also used in women to treat breast cancer, as a component of hormone therapy to treat low estrogen levels and menopausal symptoms, and as a component of feminizing hormone therapy for transgender women. It is given by injection into muscle once every four weeks.

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.[34][15][35][36][37] For purposes of comparison, a single 100 mg intramuscular injection of estradiol undecylate has been found to produce maximal estradiol levels of about 500 pg/mL.[61] Symptoms of estrogen overdosage may include nausea, vomiting, bloating, increased weight, water retention, breast tenderness, vaginal discharge, heavy legs, and leg cramps.[39] These side effects can be diminished by reducing the estrogen dosage.[39]

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Nausea

Nausea

Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.

Vomiting

Vomiting

Vomiting is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.

Bloating

Bloating

Abdominal bloating is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, pressure or fullness in the stomach; it may or may not be accompanied by a visibly distended abdomen. Bloating can affect anyone of any age range and is usually self-diagnosed, in most cases does not require serious medical attention or treatment. Although this term is usually used interchangeably with abdominal distension, these symptoms probably have different pathophysiological processes, which are not fully understood.

Weight gain

Weight gain

Weight gain is an increase in body weight. This can involve an increase in muscle mass, fat deposits, excess fluids such as water or other factors. Weight gain can be a symptom of a serious medical condition.

Vaginal discharge

Vaginal discharge

Vaginal discharge is a mixture of liquid, cells, and bacteria that lubricate and protect the vagina. This mixture is constantly produced by the cells of the vagina and cervix, and it exits the body through the vaginal opening. The composition, amount, and quality of discharge varies between individuals and can vary throughout the menstrual cycle and throughout the stages of sexual and reproductive development. Normal vaginal discharge may have a thin, watery consistency or a thick, sticky consistency, and it may be clear or white in color. Normal vaginal discharge may be large in volume but typically does not have a strong odor, nor is it typically associated with itching or pain. While most discharge is considered physiologic or represents normal functioning of the body, some changes in discharge can reflect infection or other pathological processes. Infections that may cause changes in vaginal discharge include vaginal yeast infections, bacterial vaginosis, and sexually transmitted infections. The characteristics of abnormal vaginal discharge vary depending on the cause, but common features include a change in color, a foul odor, and associated symptoms such as itching, burning, pelvic pain, or pain during sexual intercourse.

Heavy legs

Heavy legs

Heavy legs is a condition described as an unpleasant sensation of pain and heaviness in the lower limbs. Symptoms include legs feeling weighted, stiff, and tired.

Interactions

Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels.[62]

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Enzyme inhibitor

Enzyme inhibitor

An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction.

Enzyme inducer

Enzyme inducer

An enzyme inducer is a type of drug that increases the metabolic activity of an enzyme either by binding to the enzyme and activating it, or by increasing the expression of the gene coding for the enzyme. It is the opposite of an enzyme repressor.

Cytochrome P450

Cytochrome P450

Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones.

Metabolism

Metabolism

Metabolism is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary metabolism.

Pharmacology

Estradiol, the active form of estradiol undecylate.
Estradiol, the active form of estradiol undecylate.

Pharmacodynamics

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.[5] As prodrugs of estradiol, estradiol undecylate and other estradiol esters are estrogens.[4][5] Estradiol undecylate is of about 62% higher molecular weight than estradiol due to the presence of its C17β undecylate ester.[9][11] Because estradiol undecylate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.[4][18][19]

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.[63][64][65][66][67][68][17][69][70][66][71] The effects of estradiol undecylate on serum lipids and ceruloplasmin levels have been studied as well.[72][73][74] Additionally, the influence of estradiol undecylate on SHBG levels and free testosterone fraction in women has been described.[75]

Potencies and durations of natural estrogens by intramuscular injection
Estrogen Form Dose (mg) Duration by dose (mg)
EPD CICD
Estradiol Aq. soln. ?
Oil soln. 40–60 1–2 ≈ 1–2 d
Aq. susp. ? 3.5 0.5–2 ≈ 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 dipropionate Oil soln. 25–30 5 ≈ 5–8 d
Estradiol valerate Oil soln. 20–30 5 5 ≈ 7–8 d; 10 ≈ 10–14 d;
40 ≈ 14–21 d; 100 ≈ 21–28 d
Estradiol benz. butyrate Oil soln. ? 10 10 ≈ 21 d
Estradiol cypionate Oil soln. 20–30 5 ≈ 11–14 d
Aq. susp. ? 5 5 ≈ 14–24 d
Estradiol enanthate Oil soln. ? 5–10 10 ≈ 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.

Antigonadotropic activity

Testosterone levels with 300 mg/week cyproterone acetate or 100 mg/month estradiol undecylate both by intramuscular injection.[17] The solid lines are the average levels and the dashed lines are the highest and lowest observed levels.
Testosterone levels with 300 mg/week cyproterone acetate or 100 mg/month estradiol undecylate both by intramuscular injection.[17] The solid lines are the average levels and the dashed lines are the highest and lowest observed levels.
Estradiol, testosterone, and prolactin levels with 100 mg/month estradiol undecylate by intramuscular injection in men with prostate cancer.[65]
Estradiol, testosterone, and prolactin levels with 100 mg/month estradiol undecylate by intramuscular injection in men with prostate cancer.[65]

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 ([76] 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.[17] 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.[17] In another study using the same dosages, estradiol undecylate suppressed testosterone levels by 97% while CPA suppressed them by 70%.[68] In accordance, whereas estrogens are well-established as able to suppress testosterone levels into the castrate range at sufficiently high dosages,[77] progestogens like cyproterone acetate on their own are able to decrease testosterone levels only up to an apparent maximum of around 70 to 80%.[78][79] Besides effects on testosterone levels, the long-term effects of estradiol undecylate on testicular morphology in transgender women have been studied.[60]

Pharmacokinetics

The pharmacokinetics of estradiol undecylate have been assessed limitedly in a few studies.[80][81][82][83][65][84][7][8] 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 4 people.[80] Levels of estradiol with intramuscular estradiol undecylate were reported to be very irregular and to vary by as much as 10-fold between individuals.[80] 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 3 postmenopausal women.[81][85] In a repeated administration study of 100 mg per month estradiol undecylate in 14 men 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.[65] In a larger follow-up of the study with 21 men, estradiol levels at trough were about 36 pg/mL at baseline, 486 pg/mL at 3 months, and 598 pg/mL at 6 months of therapy.[66] In one further study, levels of estradiol in an unspecified number of postmenopausal women following a single injection of 100 mg estradiol undecylate were said to be between 300 pg/mL and 600 pg/mL six days post-injection.[75]

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.[86][80][81] However, the relatively low levels of estradiol produced by lower doses of estradiol undecylate are favorable for menopausal replacement therapy.[86]

The duration of estradiol undecylate is markedly prolonged relative to that of estradiol benzoate, estradiol valerate, and many other estradiol esters.[61][6][20][18] 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.[7][8][6][20] 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.[87] 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.[17][32] After a single subcutaneous injection of estradiol undecylate in rats, its duration of effect was 80 days (about 2.5 months).[88][89][90] Due to its very prolonged duration, estradiol undecylate has been described in general as a favorable alternative to estradiol implants.[8]

The excretion of estradiol undecylate has been studied as well.[83]

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.[91][92][93] 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,[91][92][93] which is similarly known to occur with oral testosterone undecanoate.[94][95]

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Estradiol (medication)

Estradiol (medication)

Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.

Active metabolite

Active metabolite

An active metabolite is an active form of a drug after it has been processed by the body.

