Estriol

288.38100

288.38

200-022-2

FB33469R8E

12169

DTXSID9022366

Leaflets from alcohol|Very small monoclinic crystals from dilute alcohol|White, microcrystalline powder

QG03CA04|G03CA04|G - Genito urinary system and sex hormones

29072990

60.69000

2.58000

Solid

1.27 g/cm³

282 °C

469ºC at 760 mmHg

220.8ºC

1.624

In water, 27.34 mg/L at 25 deg C (est)

-20ºC Freezer

9.93X10-12 mm Hg at 25 deg C (est)

LD50 oral in rat: > 2gm/kg

Specific optical rotation at D (sodium) line: +58 deg, +/-5 deg (0.04 g in 1 mL dioxane)

Odorless

Henry's Law constant = 1.33X10-12 atm-cu m/mol at 25 °C (est)

pKa = 10.54 (est)

During heating on the microscope heating stage, rearrangement of the crystal structure takes place at 270 °C and 275 °C (rate of heating 4 °C/min, Kofler microscope heating stage).|Precipitated by digitonin|Crystals from 90% alcohol, mp 126 °C /Estriol triacetate/

NONH for all modes of transport

3

R60

53-22-36/37/39-45-36/37

KG8225000

T

P201-P281-P308 + P313

H351-H360

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

|Danger|H350 (30.77%): May cause cancer [Danger Carcinogenicity]|P201, P202, P260, P263, P264, P270, P273, P281, P308+P313, P314, P391, P405, and P501|Aggregated GHS information provided by 169 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The concentration of estriol in typical raw sewage ranges from 0.01-0.20 ug/L(1). Concentrations in 30 sewage treatment plant effluents sampled in Italy, 10/99-03/2000, ranged from 0.43 to 18 ng/L (1.3 ng/L median)(2). Estriol was detected at concentrations of <1.0 (July 2003), 2.9 (Sept 2003, and <1.0 ng/L (Feb 2004) in effluent from the Eysines Sewage Treatment Plant (northern suburbs, Bordeaux, France) and runs through agricultural and residential areas(3). Estriol was present at concentrations of 261 and 263 ng/L in influent samples to the Piera and Igualada sewage treatment plants, respectively, on the Anoia tributary in the vicinity of Barcelona, Spain, sampled from April to June, 1999; it was not detected in the effluent detected (method detection limits = 2-100 ng/L)(4).|Estriol was not detected in a typical dairy waste disposal system for 2000 dairy cows in San Jacinto, CA; samples include fresh manure less than 2 hrs old, piled manure at 2 weeks, and 3 lagoon dams at 3 months(1). The mean estriol concentration in a swine wastewater manure pit was 1,475 pM(2).

SEDIMENT: Levels of estriol in sediment from the Beitang River, Dagu River, and Yongding New River in the Tianjin area, northern China, sampled in June 2007 were not detected-6.99, not detected-7.29, and not detected-3.77 ng/g dry weight, respectively, with mean concentrations of 3.08, 2.61 and 1.97 ng/g dry weight, respectively(1).

ORAL (LD50): Acute: >2000 mg/kg [Rat].

/AQUATIC SPECIES/ Gonadal intersex and high prevalences of the female phenotype have been observed in fish populations in urbanized areas. Environmental estrogens discharged in sewage treatment plant effluents may be responsible for feminization of fish but many compounds with the potential to induce these responses occur in effluents, including natural and synthetic estrogen hormones, degradation products of alkylphenol ethoxylate surfactants, and plasticizers. In this study, the estrogen hormones 17a-ethinylestradiol, 17beta-estradiol, estrone, and estriol induced intersex (i.e., testis-ova) and altered sex in Japanese medaka (Oryzias latipes) when these fish were exposed to nanogram per liter concentrations of test compounds from hatch to approximately 100 days after hatch. ...

