Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of daily oral cyclical estrogen therapy on the plasma lipid and lipoprotein levels in postmenopausal women was determined. Included were 39 women with distressing postmenopausal vasomotor symptoms. Ethinyl estradiol (EE2) .05 mg was given to 20 women and estradiol valerinate (EV) to 19 others. The drugs were given as tablets once daily for 3-week cycles with 1-week intervals. After overnight fasts, blood samples were taken before and during treatment at 1, 3, and 6 months. During EV therapy, the HDL-TC and the HDL-phosphlipid concentrations increased 10-15% after 6 cycles. The net effect on the risk of development of ischemic cardiovascular disease due to the change in plasma lipids induced by EE2 is uncertain. The plasma lipid changes during EV therapy might possibly retard the development of atherosclerosis. However, the lipid metabolism of postmenopausal women may be different from that of fertile women.
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PMID:Metabolic and hormonal effects of post-menopausal oestrogen replacement treatment. II. Plasma lipids. 20 45

Ethinyl estradiol treatment to female rats resulted in increased levels of serum alkaline phosphatase, but was not associated with any other manifestation of toxicity such as increased serum transaminases or toxic lesions. Elevated serum alkaline phosphatase seen in rats treated with chloroform was associated with frank hepatotoxicity. Induction of hepatic drug metabolising enzymes in rats by phenobarbitone treatment did not result in raised serum alkaline phosphatase levels. Estradiol benzoate treatment to rats also did not increase serum alkaline phosphatase levels. Ethinyl estradiol also resulted in increased alkaline phosphatase content in the liver, intestine and bone. The raised intestinal alkaline phosphatase content of rats treated with phenobarbitone or estradiol benzoate was not associated with an increase in the serum levels. There was histochemical evidence of induction of canalicular alkaline phosphatase in the liver in Ethinyl Estradiol treatment. The study of the electrophoretic separation of serum alkaline phosphatase of ethinyl estradiol treated rats revealed the presence of a new fast moving fraction, similar to those seen in bile duct ligated rats. It is concluded that the serum alkaline phosphatase increase during ethinyl estradiol treatment at least in part is from the liver, due to new synthesis.
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PMID:Serum alkaline phosphatase elevation in female rats treated with ethinyl estradiol. 67 18

A sensitive and reliable radioimmunoassay (RIA) for measuring norethindrone (NET) in serum is described. Of a number of ring-A-reduced NET metabolites, only 2 cross-reacted appreciably in this RIA. Ethinyl estradiol and mestranol exhibited cross-reactions of only 1.1 and .4%, respectively. Serum concentrations of NET before and after ingestion of 4 NET-containing oral contraceptives (OCs) by 3 women each were measured by this RIA. In all 12 volunteers, serum NET levels rose rapidly after oral intake, reaching peak levels within .5-4 hours (median, 1.5) and fell precipitiously thereafter. Peak serum NET averaged 10.2 ng/ml after Ortho Novum 1/50 ingestion, 10.4 after Norinyl 1+50, 7.5 after Brevicon, and 4.3 after Micronor ingestion. Individual peak NET levels varied considerably in each group. Average half-lives varied from 2.3-4.4 hours, depending on OC compound ingested. After discontinuation of OCs, serum NET levels remained detectable ( .05 ng/ml) for at least 5 days in all 3 women who took Ortho Novum 1/50 but in none of the other subjects, suggesting that different preparations of identical doses and combinations of OCs may yield different serum NET profiles.
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PMID:A radioimmunoassay for norethindrone (NET): measurement of serum NET concentrations following ingestion of NET-containing oral contraceptive steroids. 75 Jan 88

The study included 69 women taking a desogestrel (n = 30)- or gestodene (n = 39)-containing low-dose combined oral contraceptive for at least 3 months. Group size was calculated to detect a difference in mean values of 80% of 1 standard deviation (alpha = 0.05, beta = 0.1). Seven serum samples were obtained up to 4 h, and 1 sample 24 h, after drug intake on 1 day between the 10th and the 21st day of the cycle. The concentrations of sex-hormone-binding globulin (SHBG), corticoid-binding globulin (CBG) and cortisol were measured in a 0- to 4-hour serum pool by radioimmunoassay. Ethinyl estradiol (EE2) levels were analyzed in single and pooled samples using anti-EE2-6 beta-carboxymethyloxime-bovine serum albumin antiserum. The area under the curves (AUC) up to 4 and 24 h and Cmax and tmax were evaluated. Statistical analysis (analysis of covariance) did not reveal a dependence of values on duration of treatment or day of cycle. Both treatments resulted in almost identical values for all parameters evaluated. The mean levels of SHBG, CBG and cortisol were in the range of 186-226 nmol/l, 89-93 mg/l and 280-281 micrograms/l, respectively. Mean maximum EE2 levels of 106-129 pg/ml were found 1.6-1.8 h after pill intake and AUC0-4 h accounted for 329-374 pg.h.ml-1. The recently reported differences in serum EE2 and CBG levels between two groups of 11 women each treated with desogestrel- and gestodene-containing pills, respectively, could not be confirmed.
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PMID:Comparison of serum ethinyl estradiol, sex-hormone-binding globulin, corticoid-binding globulin and cortisol levels in women using two low-dose combined oral contraceptives. 214 29