Hydrolysis

Hydrolysis

Hydrolysis is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.

Intramuscular injection

Intramuscular injection

Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have larger and more numerous blood vessels than subcutaneous tissue, leading to faster absorption than subcutaneous or intradermal injections. Medication administered via intramuscular injection is not subject to the first-pass metabolism effect which affects oral medications.

Depot injection

Depot injection

A depot injection is a term for an injection formulation of a medication which releases slowly over time to permit less frequent administration of a medication. They are designed to increase medication adherence and consistency, especially in patients who commonly forget to take their medicine. Depot injections can be created by modifying the drug molecule itself, as in the case of prodrugs, or by modifying the way it is administered, as in the case of oil/lipid suspensions. Depot injections can have a duration of action of one month or greater and are available for many types of drugs, including antipsychotics and hormones.

Fatty acid

Fatty acid

In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters: triglycerides, phospholipids, and cholesteryl esters. In any of these forms, fatty acids are both important dietary sources of fuel for animals and important structural components for cells.

Moiety (chemistry)

Moiety (chemistry)

In organic chemistry, a moiety is a part of a molecule that is given a name because it is identified as a part of other molecules as well.

Natural product

Natural product

A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients.

Bioidentical hormone replacement therapy

Bioidentical hormone replacement therapy

Bioidentical hormone replacement therapy (BHRT), also known as bioidentical hormone therapy (BHT) or natural hormone therapy, is the use of hormones that are identical on a molecular level with endogenous hormones in hormone replacement therapy. It may also be combined with blood and saliva testing of hormone levels, and the use of pharmacy compounding to obtain hormones in an effort to reach a targeted level of hormones in the body. A number of claims by some proponents of BHT have not been confirmed through scientific testing. Specific hormones used in BHT include estrone, estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA), and estriol.

Cortisol

Cortisol

Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.

Dehydroepiandrosterone sulfate

Dehydroepiandrosterone sulfate

Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepiandrosterone (DHEA) and circulates in far greater relative concentrations than DHEA. The steroid is hormonally inert and is instead an important neurosteroid and neurotrophin.

Hypothalamic–pituitary–adrenal axis

Hypothalamic–pituitary–adrenal axis

The hypothalamic–pituitary–adrenal axis is a complex set of direct influences and feedback interactions among three components: the hypothalamus, the pituitary gland, and the adrenal glands. These organs and their interactions constitute the HPA axis.

Chemistry

Estradiol undecylate is a synthetic estrane steroid and an estradiol ester.[9][10] It is specifically the C17β undecylate (undecanoate) ester of estradiol.[9][10][11] The compound is also known as estradiol 17β-undecylate or as estra-1,3,5(10)-triene-3,17β-diol 17β-undecanoate.[10][11] 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.[97]

Estradiol undecylate is a relatively long-chain ester of estradiol.[10][11] Its undecylate ester contains 11 carbon atoms.[10][11] For comparison, the ester chains of estradiol acetate, estradiol valerate, and estradiol enantate have 2, 5, and 7 carbon atoms, respectively.[10][11] 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.[61][98][99] An example of an estradiol ester with a longer ester chain that 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.[9][10] Estradiol undecylate shares the same undecylate ester as testosterone undecanoate, an androgen/anabolic steroid and very long-lasting testosterone ester.[9][10]

Estradiol undecylate is one of the longest-chain steroid esters that has been in common medical use.[100]

Structural properties of selected estradiol esters
Estrogen Structure Ester(s) Relative
mol. weight
Relative
E2 contentb
log Pc
Position(s) Moiet(ies) Type Lengtha
Estradiol
Estradiol.svg
1.00 1.00 4.0
Estradiol acetate
Estradiol 3-acetate.svg
C3 Ethanoic acid Straight-chain fatty acid 2 1.15 0.87 4.2
Estradiol benzoate
Estradiol benzoate.svg
C3 Benzenecarboxylic acid Aromatic fatty acid – (~4–5) 1.38 0.72 4.7
Estradiol dipropionate
Estradiol dipropionate.svg
C3, C17β Propanoic acid (×2) Straight-chain fatty acid 3 (×2) 1.41 0.71 4.9
Estradiol valerate
Estradiol valerate.svg
C17β Pentanoic acid Straight-chain fatty acid 5 1.31 0.76 5.6–6.3
Estradiol benzoate butyrate
Estradiol butyrate benzoate.svg
C3, C17β Benzoic acid, butyric acid Mixed fatty acid – (~6, 2) 1.64 0.61 6.3
Estradiol cypionate
Estradiol 17 beta-cypionate.svg
C17β Cyclopentylpropanoic acid Aromatic fatty acid – (~6) 1.46 0.69 6.9
Estradiol enanthate
Estradiol enanthate.png
C17β Heptanoic acid Straight-chain fatty acid 7 1.41 0.71 6.7–7.3
Estradiol dienanthate
Estradiol dienanthate.svg
C3, C17β Heptanoic acid (×2) Straight-chain fatty acid 7 (×2) 1.82 0.55 8.1–10.4
Estradiol undecylate
Estradiol undecylate.svg
C17β Undecanoic acid Straight-chain fatty acid 11 1.62 0.62 9.2–9.8
Estradiol stearate
Estradiol stearate structure.svg
C17β Octadecanoic acid Straight-chain fatty acid 18 1.98 0.51 12.2–12.4
Estradiol distearate
Estradiol distearate.svg
C3, C17β Octadecanoic acid (×2) Straight-chain fatty acid 18 (×2) 2.96 0.34 20.2
Estradiol sulfate
Estradiol sulfate.svg
C3 Sulfuric acid Water-soluble conjugate 1.29 0.77 0.3–3.8
Estradiol glucuronide
Estradiol sulfate.svg
C17β Glucuronic acid Water-soluble conjugate 1.65 0.61 2.1–2.7
Estramustine phosphated
Estramustine phosphate.svg
C3, C17β Normustine, phosphoric acid Water-soluble conjugate 1.91 0.52 2.9–5.0
Polyestradiol phosphatee
Polyestradiol phosphate.svg
C3–C17β Phosphoric acid Water-soluble conjugate 1.23f 0.81f 2.9g
Footnotes: a = Length of ester in carbon atoms for straight-chain fatty acids or approximate length of ester in carbon atoms for aromatic 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.

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Estrogen ester

Estrogen ester

An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens such as estrone, estriol, and even nonsteroidal estrogens like diethylstilbestrol. Esterification renders estradiol into a prodrug of estradiol with increased resistance to first-pass metabolism, slightly improving its oral bioavailability. In addition, estrogen esters have increased lipophilicity, which results in a longer duration when given by intramuscular or subcutaneous injection due to the formation of a long-lasting local depot in muscle and fat. Conversely, this is not the case with intravenous injection or oral administration. Estrogen esters are rapidly hydrolyzed into their parent estrogen by esterases once they have been released from the depot. Because estradiol esters are prodrugs of estradiol, they are considered to be natural and bioidentical forms of estrogen.

Estrane

Estrane

Estrane is a C18 steroid derivative, with a gonane core.

Ester

Ester

In chemistry, an ester is a compound derived from an oxoacid in which at least one hydroxyl group is replaced by an alkoxy group, as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are fatty acid esters of glycerol; they are important in biology, being one of the main classes of lipids and comprising the bulk of animal fats and vegetable oils.