In patients with hypertriglyceridemia, estrogen therapy may be associated with further increases in plasma triglycerides resulting in pancreatitis and other complications. If acute pancreatitis occurs, estrogens should be discontinued. The risk of gallbladder disease appears to be increased 2- to 4-fold in postmenopausal women receiving estrogen replacement therapy. In one study, an increased risk of gallbladder disease occurred after 2 years of use of the drugs and doubled after 4 or 5 years of use. In another study, an increased risk of gallbladder disease was apparent between 6-12 months of use. /Estrogen General Statement/|Gynest Cream contains arachis oil (peanut oil) and should not be applied by patients known to be allergic to peanuts. As there is a possible relationship between allergy to peanuts and allergy to soya, patients with soya allergy should also avoid Gynest Cream.|Mental depression may occur in patients receiving estrogens. In a few women receiving estrogen-containing oral contraceptives, mental depression was severe and led to suicidal behavior. Patients with a history of mental depression should be observed carefully and estrogens discontinued if severe depression recurs during use. /Estrogen General Statement/|Estrogens have been reported to produce keratoconus (steepening of corneal curvature) and intolerance to contact lenses. Contact lens wearers who develop visual disturbances or changes in lens tolerance during estrogen therapy should be assessed by an ophthalmologist; temporary or permanent cessation of contact lens wear should be considered. Although neuro-ocular lesions such as optic neuritis or retinal thrombosis have been associated with use of estrogen-containing oral contraceptives, these lesions have not been reported to date with estrogens. If unexplained, sudden or gradual, partial or complete loss of vision; proptosis or diplopia; papilledema; or retinal vascular lesions occur during therapy with an estrogen, the drug should be discontinued and appropriate diagnostic and therapeutic measures instituted. /Estrogen General Statement/|Estrogens may exacerbate asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions. /Estrogen General Statement/

Estriol is a metabolite of the hormone estradiol and is usually the predominant estrogenic metabolite found in urine. During pregnancy the placenta produces relatively large amounts of estriol(1).

Estriol's production and use as an estrogen in human and veterinary medicine(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1,200(SRC), determined from a structure estimation method(2), indicates that estriol is expected to have moderate mobility in soil(SRC). Volatilization of estriol from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.3X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Estriol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). Biodegradation data in soil were not available(SRC, 2011).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1,200(SRC), determined from a structure estimation method(2), indicates that estriol is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.3X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 19(SRC), from its log Kow of 2.45(6) and a regression-derived equation(7), and an estimated BCF of 50(8) suggest the potential for bioconcentration in aquatic organisms is low to moderate(SRC). Biodegradation data in water were not available(SRC, 2011).|AQUATIC FATE: The mean estriol concentration in a swine wastewater manure pit was 1,475 pico Moles; the concentration was 32 pico Moles in the associated primary anaerobic lagoon. The concentration dropped to 15 pico Moles following subsequent residence in open constructed wetland ponds(1).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), estriol, which has an estimated vapor pressure of 9.9X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase estriol may be removed from the air by wet or dry deposition(SRC). Estriol irradiated with a xenon arc lamp exhibited a photodegradation half-life of 2.9 hours in river water and 38.2 hours in air-saturated purified water(4), and therefore may be susceptible to direct photolysis by sunlight(SRC).

Estriol is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Estriol absorbs light at wavelengths of 280 nm(2), and therefore may be susceptible to direct photolysis by sunlight(SRC). Estriol irradiated with a xenon arc lamp exhibited a photodegradation half-life of 2.9 hours in river water and 38.2 hours in air-saturated purified water(3).

An estimated BCF of 19 was calculated in fish for estriol(SRC), using a log Kow of 2.45(1) and a regression-derived equation(2). An estimated BCF of 50 was calculated in fish for estriol using a food-web model(3). According to a classification scheme(4), these BCF estimates suggest the potential for bioconcentration in aquatic organisms is low to moderate(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of estriol can be estimated to be 1,200(SRC). According to a classification scheme(2), this estimated Koc value suggests that estriol is expected to have low mobility in soil. A Freundlich adsorption coefficient, log Kd, of 1.33 has been measured(3). The compound was not detected in the effluent of a 23-day column drainage study using Mahall-Laveen sandy loam soil from an area northwest of Phoenix, AZ and 200 L of treated effluent from a municipal waste treatment facility; reporting limit = 0.005 ug/L(4), suggesting adsorption to soil in the column(SRC).

The Henry's Law constant for estriol is estimated as 1.3X10-12 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that estriol is expected to be essentially nonvolatile from water and moist soil surfaces(2). Estriol is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.9X10-12 mm Hg(SRC), determined from a fragment constant method(3).

