Sample records for mestranol
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Body fluid volumes in rats with mestranol-induced hypertension
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fowler, W.L. Jr.; Johnson, J.A.; Kurz, K.D.
Because estrogens have been reported to produce sodium retention, this study investigated the possibility that hypertension in rats resulting from the ingestion of an estrogen used as an oral contraceptive could be due to increases in body fluid volumes. Female rats were given feed containing mestranol for 1, 3, and 6 mo; control rats were given the feed without mestranol. The mestranol-treated rats had higher arterial pressures than the controls only after 6 mo of treatment. Plasma volume, extracellular fluid volume, and total body water were measured in each rat by the distribution volumes of radioiodinated serum albumin, /sup 32/SO/submore » 4/, and tritiated water, respectively. The body fluid volumes, expressed per 100 g of body weight, were not different between the mestranol-treated rats and their controls at any of the three treatment times. Due to differences in body weight and lean body mass between the mestranol-treated and the control rats, these volumes also were expressed per 100 g of lean body mass. Again, no differences were observed between the mestranol-treated rats and the control rats for any of these body fluid compartments at any of the treatment times. These studies, therefore, were unable to provide evidence that increases in body fluid volumes contributed to the elevated arterial pressure in this rat model of oral contraceptive hypertension.« less
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Effects of contraceptive agents on drug metabolism in various animal species.
Briatico, G; Guiso, G; Jori, A; Ravazzani, C
1976-01-01
The effect on liver microsomal enzyme activity of three steroid contraceptive drug (SCD) combinations was compared in rats, mice and guinea-pigs. Lynestrenol plus mestranol, norethisterone plus mestranol and norethynodrel plus mestranol were given orally for 4 consecutive days (acute treatment) or 30 days (chronic treatment) at various doses eliciting an experimentally controlled antifertility activity which varied in its extent. In rats and mice all the combined treatments (with the exception of norethynodrel plus mestranol in mice) were active as inducers of liver microsomal enzymes. This induction seems to be mediated mainly by the progestogenic compounds. Oestrogens showed a very poor effect bordering on significance only in a few cases. No effect on liver microsomal protein or cytochrome P 450 concentration was obtained after treatment with doses capable of increasing the microsomal enzyme activity. The activity of the liver microsomal enzymes did not appear to be reduced immediately (2 h) after the last administration of the SCD given during 4 or 30 days. Contraceptive treatments at doses capable of eliciting complete antifertility activity were inactive on liver microsomal enzyme activity in guinea-pigs. PMID:987822
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Evaluation of R-55 and mestranol to protect Douglas-fir seed from deer mice
G.L. Crouch; M.A. Radwan
1971-01-01
Bioassays using deer mice showed that R-55 a thiocarbamate derivative applied as 2-and 5-percent coatings was ineffective in reducing consumption of Douglas-fir seed. At 2 percent3 mestranol3 an antifertility chemical3 reduced seed consumption to levels comparable with endrin applied at 0.5 percent without impairing germination.
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Dutour, Raphael; Maltais, Rene; Perreault, Martin; Roy, Jenny; Poirier, Donald
2018-03-07
RM-133 belongs to a new family of aminosteroid derivatives demonstrating interesting anticancer properties, as confirmed in vivo in four mouse cancer xenograft models. However, the metabolic stability of RM-133 needs to be improved. After investigation, the replacement of its androstane scaffold by a more stable estrane scaffold led to the development of the mestranol derivative RM-581. Using solid-phase strategy involving five steps, we quickly synthesized a series of RM-581 analogs using the recently-developed diethylsilyl acetylenic linker. To establish structure-activity relationships, we then investigated their antiproliferative potency on a panel of cancer cell lines from various cancers (breast, prostate, ovarian and pancreatic). Some of the mestranol derivatives have shown in vitro anticancer activities that are close to, or better than those observed for RM-581. Compound 23, a mestranol derivative having a ((3,5-dimethylbenzoyl)-L-prolyl)piperazine side chain at position C2, was found to be active as an antiproliferative agent (IC50 = 0.38 ± 0.34 to 3.17 ± 0.10 µM) and to be twice as active as RM-581 on LNCaP, PC-3, MCF-7, PANC-1 and OVCAR-3 cancer cells (IC50 = 0.56 ± 0.30, 0.89 ± 0.63, 1.36 ± 0.31, 2.47 ± 0.91 and 3.17 ± 0.10 µM, respectively). Easily synthesized in good yields by both solid-phase organic synthesis and classic solution-phase chemistry, this promising candidate could be used as an antiproliferative agent on a variety of cancers, notably pancreatic and ovarian cancers, both having very bad prognoses. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Clinical Evaluation of the Oral Contraceptive Use of Norethindrone 5 mg. plus Mestranol 0.075 mg
Board, John A.