Estradiol (medication)

Estradiol (medication)

Estradiol (E2) is a medication and naturally occurring steroid hormone. It is an estrogen and is used mainly in menopausal hormone therapy and to treat low sex hormone levels in women. It is also used in hormonal birth control for women, in hormone therapy for transgender women, and in the treatment of hormone-sensitive cancers like prostate cancer in men and breast cancer in women, among other uses. Estradiol can be taken by mouth, held and dissolved under the tongue, as a gel or patch that is applied to the skin, in through the vagina, by injection into muscle or fat, or through the use of an implant that is placed into fat, among other routes.

Natural product

Natural product

A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients.

Coconut

Coconut

The coconut tree is a member of the palm tree family (Arecaceae) and the only living species of the genus Cocos. The term "coconut" can refer to the whole coconut palm, the seed, or the fruit, which botanically is a drupe, not a nut. The name comes from the old Portuguese word coco, meaning "head" or "skull", after the three indentations on the coconut shell that resemble facial features. They are ubiquitous in coastal tropical regions and are a cultural icon of the tropics.

Fruit

Fruit

In botany, a fruit is the seed-bearing structure in flowering plants that is formed from the ovary after flowering.

Fat

Fat

In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.

Carbon

Carbon

Carbon is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon makes up only about 0.025 percent of Earth's crust. Three isotopes occur naturally, 12C and 13C being stable, while 14C is a radionuclide, decaying with a half-life of about 5,730 years. Carbon is one of the few elements known since antiquity.

Atom

Atom

Every atom is composed of a nucleus and one or more electrons bound to the nucleus. The nucleus is made of one or more protons and a number of neutrons. Only the most common variety of hydrogen has no neutrons.

Estradiol acetate

Estradiol acetate

Estradiol acetate (EA), sold under the brand names Femtrace, Femring, and Menoring, is an estrogen medication which is used in hormone therapy for the treatment of menopausal symptoms in women. It is taken by mouth once daily or given as a vaginal ring once every three months.

Estradiol valerate

Estradiol valerate

Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy for menopausal symptoms and low estrogen levels, hormone therapy for transgender people, and in hormonal birth control. It is also used in the treatment of prostate cancer. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.

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.[101][7] It was introduced for medical use via intramuscular injection by 1956.[21][8][22] Syntex applied for a patent for estradiol undecylate in 1958, which was granted in 1961 and was given a priority date of 1957.[23][102] Estradiol undecylate was introduced for medical use and was employed for decades, but was eventually discontinued.[11][25][38] It remained in use in some countries as late as the 2000s.[23][11][24]

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.[14][103]

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Scientific literature

Scientific literature

Scientific literature comprises scholarly publications that report original empirical and theoretical work in the natural and social sciences. Within an academic field, scientific literature is often referred to as the literature. Academic publishing is the process of contributing the results of one's research into the literature, which often requires a peer-review process.

Estradiol valerate

Estradiol valerate

Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy for menopausal symptoms and low estrogen levels, hormone therapy for transgender people, and in hormonal birth control. It is also used in the treatment of prostate cancer. The medication is taken by mouth or by injection into muscle or fat once every 1 to 4 weeks.

Schering AG

Schering AG

Schering AG was a research-centered German multinational pharmaceutical company headquartered in Wedding, Berlin, which operated as an independent company from 1851 to 2006. In 2006, it was bought by Bayer AG and merged to form the Bayer subsidiary Bayer Schering Pharma AG, which was renamed Bayer HealthCare Pharmaceuticals in 2011. Schering was listed on the Frankfurt Stock Exchange and had 26,000 employees as of 2004.

Intramuscular injection

Intramuscular injection

Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have larger and more numerous blood vessels than subcutaneous tissue, leading to faster absorption than subcutaneous or intradermal injections. Medication administered via intramuscular injection is not subject to the first-pass metabolism effect which affects oral medications.

Syntex

Syntex

Laboratorios Syntex SA was a pharmaceutical company formed in Mexico City in January 1944 by Russell Marker, Emeric Somlo, and Federico Lehmann to manufacture therapeutic steroids from the Mexican yams called cabeza de negro and Barbasco. The demand for barbasco by Syntex initiated the Mexican barbasco trade.

Patent

Patent

A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention. In most countries, patent rights fall under private law and the patent holder must sue someone infringing the patent in order to enforce their rights. In some industries patents are an essential form of competitive advantage; in others they are irrelevant.

Harry Benjamin

Harry Benjamin

Harry Benjamin was a German-American endocrinologist and sexologist, widely known for his clinical work with transgender people.

Journal of Sex Research

Journal of Sex Research

The Journal of Sex Research is a peer-reviewed academic journal covering the study of human sexuality and the field of sexology in general. It is published by Routledge on behalf of the Society for the Scientific Study of Sexuality. In 1963, the society had published a one-issue journal entitled Advances in Sex Research. The Journal of Sex Research was then first published in 1965. The current editor-in-chief is Cynthia A. Graham.

Society and culture

Generic names

Estradiol undecylate is the generic name of the drug and its INN and USAN.[9][10][11][16] It is also spelled in some publications as estradiol unducelate and is also known as estradiol undecanoate.[61][9][10][11][16] In German, it is known under a variety of spellings including as estradiolundecylat, östradiolundecylat, östradiolundezylat, oestradiolundecylat, oestradiolundezylat, and others.[104] Estradiol undecylate is known by its former developmental code names RS-1047 and SQ-9993 as well.[9][10][11][16]

Brand names

The major brand name of estradiol undecylate is Progynon Depot 100.[9][10][11] It has also been marketed under other brand names including Delestrec, Depogin, Estrolent, Oestradiol D, Oestradiol-Retard Theramex, and Primogyn Depot [0,1 mg/ml], among others.[9][10][11][23][24]

Availability

Estradiol undecylate was available in the Europe (including in France, Germany, Great Britain, Monaco, the Netherlands, Switzerland), and Japan.[11][23][105][22][106] However, it has been discontinued and hence is no longer available.[25][38]

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United States Adopted Name

United States Adopted Name

A United States Adopted Name (USAN) is a unique nonproprietary name assigned to a medication marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association (AMA), the United States Pharmacopeial Convention (USP), and the American Pharmacists Association (APhA).

German language

German language

German is a West Germanic language of the Indo-European language family, mainly spoken in Central Europe. It is the most widely spoken and official or co-official language in Germany, Austria, Switzerland, Liechtenstein, and the Italian province of South Tyrol. It is also a co-official language of Luxembourg and Belgium, as well as a national language in Namibia. Outside Germany, it is also spoken by German communities in France (Bas-Rhin), Czech Republic, Poland, Slovakia, and Hungary (Sopron).

Europe

Europe

Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a subcontinent of Eurasia and it is located entirely in the Northern Hemisphere and mostly in the Eastern Hemisphere. Comprising the westernmost peninsulas of Eurasia, it shares the continental landmass of Afro-Eurasia with both Africa and Asia. It is bordered by the Arctic Ocean to the north, the Atlantic Ocean to the west, the Mediterranean Sea to the south and Asia to the east. Europe is commonly considered to be separated from Asia by the watershed of the Ural Mountains, the Ural River, the Caspian Sea, the Greater Caucasus, the Black Sea and the waterways of the Turkish Straits.