SURFACE WATER: Estriol concentrations were reported at a 21.4% frequency with a maximum concentration of 0.051 ug/L and median 0.019 ug/L, in 70 of 139 U.S. streams sampled from 1999-2000 as part of the USGS National Reconnaissance Study(1). Estriol was reported in 20% of 5 samples with a concentration range of <0.005 to a max of 0.02 ug/L of unspecified surface waters from the Great Lakes Basin(2). The compound was tested for but not detected in the Eleven Point and North Fork of the White Rivers in Missouri, sampled from August 2003 through November 2004(3). The estriol concentration in Tiber River water, Italy, was reported as 0.11 ng/L(4). Levels of estriol in water from the Beitang River, Dagu River, and Yongding New River in the Tianjin area, northern China, sampled in June 2007 were not detected-15.44, 2.26-46.4, and not detected-10.8 ng/L, respectively, with mean concentrations of 10.3, 12.4 and 5.76 ng/L, respectively(5). Estriol was detected in river water samples from the Jalle d'Eysines which receives effluent from the Eysines Sewage Treatment Plant (northern suburbs, Bordeaux, France) and runs through agricultural and residential areas. Approximately 33% of its flow is accountable to the sewage treatment plant. Mean downstream concentrations were 1.5, 0.3, and 0 ng/L at 1, 2, and 4 km distant, respectively, from outflow on September 23, 2003; it was not detected 2 km upstream(6).

ENVIRONMENTAL: Free natural estrogens in raw and commercial whole milk were quantitated by radioimmunoassay. The concentration range of estriol was 9 to 31 pg/mL. Equilibrium dialysis of skim milk with hydrogen 3-labeled estrogens showed that 61 to 66% of estriol was protein bound. Whey proteins demonstrated a greater binding capacity than casein. This result was confirmed by radioimmunoassay of dry curd cottage cheese and whey. The concentration in curd was 6 pg/g and in whey 3 pg/mL. ... Butter was highest with a concentration of 87 pg/g. Human colostrum demonstrated a maximum concentration of 4 to 5 ng/mL for estriol. By the 5th day postpartum, it decreased to become similar to cow's milk.

NIOSH (NOES Survey 1981-1983) has statistically estimated that 3,694 workers (2,675 of these were female) were potentially exposed to estrone in the US(1). Occupational exposure to estriol may occur through inhalation and dermal contact with this compound at workplaces where estriol is produced or used. Exposure to estriol via ingestion will occur when administered drugs containing this compound. Monitoring data indicate that the general population may be exposed to estriol at well below the therapeutic dose via ingestion of drinking water(SRC).

... Human colostrum demonstrated a maximum concentration of 4 to 5 ng/mL for estriol. By the 5th day postpartum, it decreased to become similar to cow's milk.

Used as a test to determine the general health of an unborn fetus.|The treatment of hormone-dependent urinary incontinence due to sphincter mechanism incompetence in ovariohysterectomised bitches.

/Estriol is indicated as/ hormone replacement therapy for treatment of atrophic vaginitis and kraurosis in post-menopausal women.|/Estriol is indicated for the/ treatment of pruritus vulvae and dyspareunia associated with atrophic vaginal epithelium.

Gynest Cream is not indicated during pregnancy. If pregnancy occurs during use of Gynest Cream, treatment should be withdrawn immediately.|Gynest Cream contains arachis oil (peanut oil) and should not be applied by patients known to be allergic to peanuts. As there is a possible relationship between allergy to peanuts and allergy to soya, patients with soya allergy should also avoid Gynest Cream.|Before initiating or re-instituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contra-indications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman. Women should be advised what changes in their breasts should be reported to their doctor or nurse. Investigations, including mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.|The risk of endometrial hyperplasia and carcinoma is increased when systemic estrogens are administered alone for prolonged periods of time. The endometrial safety of long-term or repeated use of topical vaginal estrogens is uncertain. Therefore, if repeated, treatment should be reviewed at least annually, with a special consideration given to any symptoms of endometrial hyperplasia or carcinoma.|For more Drug Warnings (Complete) data for ESTRIOL (40 total), please visit the HSDB record page.

Estriol (also oestriol) is one of the three main estrogens produced by the human body. It is only produced in significant amounts during pregnancy as it is made by the placenta. In pregnant women with multiple sclerosis (MS), estriol reduces the disease's symptoms noticeably, according to researchers at UCLA's Geffen Medical School.

