Estrogens, conjugated

370.4

370.085083

235-199-5

7XY8FW3E68

DTXSID00872961

91.88000

3.95170

Solid

254.5°C

Commercially available conjugated estrogens USP tablets, synthetic conjugated estrogens A tablets, synthetic conjugated estrogens B tablets, and conjugated estrogens USP vaginal cream should be stored at controlled room temperature (20-25 °C). Conjugated estrogens USP powder for injection should be stored at a temperature of 2-8 °C prior to reconstitution. Following reconstitution, solutions of the drug should be used immediately.

UN3077 Environmentally hazardous substances, solid, n.o.s., Hazard class: 9; Labels: 9-Miscellaneous hazardous material, Technical Name Required. UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials. PGIII.

Avoid exposure to heat, air, and moisture; any exposure will cause equilin content to lose potency

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.|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.

The injectable /formulation/ is physically and/or chemically incompatible with protein hydrolysate, ascorbic acid, or any solution with an acid pH. Specialized references should be consulted for specific compatibility information.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including estrogens, conjugated, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Estrogens, Steroidal are listed as known to be human carcinogens. /Estrogens, Steroidal/[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s084ster.pdf]

|Danger|H315 (97.67%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P261, P264, P271, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 43 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H350 (70.37%): May cause cancer [Danger Carcinogenicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 54 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

The literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent. Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Effluents have been shown to contain several compounds with estrogenic properties. These include natural estrogens and synthetic estrogens widely used in birth-control pills. Women are the primary sources of these estrogenic compounds and during sewage treatment, these conjugates are transformed into the parent and biologically-active compounds(3).|Daily Estrogenic Compounds Excretion by Humans, 2000(1).|Estradiol equivalent concentrations in influents and effluents of sewage treatment plants located along the Yeongsan and Seomijin Rivers in Korea were investigated. The treatment processes of Korean STPs were sufficient to reduce estrogenic activity of municipal wastewater. Surface water samples from Laos, Cambodia, Vietnam, China, Indonesia, Thailand and Malaysia showed higher estradiol equivalent concentrations in comparison to that reported in European countries, America, and Japan(1). Land application of animal manures results in endocrine-disrupting compounds such as estrogenic compounds being released to the environment, posing a threat to aquatic and wildlife species. Surface runoff of estrogenic compounds can be much lower from soils amended with pelletized poultry litter than the raw form of litter(2).|Estrogenic compounds present in animal manure(1).

While early formulations of OCCs were associated with frequent serum enzyme elevations, current formulations and hormonal replacement therapy have not been linked to ALT or alkaline phosphatase elevations at rates any higher than occur with placebo. Estrogens and OCCs can cause mild inhibition of bilirubin excretion, leading to jaundice in patients with inherited forms of bilirubin metabolism such as the Dubin Johnson syndrome. More importantly, estrogens and OCCs can induce a clinically apparent cholestatic liver injury which typically arises during the first few cycles of therapy, and rarely after the six months (Case 1). The onset is typically insidious with fatigue and pruritus, followed by nausea, dark urine and jaundice. Serum enzyme elevations are usually mixed or cholestatic, although very early during the injury, ALT levels can be markedly elevated (5- to 20-fold). The characteristic pattern, however, is bland intrahepatic cholestasis and liver biopsy shows little inflammation or hepatocyte necrosis. Resolution may be delayed (Case 2), but estrogens have not been definitely linked to chronic injury, vanishing bile duct syndrome or acute liver failure. Women with OCC induced cholestasis often have a history of idiopathic cholestasis of pregnancy and there is likely a genetic component, most commonly with variants in the bile salt export pump (BSEP, ABC B11). Estrogens and particularly combinations of estrogens and progestins have been linked to episodes of marked serum aminotransferase elevations without symptoms, jaundice or cholestasis. The abnormalities resolve quickly with stopping the hormonal treatment. This syndrome may be more frequent with progestins than with estrogens alone.