France

France

France, officially the French Republic, is a transcontinental country predominantly located in Western Europe and spanning overseas regions and territories in the Americas and the Atlantic, Pacific and Indian Oceans. Its metropolitan area extends from the Rhine to the Atlantic Ocean and from the Mediterranean Sea to the English Channel and the North Sea; overseas territories include French Guiana in South America, Saint Pierre and Miquelon in the North Atlantic, the French West Indies, and many islands in Oceania and the Indian Ocean. Due to its several coastal territories, France has the largest exclusive economic zone in the world. France borders Belgium, Luxembourg, Germany, Switzerland, Monaco, Italy, Andorra, and Spain in continental Europe, as well as the Netherlands, Suriname, and Brazil in the Americas via its overseas territories in French Guiana and Saint Martin. Its eighteen integral regions span a combined area of 643,801 km2 (248,573 sq mi) and contain close to 68 million people. France is a unitary semi-presidential republic with its capital in Paris, the country's largest city and main cultural and commercial centre; other major urban areas include Marseille, Lyon, Toulouse, Lille, Bordeaux, and Nice.

Germany

Germany

Germany, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated between the Baltic and North seas to the north, and the Alps to the south; it covers an area of 357,022 square kilometres (137,847 sq mi), with a population of almost 84 million within its 16 constituent states. Germany borders Denmark to the north, Poland and the Czech Republic to the east, Austria and Switzerland to the south, and France, Luxembourg, Belgium, and the Netherlands to the west. The nation's capital and most populous city is Berlin and its financial centre is Frankfurt; the largest urban area is the Ruhr.

Great Britain

Great Britain

Great Britain is an island in the North Atlantic Ocean off the northwest coast of continental Europe. With an area of 209,331 km2 (80,823 sq mi), it is the largest of the British Isles, the largest European island and the ninth-largest island in the world. It is dominated by a maritime climate with narrow temperature differences between seasons. The 60% smaller island of Ireland is to the west—together with these islands, along with over 1,000 smaller surrounding islands and named substantial rocks, form the British Isles archipelago.

Monaco

Monaco

Monaco, officially the Principality of Monaco, is a sovereign city-state and microstate on the French Riviera a few kilometres west of the Italian region of Liguria, in Western Europe, on the Mediterranean Sea. It is bordered by France to the north, east and west. The principality is home to 38,682 residents, of whom 9,486 are Monégasque nationals; it is widely recognised as one of the most expensive and wealthiest places in the world. The official language of the principality is French. In addition, Monégasque, Italian and English are spoken and understood by many residents.

Netherlands

Netherlands

The Netherlands, informally Holland, is a country located in Northwestern Europe with overseas territories in the Caribbean. It is the largest of four constituent countries of the Kingdom of the Netherlands. The Netherlands consists of twelve provinces; it borders Germany to the east, Belgium to the south, with a North Sea coastline to the north and west. It shares maritime borders with the United Kingdom, Germany and Belgium in the North Sea. The country's official language is Dutch, with West Frisian as a secondary official language in the province of Friesland. Dutch Low Saxon and Limburgish are recognised regional languages, while Dutch Sign Language, Sinte Romani and Yiddish are recognised non-territorial languages. Dutch, English and Papiamento are official in the Caribbean territories.

Switzerland

Switzerland

Switzerland, officially the Swiss Confederation;, is a landlocked country located at the confluence of Western, Central and Southern Europe. It is a federal republic composed of 26 cantons, with federal authorities based in Bern.

Japan

Japan

Japan is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north toward the East China Sea, Philippine Sea, and Taiwan in the south. Japan is a part of the Ring of Fire, and spans an archipelago of 6852 islands covering 377,975 square kilometers (145,937 sq mi); the five main islands are Hokkaido, Honshu, Shikoku, Kyushu, and Okinawa. Tokyo is the nation's capital and largest city, followed by Yokohama, Osaka, Nagoya, Sapporo, Fukuoka, Kobe, and Kyoto.

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.[85][87][107][108] 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.[87] However, uterine growth of 1 to 2 cm was observed after one year, and endometrial hyperplasia was occasionally encountered.[85][87][107] 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.[87]

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.[109][108][87][110][111][112]

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Schering AG

Schering AG

Schering AG was a research-centered German multinational pharmaceutical company headquartered in Wedding, Berlin, which operated as an independent company from 1851 to 2006. In 2006, it was bought by Bayer AG and merged to form the Bayer subsidiary Bayer Schering Pharma AG, which was renamed Bayer HealthCare Pharmaceuticals in 2011. Schering was listed on the Frankfurt Stock Exchange and had 26,000 employees as of 2004.

Breast

Breast

The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues.

Side effect

Side effect

In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug. Developing drugs is a complicated process, because no two people are exactly the same, so even drugs that have virtually no side effects, might be difficult for some people. Also, it is difficult to make a drug that targets one part of the body but that does not affect other parts, the fact that increases the risk of side effects in the untargeted parts.

Amenorrhea

Amenorrhea

Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses during childhood and after menopause.

Ovulation

Ovulation

Ovulation is the release of eggs from the ovaries. In women, this event occurs when the ovarian follicles rupture and release the secondary oocyte ovarian cells. After ovulation, during the luteal phase, the egg will be available to be fertilized by sperm. In addition, the uterine lining (endometrium) is thickened to be able to receive a fertilized egg. If no conception occurs, the uterine lining as well as the egg will be shed during menstruation.

Endometrial hyperplasia

Endometrial hyperplasia

Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.

Endometrial cancer

Endometrial cancer

Endometrial cancer is a cancer that arises from the endometrium. It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most often vaginal bleeding not associated with a menstrual period. Other symptoms include pain with urination, pain during sexual intercourse, or pelvic pain. Endometrial cancer occurs most commonly after menopause.

Norethisterone enanthate

Norethisterone enanthate

Norethisterone enanthate (NETE), also known as norethindrone enanthate, is a form of hormonal birth control which is used to prevent pregnancy in women. It is used both as a form of progestogen-only injectable birth control and in combined injectable birth control formulations. It may be used following childbirth, miscarriage, or abortion. The failure rate per year in preventing pregnancy for the progestogen-only formulation is 2 per 100 women. Each dose of this form lasts two months with only up to two doses typically recommended.

Tolerability

Tolerability

Tolerability refers to the degree to which overt adverse effects of a drug can be tolerated by a patient. Tolerability of a particular drug can be discussed in a general sense, or it can be a quantifiable measurement as part of a clinical study. Usually, it is measured by the rate of "dropouts", or patients that forfeit participation in a study due to extreme adverse effects. Tolerability, however, is often relative to the severity of the medical condition a drug is designed to treat. For instance, cancer patients may tolerate significant pain or discomfort during a chemotherapeutic study with the hope of prolonging survival or finding a cure, whereas patients experiencing a benign condition, such as a headache, are less likely to.

Source: "Estradiol undecylate", Wikipedia, Wikimedia Foundation, (2022, November 27th), https://en.wikipedia.org/wiki/Estradiol_undecylate.