Mammary carcinomas have been induced by 3.5 Gy whole-body gamma radiation administered at age 40 to 50 days to virgin female Sprague-Dawley rats. In 142 irradiated controls carcinoma incidence averaged 7.8% in survivors observed less than 300 days and 38.3% of those surviving longer (P less than 0.001 by t test). Mammary cancer promotion was inhibited by two methods: estriol (E3) 638 micrograms/month (2.2 microns/mo) subcutaneously for natural life span begun 2 weeks after exposure reduced cancer incidence from 76% in controls to 48% after 331 to 449 mean days observation until neoplasia was palpable (P less than 0.02 by chi-square analysis). Uterine weights were similar in control and treated groups, and were 15% to 18% greater than uteri of nonirradiated controls from other simultaneous experiments. Six monthly 638-micrograms doses of 17 alpha ethinyl estriol (EE3) reduced tumors from 88% in controls to 64% (P less than 0.05 by chi-square analysis) and delayed cancer onset (P less than 0.01-0.04 by life table analysis). Ethinyl estradiol (EE2) after 6 months' treatment similarly delayed mammary tumor development reducing incidence to 75% (NS), with a six-fold increase in nonmammary epithelial malignant tumors. Estriol administration begun between 3 days before to 5 days after radiation did not alter mammary cancer incidence in six experiments. Monthly implantation of 2.5 mg tamoxifen (4.44 microns/mo) started 2 weeks after radiation reduced mammary cancer incidence from 83% to 14% after 307 to 314 days' observation (P less than 0.001 by chi-square analysis). Treated rats had atrophic ovaries and uteri consistent with blockade of endogenous estradiol activity. Short-term parenteral E3 or EE3 therapy using 10 to 30 micrograms/kg/day (35-100 microns/kg/day) rapidly differentiated virgin rat mammary glands without impairment of subsequent estrus cycles and offers an alternative to castration or life-long antiestrogen therapy for reduction of risk of radiogenic mammary carcinoma.
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PMID:Inhibition of radiogenic mammary carcinoma in rats by estriol or tamoxifen. 270 80

At this time 3 triphasics are widely used in the US: Ortho-Novum 7/7/7, Tri-Norinyl, and Triphasil. Ethinyl estradiol is the preferred estrogenic agent for the triphasic products. Torethindrone and levonorgestrel were chosen as the progestins for the triphasic products. It is the combined effects of estrogen and progestin in the triphasics that provide their contraceptive action. Triphasil increases both the estrogen and the progestin at midcycle; Tri-Norinyl and Ortho-Novum 7/7/7 elevate the progestin only. The midcycle surges of estrogen and luteinizing hormone are dampened, and ovulation is inhibited. The triphasics represent a 98.7% reduction in total steroid content since oral contraceptives (OCs) were introduced. An estrogen dose of 30-50 mcg will inhibit ovulation, and side effects with such a dose are considered tolerable. The triphasic OCs are in this range. An estrogen dose of 20 mcg has been tested but is slightly less effective and is not recommended. Contraceptive failures have occurred with the triphasic products. In 1486 women studied, 6 pregnancies have occurred. Of these failures, one may have been because of a drug interaction with a barbituate. 1 pregnancy was due to patient failure; 3 consecutive pills were missed. Only 2 pregnancies were certain drug failures. Because of the gentle suppression of ovarian function, it has been observed that the menstrual flow is less affected than by standard OCs. Due to the fact that less total steroid is delivered and more endometrial shedding occurs, it is hoped that the triphasic preparations will have less of a "lingering" effect on the return to functional fertility. Most of the published data on side effects is available from the UK, North America, and Europe on the formulation known in the US as Triphasil. Nausea, vomiting, breakthrough bleeding, weight gain, and breast tenderness appear to be the most common side effects. The major medical reasons for triphasic discontinuation include breast tenderness, weight gain, breakthrough bleeding, nausea and vomiting, headache, and increased bleeding during the 1 week of withdrawal. Rifampin and phenobarbital are examples of drugs found to decrease pill efficiency, including triphasics. Also, a triphasic may interfere with the action of another drug. The new triphasics are appropriate when starting new patients on OCs. Patient counseling is essential. Due to the low margin of error as a consequence of lesser suppression of ovarian function, the patient needs to be well instructed in how to take the pill and advised of the consequences of missed tables.
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PMID:The triphasics: insights for effective clinical use. 382 67