1965-01-01
Norethindrone 5 mg. plus mestranol 0.075 mg., taken daily from menstrual cycle day five through day 24, was used as an oral contraceptive agent in 1248 cycles by 132 clinic patients. One hundred and one patients used this method for six months or more. There were no unplanned pregnancies. Breakthrough bleeding occurred in 38 cycles (3.0% of all cycles). In 25% of 1201 cycles the duration of menstrual flow was shorter than that which had been considered usual for the individual patient involved, and the most common weight change was a gain of 6 to 10 lb. PMID:14272499
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The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats
Heikel, T. A. J.; Lathe, G. H.
1970-01-01
1. The effect of oestrogens and progestogens and their 17α-ethinyl derivatives on bile flow, maximum rate of bilirubin secretion, serum and liver bilirubin has been studied. 2. Both 17α-ethinyl substituted oestrogens and progestogens greatly reduced the basal bile flow. The parent compounds, oestradiol-17β and 19-nortestosterone had little or no effect. 3. A much larger dose of progestogens (40 mg/kg) than oestrogens (5 mg/kg) was needed. 4. Between 12 and 48 h were required for 17α-ethinyloestradiol to produce the effect. 5. Bilirubin maximum secretion rate (Tm) was little affected, the only significant reduction being produced by the 3-methyl ether of 17α-ethinyloestradiol (mestranol). 6. Rises in serum conjugated bilirubin following infusion of bilirubin were produced by 17α-ethinyloestradiol and mestranol but not by the progestogens. PMID:5441412
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Khansary, Milad Asgarpour; Mellat, Mostafa; Saadat, Seyed Hassan; Fasihi-Ramandi, Mahdi; Kamali, Mehdi; Taheri, Ramezan Ali
2017-02-01
To analyze polymeric nanosorbents and nanofiltration/ultrafiltration membranes for hormone micropollutants removal from water effluents, here an in-through investigation on the suitability and compatibility of various polymers has been carried out. For this work, estradiol, estrone, testosterone, progesterone, estriol, mestranol, and ethinylestradiol were considered. A total number of 452 polymers were analyzed and initially screened using Hansen solubility parameters. The identified good pairs of hormones and polymers then were examined to obtain the equilibrium capacity of hormones removal from water effluents using a modified Flory-Huggins model. A distribution coefficient was defined as the ratio of hormones in water effluent phase and polymer phase. For removal of mestranol, estradiol and ethinylestradiol, no compatible polymer was identified based on initial screening of collected database. Three compatible polymers were identified for estriol. For progesterone, a wide variety of polymers was identified as good matching of polar, dispersion and hydrogen forces contributions can be observed for these pairs. For estrone, only two polymers can be proposed due to the mismatch observed between polar, dispersion and hydrogen forces contributions of other polymers and this hormone. The phase calculations showed that not all the identified good pairs could be used for practical separation applications. The domain of applicability of each good pair was investigated and potential polymers for practical micropollutants removal together with their removal capacity were represented in terms of phase envelops. The theoretical approach follows fundamental chemical thermodynamic equations and then can be simply applied for any system of interest. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Kamal, I; Hefnawi, F; Ghoneim, M; Talaat, M; Younis, N; Tagui, A; Abdalla, M
1969-10-01
To measure the effect of steroid contraceptives on lactation and baby's growth, 120 Egyptian women were given steroids in a double-blind study from 6-10 weeks postpartum until weaning. Drugs included Lyndiol 2.5 (2.5 mg lynestrenol and .075 mg mestranol, combined), Lyndiol 1 (1 mg lynestrenol and .1 mg mestranol, combined), .5 mg lynestrenol alone, continuously, Deladroxate injection (150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate, monthly), and placebo with IUD. Tests were conducted bimonthly until baby was 24 weeks, then monthly, and consisted of weighing the infant before and after suckling at 9 and 12 a.m., and weighing milk pumped from the other breast before each feeding. Average age of infant at beginning of supplementary feeding was younger than with previous children in all groups, but 23.6 weeks younger with Deladroxate and 28.2 weeks with Lyndiol 2.5. Milk yield measurements were higher from weighing the baby, but more accurate with the pump. Results, figured as percent adequacy based on infant weight, showed 50% for placebo and no drop, 45 and 46% drop after 12 weeks with Lyndiol 1 and Lyndiol 2.5, 25% drop with Deladroxate, and 20% drop with .5 mg lynestrenol. Children's growth curves were within normal range but dropped below 10th percentile for those whose mothers were given Lyndiol 2.5 or Deladroxate injection. These 2 groups of babies lost weight in the first 4 weeks and 5 died of gastroenteritis: 3 from the Deladroxate group and 2 from the Lyndiol 2.5 group. The continuous lynestrenol pill was the least harmful of the medications by all criteria.