Estriol is readily absorbed following intravaginal application. Peak serum estriol concentrations are generally observed within 2 hours following intravaginal application and remain elevated for 6 hours.|Systemic bioavailability on vaginal administration is better than after oral administration. Intravaginal application of 1 mg estriol in women with senile atrophy of the vaginal epithelium results in serum levels similar to those seen after oral administration of 10 mg estriol.|Plasma estriol levels increased from <90pmol/L (26 pg/mL) about fifty fold over a few hours after intravaginal administration of Gynest Cream. Eight to ten hours after administration, 50% of women still had estriol levels above 90pmol/L (26 pg/mL).|Estriol circulates with the blood, about 14% free, 8% bound to SHBG and the rest bound to albumin.|More than 95% of estriol is excreted in the urine, predominantly in the form of glucuronides.

Primary metabolites of estriol include the 16-alpha-glucuronide, 3-glucuronide, 3-sulfate and 3-sulfate 16-alpha-glucuronide.|The metabolic disposition of estrogens includes oxidative metabolism (largely hydroxylation) and conjugative metabolism by glucuronidation, sulfonation and/or O-methylation. Estradiol is converted to estrone by a 17beta-hydroxysteroid dehydrogenase; the estrone produced is further metabolized to 16alpha-hydroxyoestrone and then to estriol.|Estriol is a common metabolite of estrone and estradiol-17-beta in animals and in humans. Estriol is excreted in humans as conjugated and unconjugated 2-hydroxy estriol after 2-hydroxylation.

Estriol levels can be measured to give an indication of the general health of the fetus. DHEA-S is produced by the adrenal cortex of the fetus. This is converted to estriol by the placenta. If levels of "unconjugated estriol" are abnormally low in a pregnant woman, this may indicate a problem with the development of the child. The drug interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estriol upon the target cell. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.|... Synthetic estriol, is chemically and biologically identical to endogenous human estriol. Estriol, a weak estrogen, is a natural metabolite of estradiol, the predominant estrogen. Estriol exerts estrogenicity by binding to estrogen receptors, present in the female genital tract. Estriol, oral or vaginal, similar to estradiol, corrects lowered proliferation and abnormal physiology in the atrophic vaginal epithelium seen in estrogen deficient states, such as after natural or surgical menopause. In contrast, the histology of the endometrium after using Gynest Cream rarely shows minor signs of proliferation in previously atrophic endometria.|Estrogens have an important role in the reproductive, skeletal, cardiovascular, and central nervous systems in women, and act principally by regulating gene expression. Biologic response is initiated when estrogen binds to a ligand-binding domain of the estrogen receptor resulting in a conformational change that leads to gene transcription through specific estrogen response elements (ERE) of target gene promoters; subsequent activation or repression of the target gene is mediated through 2 distinct transactivation domains (ie, AF-1 and AF-2) of the receptor. The estrogen receptor also mediates gene transcription using different response elements (ie, AP-1) and other signal pathways. Recent advances in the molecular pharmacology of estrogen and estrogen receptors have resulted in the development of selective estrogen receptor modulators (eg, clomiphene, raloxifene, tamoxifen, toremifene), agents that bind and activate the estrogen receptor but that exhibit tissue-specific effects distinct from estrogen. Tissue-specific estrogen-agonist or -antagonist activity of these drugs appears to be related to structural differences in their estrogen receptor complex (eg, specifically the surface topography of AF-2 for raloxifene) compared with the estrogen (estradiol)-estrogen receptor complex. A second estrogen receptor also has been identified, and existence of at least 2 estrogen receptors (ER-alpha, ER-beta) may contribute to the tissue-specific activity of selective modulators. While the role of the estrogen receptor in bone, cardiovascular tissue, and the CNS continues to be studied, emerging evidence indicates that the mechanism of action of estrogen receptors in these tissues differs from the manner in which estrogen receptors function in reproductive tissue. /Estrogen General Statement/|Intracellular cytosol-binding proteins for estrogens have been identified in estrogen-responsive tissues including the female genital organs, breasts, pituitary, and hypothalamus. The estrogen-binding protein complex (ie, cytosol-binding protein and estrogen) distributes into the cell nucleus where it stimulates DNA, RNA, and protein synthesis. The presence of these receptor proteins is responsible for the palliative response to estrogen therapy in women with metastatic carcinoma of the breast. /Estrogen General Statement/|Estrogens have generally favorable effects on blood cholesterol and phospholipid concentrations. Estrogens reduce LDL-cholesterol and increase HDL-cholesterol concentrations in a dose-related manner. The decrease in LDL-cholesterol concentrations associated with estrogen therapy appears to result from increased LDL catabolism, while the increase in triglyceride concentrations is caused by increased production of large, triglyceride-rich, very-low-density lipoproteins (VLDLs); changes in serum HDL-cholesterol concentrations appear to result principally from an increase in the cholesterol and apolipoprotein A-1 content of HDL2- and a slight increase in HDL3-cholesterol. /Estrogen General Statement/|For more Mechanism of Action (Complete) data for ESTRIOL (12 total), please visit the HSDB record page.