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References
  1. ^ a b c d Zink C (1 January 1988). Dictionary of Obstetrics and Gynecology. Walter de Gruyter. p. 85. ISBN 978-3-11-085727-6.
  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. ^ Falcone T, Hurd WW (2007). Clinical Reproductive Medicine and Surgery. Elsevier Health Sciences. pp. 22, 362, 388. ISBN 978-0-323-03309-1.
  4. ^ a b c d e f g Oettel M, Schillinger E (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. p. 261,544. 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. ^ a b c d e f 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. ^ a b c d Labhart A (6 December 2012). Clinical Endocrinology: Theory and Practice. Springer Science & Business Media. pp. 551–553. ISBN 978-3-642-96158-8.
  7. ^ a b c d e f Wied GL (January 1954). "[Estradiol valerate and estradiol undecylate, two new estrogens with prolonged action; comparison with estradiol benzoate]" [Estradiol valerate and estradiol undecylate, two new estrogens with prolonged action; comparison with estradiol benzoate]. Geburtshilfe und Frauenheilkunde (in German). 14 (1): 45–52. PMID 13142295.
  8. ^ a b c d e f g h Gouygou C, Gueritee N, Pye A (1956). "[A fat-soluble, delayed estrogen : the estradiol undecylate]" [A fat-soluble, delayed estrogen: the estradiol undecylate]. Therapie (in French). 11 (5): 909–917. PMID 13391788.
  9. ^ a b c d e f g h i j k 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.
  10. ^ a b c d e f g h i j k l m n Roberts AD (1991). Dictionary of Steroids: Chemical Data, Structures, and Bibliographies. CRC Press. p. 415. ISBN 978-0-412-27060-4. Retrieved 20 May 2012.
  11. ^ a b c d e f g h i j k l m n o p q r Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. p. 405. ISBN 978-3-88763-075-1. Retrieved 20 May 2012.
  12. ^ a b c d e f Norman G, Dean ME, Langley RE, Hodges ZC, Ritchie G, Parmar MK, et al. (February 2008). "Parenteral oestrogen in the treatment of prostate cancer: a systematic review". British Journal of Cancer. 98 (4): 697–707. doi:10.1038/sj.bjc.6604230. PMC 2259178. PMID 18268497.
  13. ^ a b c Schlatterer K, von Werder K, Stalla GK (1996). "Multistep treatment concept of transsexual patients". Experimental and Clinical Endocrinology & Diabetes. 104 (6): 413–419. doi:10.1055/s-0029-1211479. PMID 9021341.
  14. ^ a b c d e Benjamin H, Lal GB, Green R, Masters RE (1966). The Transsexual Phenomenon. Ace Publishing Company. p. 107. 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.
  15. ^ a b c d Israel GE (March 2001). Transgender Care: Recommended Guidelines, Practical Information, and Personal Accounts. Temple University Press. pp. 64–. ISBN 978-1-56639-852-7.
  16. ^ a b c d "Estradiol".
  17. ^ a b c d e f g h i j k l m n o Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R (June 1980). "Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial". British Journal of Urology. 52 (3): 208–215. doi:10.1111/j.1464-410x.1980.tb02961.x. PMID 7000222.
  18. ^ a b c International Society of Urology (1973). Reports of the Congress. Livingstone. p. 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.
  19. ^ a b Lembeck F, Sewing KF (7 March 2013). Pharmakologie-Fibel: Tafeln zur Pharmakologie-Vorlesung. Springer-Verlag. pp. 113–. ISBN 978-3-642-65621-7.
  20. ^ a b c Wilde PR, Coombs CF, Short AJ (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, [...]
  21. ^ a b Halkerston ID, Hillman J, Palmer D, Rundle A (July 1956). "Changes in the excretion pattern of neutral 17-ketosteroids during oestrogen administration to male subjects". The Journal of Endocrinology. 13 (4): 433–438. doi:10.1677/joe.0.0130433. PMID 13345960.
  22. ^ a b c Bishop PM (1958). "Endocrine Treatment of Gynaecological Disorders". In Gardiner-Hill H (ed.). Modern Trends in Endocrinology. Modern Trends. Vol. 1. London: Butterworth & Co. pp. 231–244.
  23. ^ a b c d e f Kleemann A, Engel J, Kutscher B, Reichert D (2009). Pharmaceutical Substances: Syntheses, Patents and Applications of the most relevant APIs (5th ed.). Thieme. pp. 1167–1174. ISBN 978-3-13-179525-0.
  24. ^ a b c Index Nominum: International Drug Directory. CRC Press. 2004. pp. 469–. ISBN 978-3-88763-101-7.
  25. ^ a b c "Micromedex".
  26. ^ Mutschler E, Derendorf H (1995). Drug Actions: Basic Principles and Therapeutic Aspects. CRC Press. p. 609. ISBN 978-0-8493-7774-7. Retrieved 30 January 2013.
  27. ^ Enfedjieff M (March 1974). "[Experiences with hormonal treatment of prostatic carcinoma]" [Experiences with hormonal treatment of prostatic carcinoma]. Zeitschrift Fur Urologie und Nephrologie (in German). 67 (3): 171–173. PMID 4848715. Archived from the original on 2018-11-23. Treatment of prostatic carcinoma in 256 patients using parenteral injections of Progynon Depot (a depto estradiol preparation) is reproted. 58% of patients survived 3 or more years from beginning of treatment, and in 70% therapeutic results were considered good with regression of tumor mass, reduction or disappearance of pain, normalization of miction, and improved general status. Results of estrogen treatment are evident within 3 months in most cases. Side effects include gynecomastia in 95% of cases, impotence in almost all patients, and atrophic changes in the testicles, which may actually be desirable. Prostatectomy is not recommended because of the high incidence of metastases even when prostatic disease is still small, because of the high operative mortality, and because of the undesirable after-effects. Orchidectomy was performed in patients in whom the prostatic capsule had been invaded, or who had distant metastases. Estrogen therapy for prostatic carcinoma gives excellent results, and is very easy for both patient and physician.
  28. ^ a b c d e f g Tunn UW (1987). "Antiandrogene in der Therapie des fortgeschrittenen Prostatakarzinoms" [Antiandrogens in the Treatment of Advanced Prostate Cancer]. Konservative Therapie des Prostatakarzinoms [Conservative Therapy of Prostate Cancer] (in German). pp. 113–121. doi:10.1007/978-3-642-72613-2_12. ISBN 978-3-540-17724-1.
  29. ^ a b c d e f g Saborowski KJ (1988), Konservative Therapie mit Cyproteronacetat und Estradiolundecylat beim Fortgeschrittenen Prostatacarcinom: Eine 5-Jahres-Studie [Conservative Therapy with Cyproterone Acetate and Estradiol Undecylate in Advanced Prostate Cancer: A 5-Year Study] (in German), Bochum, Univ., Diss., OCLC 917571781, OL 24895092W
  30. ^ Mollard P (March 1963). "[Clinical action of estradiol undecylate in the treatment of prostatic cancer]" [Clinical action of estradiol undecylate in the treatment of prostatic cancer]. Lyon Medical (in French). 209: 759–765. PMID 13935867.