203 women 19-40 years of age were administered the gestagen preparations Volidan, Cyclofarlutal, Ovulen, Ciba AC-101, and Stediril as a contraceptive. 49 other women were administered these preparations as therapeutic and/or diagnostic measures in different gynecological complications. Side effects such as spotting, acylic bleeding, nausea, headaches and breast swelling were more frequent with the high-dose preparations such as Volidan and Cyclofarlutal. Intolerance to the preparation and subsequent discontinuation occurred only in a small percentage of the users. All of the preparations achieved 100% effectiveness as contraceptives. It is noted that these preparations were used with some success in treating dysmenorrhea, menometrorrhagia because of hyperplasia of the endometrium, and in severe climacteric syndromes. It has also been used as a pregnancy test. Constant medical control of the administration of these preparations is necessary both when they are used as contraceptives and as therapeutic measures, particularly in the case of young women.
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PMID:[Clinical aspects of the administration of gestagen preparations (Volidan, Cyclofarlutal, Ovulen, Ciba AC-101 and Steridil)]. 545 44

Glucose tolerance and plasma insulin concentrations were determined in intact female mice treated orally, subcutaneously and intramuscularly for 4 and 24 days with estradiol-17 beta (5 micrograms/kg/day), ethinyl estradiol (5 micrograms/kg/day) and progesterone (1 mg/kg/day). Estradiol-17 beta improved glucose tolerance and raised plasma insulin concentrations. These effects were generally greater after the longer treatment period and the s.c. administration route produced the greatest improvement in glucose tolerance with the smallest increase in plasma insulin. Ethinyl estradiol produced qualitatively similar effects to estradiol-17 beta, but quantitatively smaller. Progesterone raised plasma insulin concentrations after the longer treatment period, notably with oral and intramuscular administration, although glucose tolerance was not significantly altered. The results demonstrate the important influence of administration route and treatment duration on the changes in glucose homeostasis induced by sex steroids.
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PMID:Influence of administration route and treatment duration on the glucoregulatory effects of sex steroids in female mice. 639 10

Ethinyl estradiol sulfates are major circulating metabolites of ethinyl estradiol (EE2); this is a relationship analogous to that of endogenous estrone and estrone sulfate. Because of the wide use of contraceptives containing EE2, the pharmacokinetics of its sulfate conjugates are of some importance. In previous studies of the intermediate metabolism of ethinyl estrogens we have shown that the baboon is an appropriate animal model. Accordingly, oral and/or intravenous doses of EE2 or each of its three sulfates were administered to castrate female baboons, and plasma levels of EE2 and its sulfates were studied by specific radioimmunoassay or radioisotope counting. After intravenous administration of EE2, the 3-sulfate and the 3,17-disulfate are the major circulating metabolites. After oral dosage administration, the 3-glucuronide and, in some cases, the 3,17-diglucuronide also become important. After intravenous administration, about twice as much of the drug exists in the sulfate as in the free form, as reflected by the areas under the plasma level curves. The bioavailability of orally administered EE2 was about 60%, confirming the presence of a substantial first-pass effect. Hydrolysis at the 17-position occurs when EE2-17-sulfate is administered orally but appears not to occur with intravenous administration. EE2 and the three sulfates, given intravenously, exhibited two-compartment open-model kinetics. The elimination phase half-lives of all four compounds were similar, ranging from 8.8 to 11.2 hours. The area under the plasma level curve of EE2 resulting from the intravenous administration of the 3-sulfate was approximately 8% of the total area under the plasma level curve of both EE2 and EE2 sulfates. The ratio of the area under the plasma level curve of sulfates resulting from 3-sulfate administration compared to the other two sulfates was approximately 0.3, reflecting the existence of other metabolic pathways for its disposition.
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PMID:The pharmacokinetics and metabolism of ethinyl estradiol and its three sulfates in the baboon. 684 27

Prolonged estrogen treatment induced an enlargement of the anterior pituitary gland and finally resulted in irreversible pituitary tumours. Using continuous estrogen delivery [subcutaneous (s.c.) cholesterol-estrogen implants], the effects of ethinyl estradiol and the likewise synthetic estrogens STS 153 and STS 456 have been studied with or without concomitant administration of a progestogen without anti-estrogenic activities (STS 557). There was a dose-dependent prolactin cell-stimulating effect of all these estrogens. Ethinyl estradiol (EE2) had the most marked effect followed by STS 456 which coincides with the relative uterotrophic activity found in rats and mice. The elevated serum prolactin levels in rats with an EE2 implant for 6 months could be reduced slightly but not significantly by apomorphine and reserpine at a daily dose of 100 micrograms/animal and 5 micrograms/animal, respectively. Daily administration of 300 micrograms L-dopa led to a slight but insignificant increase of serum prolactin. The high pituitary weight and serum prolactin levels induced by long-term EE2 treatment were partially reversible after implant withdrawal.
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PMID:Induction of pituitary tumours and hyperprolactinemia in female rats by estrogens. The effect of apomorphine, reserpine and L-dopa. 693 73


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