Reported impurities include: estradiol, estra-1,3,5(10),9(11)-tetraene-3,16alpha,17beta-triol (9,11-didehydroestriol), estra-1,3,5(10)-triene-3,16alpha,17beta-triol (17-epi-estriol), estra-1,3,5(10)-triene-3,16beta,17beta-triol (16-epi-estriol), estra-1,3,5(10)-triene-3,16beta,17alpha-triol (16,17-epi-estriol), 3-hydroxyestra-1,3,5(10)-trien-17-one (estrone); 3,16alpha-dihydroxyestra- 1,3,5(10)-trien-17-one, 3-hydroxy-17-oxa-D-homoestra-1,3,5(10)-trien-17a-one and 3-methoxyestra-1,3,5(10)-triene-16alpha,17beta-diol (estriol 3-methyl ether).

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ In order to study the biological effects of estriol in women 20 mg estriol was administered daily to 7 young women. Plasma luteinizing hormone (LH), estradiol (E2), progesterone (Pg) and prolactin (Prl) were measured during a treatment and a control cycle every second or third day. Further 3, 6 or 20 mg estriol was administered in a single dose to 5 women and plasma Prl, unconjugated and conjugated estriol (E3) measured over 24 hr at 2-3 intervals. In 2 experiments with 20 mg E3, blood samples were taken more frequently, over 6 hr. When 20 mg E2 was administered daily, 2 of the 7 young women had anovulatory cycles. The mean plasma E2 was lower during the follicular and ovulatory phases (P less than 0.025) and mean plasma LH was higher (P less than 0.005) during the luteal phase, when E3 was given. Because of the 2 anovulatory cycles the mean Pg value during the luteal phase was lower (P less than 0.05) during treatment. There was a slight decrease in mean Prl in 5 out of 6 women (P less than 0.0005), but in only 1 woman was this decrease substantial (from a mean value of 27.6-18.9 ng/mL; P less than 0.01). When 6 or 20 mg E3 was administered orally in the morning a significant negative correlation (P less than 0.01) between plasma Prl and unconjugated E3 was found. The correlation coefficient was highest (r = -0.74) with 6 mg E3. When 3 mg was administered no obvious effect on Prl section was seen. However, when results from all experiments with identical time schedules were pooled (two with 3 mg, two with 6 mg and one with 20 mg E3) and the mean values for plasma Prl calculated and compared with the mean values obtained in 7 control experiments, it was found that E3 administration in the morning almost abolishes the Prl rise during the following night. There was a statistically significant (P less than 0.0125) decrease in the difference between the maximum value during the night and the minimum value during the day. The minimum value was significantly higher (P less than 0.01) and the maximum value significantly lower (P less than 0.025) after E3 treatment, compared to the control values. It is concluded that long-term administration of 20 mg E3 usually has only a slight but significant decreasing effect on mean plasma Prl concentration measured in the morning, before the next dose is taken.|/SIGNS AND SYMPTOMS/ Symptoms of overdose of estrogen therapy may include breast pain or tenderness, nausea, break-through bleeding, abdominal cramps and/or bloating. Vaginal lavage should be considered.|/EPIDEMIOLOGY STUDIES/ Several studies have shown an increased relative risk of endometrial carcinoma in postmenopausal women who received prolonged estrogen replacement therapy for relief of menopausal symptoms. This risk was independent of other known risk factors for endometrial carcinoma and appeared to depend on duration and dosage of estrogen therapy. While there appears to be no increased risk of endometrial carcinoma in postmenopausal women receiving estrogen therapy for less than 1 year, prolonged estrogen therapy may be associated with an increased risk of such carcinoma. The risk of endometrial carcinoma reportedly is increased 2- to 12-fold in postmenopausal women receiving unopposed estrogen therapy compared with those not receiving estrogens; such increased risk may depend on dosage and duration of therapy and may be 15- to 24-fold higher in women receiving long-term (5 years or more) estrogen therapy. Limited data indicate that a substantial increased risk of endometrial carcinoma may persist for up to 15 years following discontinuance of estrogen therapy. Because of the increased risk of endometrial carcinoma associated with prolonged estrogen therapy, patients receiving prolonged treatment with the drugs should be evaluated at least twice yearly to reassess the need for continued therapy. Results of several studies indicate that when progestins are used concomitantly with estrogen replacement therapy, the incidence of endometrial hyperplasia and endometrial carcinoma is reduced substantially. In a randomized, controlled, multicenter study in postmenopausal women, endometrial hyperplasia occurred in 20 or 1% or less of women receiving estrogen therapy alone or in conjunction with progestins, respectively. In the WHI study, the incidence of endometrial carcinoma in women receiving hormone replacement therapy (conjugated estrogens 0.625 mg in conjunction with medroxyprogesterone acetate 2.5 mg daily) was similar to the incidence in women receiving placebo. /Estrogen General Statement/|/EPIDEMIOLOGY STUDIES/ The estrogen/progestin arm of the WHI study recently was terminated prematurely because of an increased incidence of breast cancer in women receiving HRT. In the WHI study, the risk of invasive breast cancer was 26% higher in women receiving HRT (conjugated estrogens 0.625 mg in conjunction with medroxyprogesterone acetate 2.5 mg daily) compared with those receiving placebo; the estimated hazard ratio for breast cancer was 1.26. While there have been several observational studies evaluating the risk of breast cancer in women receiving HRT, conclusions are limited by healthy-user bias; variations in specific preparations, dosage, and duration of therapy; and differences in the methods used to determine breast cancer end points. In aggregate, breast cancer incidence is slightly increased among current (relative risk: 1.21-1.4) or long-term (longer than 5 years) recipients (relative risk: 1.23-1.35) compared with nonusers. Based on these findings, recommendations on the appropriate use of hormone therapy have been revised. Because the risks of hormone therapy exceed the benefits for the prevention of chronic diseases in postmenopausal women, experts state that ERT or HRT should not be used for the prevention of chronic conditions in postmenopausal women. The American Heart Association (AHA), the American College of Obstetricians and Gynecologists (ACOG), US Food and Drug Administration (FDA), and manufacturers recommend that hormone therapy not be used to prevent heart disease in healthy women (primary prevention) or to protect women with preexisting heart disease (secondary prevention). ACOG, FDA, and the manufacturers also recommend that women receiving hormone therapy solely for the prevention of postmenopausal osteoporosis consider alternative therapy (eg, alendronate, raloxifene, risedronate). /Estrogen General Statement/|For more Human Toxicity Excerpts (Complete) data for ESTRIOL (20 total), please visit the HSDB record page.