  31. ^ Schubert GE, Ziegler H, Völter D (1973). "[Comparison of histological and cytological studies of the prostate with special reference to oestrogene induced changes (author's transl)]" [Comparison of histological and cytological studies of the prostate with special reference to oestrogene induced changes]. Verhandlungen der Deutschen Gesellschaft Fur Pathologie (in German). 57: 315–318. PMID 4142204.
  32. ^ a b Satoskar RS, Bhandarkar SD, Rege NN (1973). Pharmacology and Pharmacotherapeutics. Popular Prakashan. pp. 934–. ISBN 978-81-7991-527-1.
  33. ^ a b Morgan HG, Morgan MH (1984). Aids to Psychiatry. Churchill Livingstone. p. 75. ISBN 978-0-443-02613-3. Treatment of sexual offenders. Hormone therapy. [...] Oestrogens may cause breast hypertrophy, testicular atrophy, osteoporosis (oral ethinyl oestradiol 0.01-0.05 mg/day causes least nausea). Depot preparation: oestradiol [undecyleate] 50-100mg once every 3–4 weeks. Benperidol or butyrophenone and the antiandrogen cyproterone acetate also used.
  34. ^ a b c Kennedy BJ (April 1967). "Effect of massive doses of estradiol undecylate in advanced breast cancer". Cancer Chemother Rep. 51 (2): 491–495.
  35. ^ a b c d e f Asscheman H, Gooren LJ, Assies J, Smits JP, de Slegte R (June 1988). "Prolactin levels and pituitary enlargement in hormone-treated male-to-female transsexuals". Clinical Endocrinology. 28 (6): 583–588. doi:10.1111/j.1365-2265.1988.tb03849.x. PMID 2978262. S2CID 29214187.
  36. ^ a b Asscheman H, Gooren LJ, Eklund PL (September 1989). "Mortality and morbidity in transsexual patients with cross-gender hormone treatment". Metabolism. 38 (9): 869–873. doi:10.1016/0026-0495(89)90233-3. PMID 2528051.
  37. ^ a b Gazzeri R, Galarza M, Gazzeri G (December 2007). "Growth of a meningioma in a transsexual patient after estrogen-progestin therapy". The New England Journal of Medicine. 357 (23): 2411–2412. doi:10.1056/NEJMc071938. PMID 18057351.
  38. ^ a b c Sweetman SC, ed. (2009). "Sex hormones and their modulators". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 2098. ISBN 978-0-85369-840-1.
  39. ^ a b c 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.
  40. ^ Lauritzen C, Studd JW (22 June 2005). Current Management of the Menopause. CRC Press. pp. 95–98, 488. ISBN 978-0-203-48612-2.
  41. ^ 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.
  42. ^ 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. ISBN 978-94-011-6167-1.
  43. ^ a b c d e f g h i j k Jacobi GH (June 1982). "Intramuscular cyproterone acetate treatment for advanced prostatic carcinoma: results of the first multicentric randomized trial". In Schröder FH (ed.). Proceedings Androgens and Anti-androgens, International Symposium, Utrecht, June 5th, 1982. Schering Nederland BV. pp. 161–169. ISBN 978-9090004327. OCLC 11786945.
  44. ^ a b Tunn UW, Graff J, Senge T (June 1982). "Treatment of inoperable prostatic cancer with cyproterone acetate". In Schröder FH (ed.). Proceedings Androgens and Anti-androgens, International Symposium, Utrecht, June 5th, 1982. Schering Nederland BV. pp. 149–159. ISBN 978-9090004327. OCLC 11786945.
  45. ^ a b c d e f g h i j Tunn UW, Radlmaier A, Neumann F (1988). "Antiandrogens in Cancer Treatment". In Stoll BA (ed.). Endocrine Management of Cancer: Contemporary Therapy. pp. 43–56. doi:10.1159/000415355. ISBN 978-3-8055-4686-7.
  46. ^ a b c d e f g Schröder FH, Radlmaier A (2009). "Steroidal Antiandrogens". In Jordan VC, Furr BJ (eds.). Hormone Therapy in Breast and Prostate Cancer. Humana Press. pp. 325–346. doi:10.1007/978-1-59259-152-7_15. ISBN 978-1-60761-471-5.
  47. ^ a b c d e f Ackermann R, Altwein JE, Faul P (13 March 2013). Aktuelle Therapie des Prostatakarzinoms. Springer-Verlag. pp. 276–277. ISBN 978-3-642-84264-1.
  48. ^ a b c d Namer M (October 1988). "Clinical applications of antiandrogens". Journal of Steroid Biochemistry. 31 (4B): 719–729. doi:10.1016/0022-4731(88)90023-4. PMID 2462132.
  49. ^ a b c d e Jacobi GR, Tunn UW, Senge TH (1 December 1982). "Clinical experience with cyproterone acetate for palliation of inoperable prostate cancer". In Jacobi GH, Hohenfellner R (eds.). Prostate Cancer. Williams & Wilkins. pp. 305–319. ISBN 978-0-683-04354-9.
  50. ^ Altwein JE, Jacobi GH, Hohenfellner R (1978). "Estrogen versus cyproterone acetate in untreated inoperable carcinoma of the prostate: first results of an open, prospective, randomized study". Abstracts 3rd Congress of the European Association of Urology, Monte Carlo.
  51. ^ a b c d e Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (1983). "Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension". Pulmonary Circulation. 10 (1): 40–48. doi:10.1007/BF00326861. PMC 7052475. PMID 32166015. S2CID 23447326.
  52. ^ Jacobi GH, Wenderoth UK (1982). "Gonadotropin-releasing hormone analogues for prostate cancer: untoward side effects of high-dose regimens acquire a therapeutical dimension". European Urology. 8 (3): 129–134. doi:10.1159/000473499. PMID 6281023.
  53. ^ Ockrim J, Lalani EN, Abel P (October 2006). "Therapy Insight: parenteral estrogen treatment for prostate cancer--a new dawn for an old therapy". Nature Clinical Practice. Oncology. 3 (10): 552–563. doi:10.1038/ncponc0602. PMID 17019433. S2CID 6847203.
  54. ^ Lycette JL, Bland LB, Garzotto M, Beer TM (December 2006). "Parenteral estrogens for prostate cancer: can a new route of administration overcome old toxicities?". Clinical Genitourinary Cancer. 5 (3): 198–205. doi:10.3816/CGC.2006.n.037. PMID 17239273.
  55. ^ Russell N, Cheung A, Grossmann M (August 2017). "Estradiol for the mitigation of adverse effects of androgen deprivation therapy". Endocrine-Related Cancer. 24 (8): R297–R313. doi:10.1530/ERC-17-0153. PMID 28667081.
  56. ^ Langley RE, Cafferty FH, Alhasso AA, Rosen SD, Sundaram SK, Freeman SC, et al. (April 2013). "Cardiovascular outcomes in patients with locally advanced and metastatic prostate cancer treated with luteinising-hormone-releasing-hormone agonists or transdermal oestrogen: the randomised, phase 2 MRC PATCH trial (PR09)". The Lancet. Oncology. 14 (4): 306–316. doi:10.1016/S1470-2045(13)70025-1. PMC 3620898. PMID 23465742.
  57. ^ Langley RE, Gilbert DC, Duong T, Clarke NW, Nankivell M, Rosen SD, et al. (February 2021). "Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme" (PDF). Lancet. 397 (10274): 581–591. doi:10.1016/S0140-6736(21)00100-8. PMID 33581820. S2CID 231885186.
  58. ^ Tunn UW, Senge T, Jacobi GH (1983). "Erfahrungen mit Cyproteronacetat als Monotherapie beim Inoperablen Prostatakarzinom" [Experience with Cyproterone Acetate as Monotherapy for Inoperable Prostate Cancer]. In Klosterhalfen H (ed.). Therapie des Fortgeschrittenen Prostatakarzinoms. Vortragsveranstaltung fur Urologen, Berlin 1982/83 [Therapy of Advanced Prostate Cancer. Lecture Event for Urologists, Berlin 1982/83]. Wiss Buchreihe, Schering AG. pp. 67–76. ISBN 978-3921817162. OCLC 67592679.