Metabolism of estrogen is mediated in part by cytochrome P-450 (CYP) isoenzyme 3A4, and the possibility exists that drugs that induce or inhibit this isoenzyme may affect plasma estrogen concentrations. Concomitant use of estrogens with drugs that induce CYP3A4 (eg, carbamazepine, phenobarbital, rifampin, St. John's wort [Hypericum perforatum]) may result in decreased plasma concentrations of estrogen, resulting in decreased therapeutic effects and/or changes in uterine bleeding profile. /Estrogen General Statement/|Concomitant use of estrogen with drugs or foods that inhibit CYP3A4 (eg, clarithromycin, erythromycin, grapefruit juice, itraconazole, ketoconazole) may result in increased plasma concentrations of estrogens and an increase in the incidence of adverse effects. /Estrogen General Statement/|Rifampin reportedly decreases estrogenic activity during concomitant use with estrogens. This effect has been attributed to enhanced metabolism of estrogen, presumably by induction of hepatic microsomal enzymes. /Estrogen General Statement/|Estrogens have been reported to enhance the anti-inflammatory effect of hydrocortisone in patients with chronic inflammatory skin diseases. It has been suggested that estrogens may decrease the hepatic metabolism of corticosteroids and/or alter serum corticosteroid protein binding. Patients receiving concomitant estrogen and corticosteroid therapy should be observed for signs of excessive corticosteroid effects... /Estrogen General Statement/

LD50 Rat intraperitoneal 325 mg/kg

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/|Cholestasis is manifested by the development of malaise, anorexia, and pruritus about 2 weeks to 2 months after the start of therapy. Occasionally, arthralgia, fever, and rash may occur. Serum bilirubin may range from 3-10 mg/dL and is mostly conjugated. Women with a history of jaundice during pregnancy have an increased risk of jaundice recurrence while receiving estrogen-containing oral contraceptives. If jaundice occurs during estrogen therapy, the drug should be discontinued. Estrogens may precipitate hepatic forms of porphyria, and the drugs probably should not be used by women who have a familial history of hepatic porphyrias, since the occurrence of these conditions appears to be genetically determined. Steroid hormones (including estrogens) may be poorly metabolized in patients with hepatic dysfunction; therefore, estrogens should be administered with caution to these individuals. /Estrogen General Statement/

Estrogens are a group of naturally occurring steroid sex hormones which are characterized by their ability to induce estrus in the female mammal(1). Estrogenic activity is not restricted to the estrogenic sex hormones. Certain plant constituents, bituminous components of the Seefeld oil shale, easily synthesized stilbene derivatives, and their dihydro compounds have estrogenic properties(2).

Since 1930 synthesized steroid hormone analogues have been developed with improved therapeutic properties for the control of pituitary function, for substitution therapy in deficiency syndromes such as hypogonadism or after the menopause, and particularly for the control of ovulation (contraceptive steroids). Estrogenic hormones are used in substitution therapy to control estrogen deficiency caused by ovarian hypofunction, castration, or menopause. They are also used in suppression therapy to suppress gonadotropin-induced ovulation and the endogenous production of estrogens. Because of the latter, estrogens are used together with gestagens as combination contraceptive agents(1). These applications may result in their release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values ranging from 420(2) to 18,000(3) indicate that estrogenic substances are expected to have moderate to no mobility in soil(SRC). Volatilization of estrogenic substance from moist soil surfaces is not expected to be an important fate process(SRC) given estimated Henry's Law constants of >2.0X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Estrogenic substances are not expected to volatilize from dry soil surfaces(SRC) based upon estimated vapor pressures of >1.0X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Bacteria present in wastewater are capable of completely biodegrading natural estrogenic compounds(2). The synthetic estrogen ethinylestradiol has been classified as not readily biodegradable using a sewage treatment plant study(6).|AQUATIC FATE: Based on a classification scheme(1), Koc values ranging from 420(2) to 18,000(3) indicate that estrogenic substances are expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(SRC) based upon estimated Henry's Law constants of >2.0X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), estimated BCF values of 19-110(SRC), from measured log Kow values(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low to high, provided the compounds are not metabolized by organisms(SRC). Bacteria present in wastewater are capable of completely biodegrading natural estrogenic compounds(2). The synthetic estrogen ethinylestradiol has been classified as not readily biodegradable using a sewage treatment plant study(8).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), estrogenic substances, which have estimated vapor pressures of >1.0X10-9mm Hg at 25 °C(SRC), determined from a fragment constant method(2), are expected to exist solely in the particulate phase. Particulate-phase estrogenic substances may be removed from the air by wet or dry deposition(SRC). Estriol absorbs light at wavelengths 280 nm(3). Estrone irradiated with a xenon arc lamp exhibited a photodegradation half-life of 2-3 hours in river water and 4.7 hours in air-saturated purified water(4). Therefore, estrogenic substances may be susceptible to direct photolysis by sunlight(SRC).