(16alpha,17beta)-Estra-1,3,5(10)-Triene-3,16,17-Triol

Estriol is commercially available as tablets, pessaries and a cream.

Carcinogen

Liquid Chromatography: estriol can be detected amperometrically in the reductive mode.|Analyte: estriol; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: estriol; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards|Analyte: estriol; matrix: chemical purity; procedure: dissolution in alcohol; liquid chromatography with ultraviolet detection at 281 nm and comparison to standards

An estriol test system is a device intended to measure estriol, an estrogenic steroid, in plasma, serum, and urine of pregnant females. Estriol measurements are used in the diagnosis and treatment of fetoplacental distress in certain cases of high-risk pregnancy.|As estrogens (total, in pregnancy) test system is a device intended to measure total estrogens in plasma, serum, and urine during pregnancy. The device primarily measures estrone plus estradiol. Measurements of total estrogens are used to aid in the diagnosis and treatment of fetoplacental distress in certain cases of high-risk pregnancy.|As estrogens (total, nonpregnancy) test system is a device intended to measure the level of estrogens (total estrone, estradiol, and estriol) in plasma, serum, and urine of males and nonpregnant females. Measurement of estrogens (total, nonpregnancy) is used in the diagnosis and treatment of numerous disorders, including infertility, amenorrhea (absence of menses) differentiation of primary and secondary ovarian malfunction, estrogen secreting testicular and ovarian tumors, and precocious puberty in females.

Veterinary drugs -> Incurin -> EMA Drug Category|Sex hormones and modulators of the genital system -> Veterinary pharmacotherapeutic group|Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients|Lipids -> Sterol Lipids [ST] -> Steroids [ST02] -> C18 steroids (estrogens) and derivatives [ST0201]