  59. ^ Schröder FH (1996). "Cyproterone Acetate — Results of Clinical Trials and Indications for Use in Human Prostate Cancer". Antiandrogens in Prostate Cancer. pp. 45–51. doi:10.1007/978-3-642-45745-6_4. ISBN 978-3-642-45747-0.
  60. ^ a b Schulze C (January 1988). "Response of the human testis to long-term estrogen treatment: morphology of Sertoli cells, Leydig cells and spermatogonial stem cells". Cell and Tissue Research. 251 (1): 31–43. doi:10.1007/BF00215444. PMID 3342442. S2CID 22847105.
  61. ^ a b c d e f g Vermeulen A (1975). "Longacting steroid preparations". Acta Clinica Belgica. 30 (1): 48–55. doi:10.1080/17843286.1975.11716973. PMID 1231448.
  62. ^ 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.
  63. ^ Schürmeyer T, Graff J, Senge T, Nieschlag E (March 1986). "Effect of oestrogen or cyproterone acetate treatment on adrenocortical function in prostate carcinoma patients". Acta Endocrinologica. 111 (3): 360–367. doi:10.1530/acta.0.1110360. PMID 2421511.
  64. ^ Spona J, Lunglmayr G (July 1980). "Prolaktin-Serumspiegel unter Behandlung des Prostatakarzinoms mit Östradiol-17 beta-undezylat und Cyproteronazetat". Verhandlungsbericht der Deutschen Gesellschaft für Urologie [Serum Prolactin Levels During Therapy of Prostatic Cancer with Estradiol-17 beta-undecylate and Cyproterone Acetate]. Wien. Klin. Wochenschr. Verhandlungsbericht der Deutschen Gesellschaft für Urologie (in German). Vol. 92. pp. 494–7. doi:10.1007/978-3-642-81706-9_120. ISBN 978-3-540-11017-0. PMID 6933738.
  65. ^ a b c d e f Jacobi GH, Altwein JE (1979). "Bromocriptin als Palliativtherapie beim fortgeschrittenen Prostatakarzinom:Experimentelles und klinisches Profil eines Medikamentes" [Bromocriptine as Palliative Therapy in Advanced Prostate Cancer: Experimental and Clinical Profile of a Drug]. Urologia Internationalis. 34 (4): 266–290. doi:10.1159/000280272. PMID 89747.
  66. ^ a b c d e Derra C (1981). Hormonprofile unter Östrogen-und Antiandrogentherapie bei Patienten mit Prostatakarzinom: Östradiolundecylat versus Cyproteronacetat [Hormone profiles under estrogen and antiandrogen therapy in patients with prostate cancer: estradiol undecylate versus cyproterone acetate] (Ph.D. thesis). Mainz, Universiẗat. OCLC 65055508. OL 24894194W.
  67. ^ Schulze H, Senge T (1987). Konservative Therapie des Prostatakarzinoms. pp. 89–98. doi:10.1007/978-3-642-72613-2_8. ISBN 978-3-540-17724-1.
  68. ^ a b Neumann F, El Etreby MF, Habenicht U, Radlmaier A, Bormacher K (1987). Options for androgen withdrawal and total blockage. pp. 61–86. doi:10.1007/978-3-642-72613-2_6. ISBN 978-3-540-17724-1.
  69. ^ Tunn UW, Senge T, Neumann F (1981). "Serumkonzentrationen von Testosteron und Prolaktin nach operativer und medikamentöser Kastration — eine Langzeitstudie bei Prostatakarzinom-Patienten". Verhandlungsbericht der Deutschen Gesellschaft für Urologie [Serum concentrations of testosterone and prolactin after surgical and medical castration-A long-term study in prostate cancer patients]. Verhandlungsbericht der Deutschen Gesellschaft für Urologie. Vol. 32. pp. 419–421. doi:10.1007/978-3-642-81706-9_123. ISBN 978-3-540-11017-0.
  70. ^ Baba S, Janetschek G, Wenderoth U, Jacobi GH (1981). "Beeinflussung des intraprostatischen Testosteron-Stoffwechsels durch Cyproteronazetat und Östradiolundecylat bei Patienten mit Prostatakarzinom: In vivo-Untersuchungen". Verhandlungsbericht der Deutschen Gesellschaft für Urologie [Influence of intraprostatic testosterone metabolism by cyproterone acetate and estradiol undecylate in patients with prostate cancer: in vivo studies]. Verhandlungsbericht der Deutschen Gesellschaft für Urologie. Vol. 32. pp. 464–466. doi:10.1007/978-3-642-81706-9_138. ISBN 978-3-540-11017-0.
  71. ^ Jacobi GH, Altwein JE (1980). "Testosterone plasma kinetics in patients with prostatic carcinoma treated with estradiol undecylate, cyproterone acetate and estramustine phosphate: a preliminary report". Steroid receptors, metabolism and prostatic cancer: proceedings of a workshop of the Society of Urologic Oncology and Endocrinology, Amsterdam, 27-28 April, 1979. Vol. 494. Excerpta Medica. pp. 144–151.
  72. ^ Nagel R, Schillinger E, Kölln CP, Pochhammer K (1973). 24. Tagung vom 13. Bis 16. September 1972 in Hannover [The behavior of serum lipids in patients with prostate cancer after treatment with estradiol undecylate]. Verhandlungsbericht der Deutschen Gesellschaft für Urologie. Vol. 24. pp. 298–301. doi:10.1007/978-3-642-80738-1_75. ISBN 978-3-540-06186-1.
  73. ^ Taupitz A, Otaguro K (1959). "Quantitative Examination of Serum Components After Antiandrogenic Therapy Against Prostatic Cancer" [Quantitative Examination of Serum Components after Antiandrogenic Therapy Against Prostatic Cancer: Clinical and Experimental Observation]. The Japanese Journal of Urology. 50 (3): 153–162. doi:10.5980/jpnjurol1928.50.3_153.
  74. ^ Götz H, Ehrmeier H (June 1971). "[Estrogens and ceruloplasmine level]" [Estrogens and ceruloplasmin levels]. Archiv Fur Gynakologie. 211 (1): 204–206. doi:10.1007/BF00682878. PMID 5108847. S2CID 38378905.
  75. ^ a b Vermeulen A (1977). "Transport and distribution of androgens at different ages". In Martini L, Motta M (eds.). Androgens and Antiandrogens. New York: Raven Press. pp. 53–65. ISBN 9780890041413. OCLC 925036459. In postmenopausal women, however, estrogen administration does not change the androgen levels significantly. The increase in TeBG capacity after injection of 100 mg Progynon Depot® (estradiol undecylate), therefore, is unequivocally the result of the estrogens: 6 days after injection, when plasma estradiol levels varied between 30 ng/100 ml [300 pg/mL] and 60 ng/100 ml [600 pg/mL], TeBG levels were nearly doubled (1.4–1.6 ✕ 107 M), whereas the free testosterone fraction decreased from 1.25% to 0.70%.
  76. ^ Saleh FM (11 February 2009). Sex Offenders: Identification, Risk Assessment, Treatment, and Legal Issues. Oxford University Press, USA. pp. 176–. ISBN 978-0-19-517704-6.
  77. ^ Salam MA (2003). Principles & Practice of Urology: A Comprehensive Text. Universal-Publishers. pp. 684–. ISBN 978-1-58112-412-5.
  78. ^ Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA (25 August 2011). Campbell-Walsh Urology: Expert Consult Premium Edition: Enhanced Online Features and Print, 4-Volume Set. Elsevier Health Sciences. pp. 2938–. ISBN 978-1-4160-6911-9.
  79. ^ Kjeld JM, Puah CM, Kaufman B, Loizou S, Vlotides J, Gwee HM, et al. (November 1979). "Effects of norgestrel and ethinyloestradiol ingestion on serum levels of sex hormones and gonadotrophins in men". Clinical Endocrinology. 11 (5): 497–504. doi:10.1111/j.1365-2265.1979.tb03102.x. PMID 519881. S2CID 5836155.
  80. ^ a b c d Vermeulen A (1975). "Longacting steroid preparations". Acta Clinica Belgica. 30 (1): 48–55. doi:10.1080/17843286.1975.11716973. PMID 1231448.