Estrogenic substances are 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 280 nm(2). Estrone irradiated with a xenon arc lamp exhibited a photodegradation half-life of 2-3 hours in river water and 4.7 hours in air-saturated purified water(3). Therefore, estrogenic subtances may be susceptible to direct photolysis by sunlight(SRC).

Estimated BCF of 19-110 were calculated in fish for various estrogenic substances(SRC), using measured log Kow values(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF range suggests the potential for bioconcentration in aquatic organisms is low to high(SRC), provided the compounds are not metabolized by the organism(SRC).

The Koc of estrogenic substances generally fall into the range of 420(1) to 18,000(2). According to a classification scheme(3), this Koc range suggests that estrogenic substances are expected to have moderate to no mobility in soil. Natural estrogens are mainly removed from the aqueous phase by adsorption onto solids such as sludge in wastewater or soil in cases of land application(1). In soils with a long history of treatment with manure, biosolids, or wastewater, sorption of estrogenic substances may be dependent on soil organic carbon content(4).

The estimated Henry's Law constants for estrogenic substances were generally >2.0X10-11 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that estrogenic substances are expected to be essentially nonvolatile from water and moist soil surfaces(2). Estrogenic substances are not expected to volatilize from dry soil surfaces(SRC) based upon estimated vapor pressures of >1.0X10-9 mm Hg(SRC), determined from a fragment constant method(3).

DRINKING WATER: Estrogenic compounds concentration in source and drinking water(1). [Table#4410]

Average phytoestrogen levels in foods purchased in Cambridgeshire, Great Britain (detection limit = 1.5 ug/100 g dry weight)(1).|For more Food Survey Values (Complete) data for ESTROGENIC SUBSTANCES, CONJUGATED (7 total), please visit the HSDB record page.

Average phytoestrogen levels in foods purchased in Cambridgeshire, Great Britain (detection limit = 1.5 ug/100 g dry weight)(1).

Occupational exposure to estrogenic substances may occur through inhalation and dermal contact with this compound at workplaces where estrogenic substance is produced or used. Monitoring data indicate that the general population may be exposed to estrogenic substances via ingestion of some plants, ingestion of and dermal contact with contaminated water. Exposure to estrogenic substances among the general female population may be furthered to those administered the medicinals containing these substances. (SRC)

Estrogens and oral contraceptives are both associated with several liver related complications including intrahepatic cholestasis, sinusoidal dilatation, peliosis hepatis, hepatic adenomas, hepatocellular carcinoma, hepatic venous thrombosis and an increased risk of gallstones. These side effects are more common with higher doses of estrogens, as were used in the early high dose estrogen formulation of oral contraceptives, but they have also been described with use of more modern birth control pills and with low dose, estrogen hormonal replacement therapy.

Hormones and Synthetic Substitutes:

Estrogens|Conjugated estrogen therapy is indicated in the treatment of moderate to severe vasomotor symptoms due to menopause. /Included in US product label/|Conjugated estrogen therapy is indicated in the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered. /Included in US product label/|Conjugated estrogen therapy is indicated in the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. /Included in US product label/|For more Therapeutic Uses (Complete) data for ESTROGENIC SUBSTANCES, CONJUGATED (12 total), please visit the HSDB record page.

ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER: Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is no evidence that the use of "natural" estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses.|CARDIOVASCULAR AND OTHER RISKS: Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. The estrogen alone substudy of the Women's Health Initiative (WHI) reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 6.8 years and 7.1 years, respectively, of treatment with oral conjugated estrogens (CE 0.625 mg) alone per day, relative to placebo.|The estrogen-plus-progestin substudy of the Women's Health Initiative reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) per day, relative to placebo.|The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI study, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with CE 0.625 mg alone and during 4 years of treatment with CE 0.625 mg combined with MPA 2.5 mg, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.|For more Drug Warnings (Complete) data for ESTROGENIC SUBSTANCES, CONJUGATED (40 total), please visit the HSDB record page.

Following oral administration, the natural, unconjugated estrogens are inactivated in the GI tract and liver. Conjugated estrogens and some synthetic derivatives of the natural estrogens may be administered orally. Absorption and metabolism following oral administration of these drugs is rapid and daily doses are usually required. /Estrogen General Statement/|Synthetic conjugated estrogens are soluble in water and are well absorbed from the gastrointestinal tract after release from the drug formulation. The Synthetic conjugated estrogens tablet releases the synthetic conjugated estrogens slowly over a period of several hours.|Estrogens are readily absorbed through the skin and mucous membranes. Depending on the amount of estrogen applied, systemic as well as local effects may occur following topical application. /Estrogen General Statement/|The pharmacokinetics of PREMARIN 0.45 mg and 1.25 mg tablets were assessed following a single dose with a high-fat breakfast and with fasting administration. The Cmax and AUC of estrogens were altered approximately 3-13%. The changes to Cmax and AUC are not considered clinically meaningful.|For more Absorption, Distribution and Excretion (Complete) data for ESTROGENIC SUBSTANCES, CONJUGATED (19 total), please visit the HSDB record page.

Exogenous estrogens are metabolized in the same manner as endogenous estrogens. Circulating estrogens exist in a dynamic equilibrium of metabolic interconversions. These transformations take place mainly in the liver. Estradiol is converted reversibly to estrone, and both can be converted to estriol, which is the major urinary metabolite. Estrogens also undergo enterohepatic recirculation via sulfate and glucuronide conjugation in the liver, biliary secretion of conjugates into the intestine, and hydrolysis in the gut followed by reabsorption. In postmenopausal women a significant portion of the circulating estrogens exist as sulfate conjugates, especially estrone sulfate, which serves as a circulating reservoir for the formation of more active estrogens.|The steroidal estrogens are metabolized principally in the liver, although the kidneys, gonads, and muscle tissues may be involved to some extent. The steroids and their metabolites are conjugated at the hydroxyl group of the C 3 position with sulfuric or glucuronic acid; these conjugates may undergo further metabolic change. Conjugation increases water solubility and facilitates excretion in urine. Large amounts of free estrogens are also distributed into the bile, reabsorbed from the GI tract, and recirculated through the liver where further degradation occurs. /Estrogen General Statement/|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. Hydroxylation of estradiol at the 2 position is a major metabolic pathway in the liver. There are large inter-individual differences in estradiol 2-hydroxylation in human liver samples, which may be reflected by differences in estrogenic action. 4-Hydroxylation of estradiol to a catechol is a minor pathway (usually < 15% of 2-hydroxylation) in the liver.|Estrone sulfate is the estrogen found at the highest concentration in plasma and seems to constitute a storage form for circulating estrogens. Estrone sulfate can be hydrolysed to estrone by arylsulfatases, which are widely distributed in human tissues.|Conjugated equine estrogens are hydrolysed to their active form in the gastrointestinal tract and also undergo considerable hepatic metabolism before entering the bloodstream in an active form. Most sulfate esters are hydrolysed to free or unconjugated estrogen by enzymes in the lower gut; the free estrogen is absorbed by intestinal tissue, where it can be reconjugated with sulfate. Therefore, the estrogen sulfate found in the bloodstream is not the same sulfate that was administered. The rate of dissolution is important because it influences where the active ingredients of the product are released in the gastrointestinal tract, a factor which may affect the amounts of the estrogen that are activated and the patterns of active and inactive metabolites. Equilin and equilenin are interconverted to 17beta-dihydroequilin and 17beta-dihydroequilenin and correspond to the interrelation between estrone and estradiol. As in the case of natural estrogen in women, there is an equilibrium between equilin, equilenin and their metabolites and the respective sulfates.

The mean (SD) apparent terminal elimination half-life of conjugated estrone is 14 (+/- 6) hours and conjugated equilin is 11 (+/- 6) hours. /Synthetic conjugated estrogens, B/

The principal pharmacologic effects of conjugated estrogens are similar to those of other natural and synthetic estrogens.|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 ESTROGENIC SUBSTANCES, CONJUGATED (7 total), please visit the HSDB record page.

/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/ Postmenopausal conjugated equine estrogens (CEE) therapies increase the risk of cognitive impairment in women aged 65 years or older and are associated with smaller regional brain volumes; however, the link between these two phenomena has not been established. Standardized magnetic resonance imaging was performed on 1,403 women, 1-4 years after they had participated in randomized placebo-controlled clinical trials of CEE-based therapies. Women included in this report were aged 65-80 years and free of dementia and mild cognitive impairment (MCI) when originally enrolled in the trials, which lasted an average of 4-6 years and were conducted at 14 academic U.S. medical centers. The associations that regional brain volumes and ischemic lesion volumes had with the development of cognitive impairment (ie, dementia or MCI) were contrasted between treatment groups using analyses of covariance. Fifty-three women developed MCI or probable dementia during follow-up. Among women who had been prescribed CEE-based therapies, cognitive impairment was associated with relatively smaller hippocampal (p = 0.0002) and total brain volumes (p = 0.03). Qualitatively, these associations appeared to be independent of their level of pretreatment cognitive function. Among women who had been prescribed placebo, these relationships were not evident; instead, cognitive impairment was associated with greater ischemic lesion volume in the frontal lobe (p = 0.007) and overall (p = 0.02). A mechanism by which CEE-based postmenopausal hormone therapy induces cognitive impairment appears to be through increased brain atrophy.|/HUMAN EXPOSURE STUDIES/ ... A rise in cholesterol saturation of hepatic bile was observed after giving conjugated equine estrogens (0.5 mg/kg) to 7 fasting patients with indwelling T-tubes. Liver function tests were normal and bile culture was negative. One mL of hepatic bile was collected aft er 6, 12, and 24 hours for lipid determinations. The administration of estrogens promptly produced lithogenic hepatic bile. The effect was transient with the lithogenic index returning to normal at 24 hours. 3 days previous to this investigation hepatic bile had been normal. ...|/SIGNS AND SYMPTOMS/ Acute overdosage of large doses of oral contraceptives in children reportedly produces almost no toxicity except nausea and vomiting. Acute overdosage of estrogens may cause nausea, and withdrawal bleeding may occur in females. /Estrogen General Statement/|/CASE REPORTS/ To report a case of fatal pulmonary embolism associated with the use of iv estrogen therapy for menometrorrhagia. A 52-year-old woman with fibroid uterus treated with GnRH analogues with add-back therapy who presented with excessive vaginal bleeding. Intravenous conjugated estrogens were administered for a total of six doses. A fatal thromboembolic event /occurred/. The day after iv conjugated estrogens were administered, the patient had only scant vaginal bleeding, but she experienced the sudden onset of respiratory distress, became comatose, and subsequently had ventricular fibrillation leading to asystole. All resuscitative efforts failed. Postmortem examination revealed bilateral pulmonary artery thromboembolism (saddle embolus). Intravenous conjugated estrogen therapy may be complicated by fatal thromboembolic events. This potential adverse effect must be considered in the use of such therapy for severe menometrorrhagia, especially when treating a patient at increased risk.|For more Human Toxicity Excerpts (Complete) data for ESTROGENIC SUBSTANCES, CONJUGATED (26 total), please visit the HSDB record page.