  81. ^ a b c Leyendecker G, Geppert G, Nocke W, Ufer J (May 1975). "[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)]" [Estradiol 17β, estrone, LH and FSH in serum after administration of estradiol 17β, estradiol benzoate, estradiol valeriate and estradiol undecylate in the female]. Geburtshilfe und Frauenheilkunde (in German). 35 (5): 370–374. PMID 1150068. 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.
  82. ^ a b c d e f g Geppert G (1975). 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]. pp. 1–34. OCLC 632312599.
  83. ^ a b Zimmermann W, Buescher HK, Taupitz A, Thewalt K (1964). "Steroidhormonausscheidung bei Patienten mit Erkrankungen der Prostata Unter Behandlung mit Natürlichen und Synthetischen Oestrogenen" [Steroid Hormone Excretion of Patients with Diseases of the Prostate under Treatment with Natural and Synthetic Estrogens]. Acta Endocrinologica (in German). 45 (4 Suppl 90): SUPPL90:211–SUPPL90:225. doi:10.1530/acta.0.045S211. PMID 14111328.
  84. ^ 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.
  85. ^ a b c Brotherton J (1976). Sex Hormone Pharmacology. Academic Press. pp. 226, 476. ISBN 978-0-12-137250-7.
  86. ^ a b Jucker E (8 March 2013). Fortschritte der Arzneimittelforschung / Progress in Drug Research / Progrès des recherches pharmaceutiques. Birkhäuser. pp. 243–. ISBN 978-3-0348-7044-3. 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).
  87. ^ a b c d e f Toppozada M (June 1977). "The clinical use of monthly injectable contraceptive preparations". Obstetrical & Gynecological Survey. 32 (6): 335–347. doi:10.1097/00006254-197706000-00001. PMID 865726.
  88. ^ Kuhl H, Taubert HD (July 1973). "A new class of long-acting hormonal steroid preparation: synthesis of oligomeric estradiol derivatives". Steroids. 22 (1): 73–87. doi:10.1016/0039-128X(73)90072-X. PMID 4737545.
  89. ^ Kuhl H, Taubert HD (September 1973). "[Proceedings: New type of long-acting steroids: Synthesis and biological effect]" [A New Type of Long-Acting Steroid Preparation: Synthesis and Biological Efficacy]. Archiv Fur Gynakologie. 214 (1): 127–128. doi:10.1007/BF00671087. PMID 4801412. S2CID 26261148.
  90. ^ Kuhl H, Auerhammer W, Taubert HD (October 1976). "Oligomeric oestradiol esters: a new class of long-acting oestrogens". Acta Endocrinologica. 83 (2): 439–448. doi:10.1530/acta.0.0830439. PMID 989671.
  91. ^ a b Kicovic PM, Luisi M, Franchi F, Alicicco E (July 1977). "Effects of orally administered oestradiol decanoate on plasma oestradiol, oestrone and gonadotrophin levels, vaginal cytology, cervical mucus and endometrium in ovariectomized women". Clinical Endocrinology. 7 (1): 73–77. doi:10.1111/j.1365-2265.1977.tb02941.x. PMID 880735. S2CID 13639429.
  92. ^ a b Luisi M, Kicovic PM, Alicicco E, Franchi F (April 1978). "Effects of estradiol decanoate in ovariectomized women". Journal of Endocrinological Investigation. 1 (2): 101–106. doi:10.1007/BF03350355. PMID 755846. S2CID 38187367.
  93. ^ a b Chaudhury RR (1 January 1981). Pharmacology of Estrogens. Elsevier Science & Technology Books. p. 36. ISBN 978-0-08-026869-9.
  94. ^ Jameson JL, De Groot LJ (25 February 2015). Endocrinology: Adult and Pediatric E-Book. Elsevier Health Sciences. pp. 2387–. ISBN 978-0-323-32195-2.
  95. ^ Nieschlag E, Behre HM (6 December 2012). Testosterone: Action - Deficiency - Substitution. Springer Science & Business Media. pp. 300–. ISBN 978-3-642-72185-4.
  96. ^ a b c d e f Leyendecker G, Geppert G, Nocke W, Ufer J (May 1975). "[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)]" [Estradiol 17β, estrone, LH and FSH in serum after administration of estradiol 17β, estradiol benzoate, estradiol valeriate and estradiol undecylate in the female]. Geburtshilfe und Frauenheilkunde (in German). 35 (5): 370–374. PMID 1150068.
  97. ^ Burdock GA (1997). Encyclopedia of Food and Color Additives. CRC Press. pp. 2870–. ISBN 978-0-8493-9412-6.
  98. ^ Junkmann K (1957). "Long-acting steroids in reproduction". Recent Progress in Hormone Research. 13: 389–419, discussion 419–28. PMID 13477813.
  99. ^ Junkmann K, Witzel H (1957). "[Chemistry and pharmacology of steroid hormone esters]" [Chemistry and pharmacology of steroid hormone esters]. Zeitschrift Fur Vitamin-, Hormon- und Fermentforschung (in German). 9 (1–2): 97–143 contd. PMID 13531579.
  100. ^ Armstrong NA, James KC (1980). "Drug release from lipid-based dosage forms. I". International Journal of Pharmaceutics. 6 (3–4): 185–193. doi:10.1016/0378-5173(80)90103-9.
  101. ^ Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (1953). "Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension" [Over protracted effective estrogens]. Pulmonary Circulation (in German). 10 (1). doi:10.1007/BF00246561. PMC 7052475. PMID 32166015. S2CID 20753905.
  102. ^ "17-undecenoate of estradiol".
  103. ^ Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (1967). "Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension". Pulmonary Circulation. 10 (1): 107–127. doi:10.1080/00224496709550519. PMC 7052475. PMID 32166015.
  104. ^ von Bruchhausen F, Dannhardt G, Ebel S, Frahm AW, Hackenthal E, Holzgrabe U (2 July 2013). Hagers Handbuch der Pharmazeutischen Praxis: Band 8: Stoffe E-O. Springer-Verlag. pp. 84–. ISBN 978-3-642-57994-3.
  105. ^ Boschann HW (July 1958). "Observations of the role of progestational agents in human gynecologic disorders and pregnancy complications". Annals of the New York Academy of Sciences. 71 (5): 727–752. Bibcode:1958NYASA..71..727B. doi:10.1111/j.1749-6632.1958.tb46803.x. PMID 13583829.
  106. ^ Bishop PM (1962). Chemistry of the Sex Hormones. Thomas. p. 78.
  107. ^ a b el-Mahgoub S, Karim M (February 1972). "Depot estrogen as a monthly contraceptive in nulliparous women with mild uterine hypoplasia". American Journal of Obstetrics and Gynecology. 112 (4): 575–576. doi:10.1016/0002-9378(72)90319-5. PMID 5008627.
  108. ^ a b Toppozada MK (1983). "Monthly Injectable Contraceptives". In Goldsmith A, Toppozada M (eds.). Long-Acting Contraception. pp. 93–103. OCLC 35018604.
  109. ^ 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.
  110. ^ Kadam SS (July 2007). Principles of Medicinal Chemistry Volume 2. Pragati Books Pvt. Ltd. pp. 381–. ISBN 978-81-85790-03-9.
  111. ^ Beck LR, Cowsar DR, Pope VZ (July 1980). "Long-acting steroidal contraceptive systems" (PDF). Research Frontiers in Fertility Regulation. 1 (1): 1–16. PMID 12179628. S2CID 13863575.
  112. ^ Karim M, el-Mahgoub S (July 1971). "Conception control by cyclic injections of norethisterone enanthate and estradiol unducelate". American Journal of Obstetrics and Gynecology. 110 (5): 740–742. doi:10.1016/0002-9378(71)90268-7. PMID 5563241.

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