Conjugated estrogens tablets, USP for oral administration contains a mixture of conjugated estrogens obtained exclusively from natural sources, occurring as the sodium salts of water-soluble estrogen sulfates blended to represent the average composition of material derived from pregnant mares' urine. It is a mixture of sodium estrone sulfate and sodium equilin sulfate. It contains as concomitant components, as sodium sulfate conjugates, 17alpha-dihydroequilin, 17alpha-estradiol, and 17beta-dihydroequilin.|Synthetic conjugated estrogens A tablets contain a blend of nine (9) synthetic estrogenic substances. The estrogenic substances are sodium estrone sulfate, sodium equilin sulfate, sodium 17alpha-dihydroequilin sulfate, sodium 17alpha-estradiol sulfate, sodium 17beta-dihydroequilin sulfate, sodium 17alpha-dihydroequilenin sulfate, sodium 17beta-dihydroequilenin sulfate, sodium equilenin sulfate and sodium 17beta-estradiol sulfate.|Synthetic conjugated estrogens B tablets contain a blend of ten (10) synthetic estrogenic substances. The estrogenic substances are: sodium estrone sulfate, sodium equilin sulfate, sodium 17alpha-dihydroequilin sulfate, sodium 17alpha-estradiol sulfate, sodium 17beta-dihydroequilin sulfate, sodium 17alpha-dihydroequilenin sulfate, sodium 17beta-dihydroequilenin sulfate, sodium equilenin sulfate, sodium 17beta-estradiol sulfate, and sodium delta8,9-dehydroestrone sulfate.|CENESTIN tablets for oral administration, are available in 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg and 1.25 mg strengths of synthetic conjugated estrogens, A. Tablets also contain the following inactive ingredients: ethylcellulose, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polysorbate 80, pregelatinized starch, titanium dioxide, and triethyl citrate.|For more Formulations/Preparations (Complete) data for ESTROGENIC SUBSTANCES, CONJUGATED (6 total), please visit the HSDB record page.

The term "conjugated estrogens" refers to mixtures of at least eight compounds, including sodium estrone sulfate and sodium equilin sulfate, that are derived wholly or in part from equine urine, are plant-based or are manufactured synthetically from estrone and equilin. Conjugated estrogens contain as concomitant components the sodium sulfate conjugates of 17alpha-dihydroequilin, 17beta-dihydroequilin and 17alpha-estradiol.|Conjugated estrogens (natural) are a mixture that contains the sodium salts of the water soluble sulfate esters of estrone and equilin derived wholly or in part from equine urine or prepared synthetically from estrone and equilin. Conjugated estrogens (natural) also contain conjugated estrogenic substances of types that are excreted by pregnant mares and include delta8,9-dehydroestrone, 17alpha-dihydroequilenin, 17beta-dihydroequilenin, 17alpha-dihydroequilin, 17beta-dihydroequilin, equilenin, 17alpha-estradiol and 17beta-estradiol.|Conjugated estrogens (synthetic) are a mixture of conjugated estrogens that are prepared synthetically from plant sources (i.e. soy (Glycine Max) and yams (Dioscorea Mexicana)). Conjugated estrogens (synthetic) are commercially available as preparations that contain a mixture of nine of the 10 known conjugated estrogenic substances that are present in currently available commercial preparations of conjugated estrogens (natural). However, in contrast to currently available preparations of conjugated estrogens (natural), the conjugated estrogenic substances present in conjugated estrogens (synthetic) are prepared entirely synthetically.|In general, the pharmacological activity of synthetic gonadal steroids is never limited to interaction with a particular type of receptor (i.e., estrogenic, androgenic, progestagenic, glucocorticoid, or mineralocorticoid); instead, the spectrum of biological and pharmacological activities is dose-dependent. For example, some synthetic C-19 steroids have a high progestagenic potency, but frequently retain androgenic effects. The synthetic estrogen 17-ethinyl-estradiol displays high oral absorption due to its low metabolic inactivation and has become a major component of oral contraceptives.

Improved colorimetric method for analysis of conjugated estrogens.|GLC assay of conjugated estrogen formulations.|Estrogenic components were identified with gas chromatography and combined gas chromatography-mass spectrometry.|Gas chromatographic method for quantitative analysis of esterified estrogen tablet formulation and of estrogenic material present in pregnant mares' urine.|For more Analytic Laboratory Methods (Complete) data for ESTROGENIC SUBSTANCES, CONJUGATED (8 total), please visit the HSDB record page.

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.

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