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Uraipong, Chatchaporn; Allan, Robin D; Li, Chunhua; Kennedy, Ivan R; Wong, Victor; Lee, Nanju Alice
2017-10-01
This study reports on the potential status of 17α-ethinylestradiol (EE2) and mestranol (MeEE2) residues in aquatic environments in New South Wales (NSW), Australia, based on the analysis by a specific ELISA we developed. Polyclonal antibodies were raised against the EE2 hapten with a linker attached at the C3-position to direct the antibody binding towards the ring D of EE2/MeEE2. Using this approach, an ELISA highly specific to EE2 and MeEE2 was successfully developed, showing less than 3.1% cross-reactivity (% CR) with other major steroidal sex hormones and their derivatives. The assay performed with the limit of detection (LOD) of 0.04 ± 0.01µg/L for both EE2 and MeEE2, and the limit of quantitation (LOQ) of 0.05 ± 0.01ng/L when it was coupled with the SM2-Biobeads solid phase extraction. Prior to conducting the survey study, it was validated against the gas chromatography-mass spectrophotometry (GC-MS) method, which showed high correlation with R 2 of 0.934. Fresh surface water samples collected at different sites along Hawkesbury River in New South Wales (NSW) were analyzed for the EE2/ MeEE2 residues using the developed ELISA. The EE2/MeEE2 levels were found to range between 4.1 and 8.3ng/L in Emigrant Creek, NSW, where the primary activity was macadamia plantation, and higher levels between 15 and 29ng/L in South Creek, NSW, Greater Western Sydney at sites upstream and downstream of the municipal sewage treatment plants. Copyright © 2017 Elsevier Inc. All rights reserved.
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Morteani, Giulio; Möller, Peter; Fuganti, Andrea; Paces, Tomas
2006-06-01
The concentration of the estrogens 17beta-estradiol, estriol, estrone, 17alpha-ethinylestradiol, mestranol and norethisterone and of the anthropogenic gadolinium (Gd(ant)) has been determined in the creeks and rivers, sewage treatment plants and water works of the city of Prague. The rapid degradation of estrogens in surface water allows the estrogen concentration gradient to be used as a very precise and sensitive guideline by which to pin-point sewage leaks into surface run-off water. The rather conservative behavior of Gd(ant) in surface and ground water documents in the present case the presence of sewage water in the surface water cycle.
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Almeida, C; Nogueira, J M F
2006-06-16
In this study, stir bar sorptive extraction and liquid desorption followed by high performance liquid chromatography with diode array detection (SBSE-LD-HPLC/DAD) were combined for the simultaneous determination of nine steroid sex hormones (estrone, 17alpha-estradiol, 17beta-estradiol, 17alpha-ethynylestradiol, diethylstilbestrol, mestranol, progesterone, 19-norethisterone and norgestrel) in water and urine matrices. During the method development, it has been demonstrated that equilibrium time, ionic strength and back extraction solvents are the most important parameters to control, for determining the nine-hormones in water matrices, in which stir bars coated with 126 microl of polydimethylsiloxane were used. Assays performed on 30 ml water samples spiked at 10 microg/l levels under optimised experimental conditions, yielded recoveries ranging from 11.1+/-4.9% (17beta-estradiol) to 100.2+/-10.4% (mestranol), showed that the methodology is well described by the octanol-water partition coefficients (K(PDMS/W) approximately K(O/W)) for the latter, while pronounced deviations to the theoretical efficiency (K(PDMS/W) not equal K(O/W)) were observed for the remaining hormones. From calibration studies, a good analytical performance for all hormones was attained, including a suitable precision (2.1-17.1%), low limits of detection (0.3-1.0 microg/l) and an excellent linear dynamic range (1.25-50.0 microg/l). Assays on environmental water and urine matrices showed recovery yields in worthy good agreement with the spiking level (10 microg/l), and suitability for profiling low microg/l levels of natural hormones in urine samples taken from pregnant women. The present methodology is easy, reliable and sensitive at the trace level, only requiring a low sample volume, showing to be a good analytical alternative to routine quality control for environmental and biomedical laboratories.
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Effect of chronic administration of mestranol, tamoxifen, and toremifene on hepatic ploidy in rats.
Dragan, Y P; Shimel, R J; Bahnub, N; Sattler, G; Vaughan, J R; Jordan, V C; Pitot, H C
1998-06-01
The nonsteroidal antiestrogen tamoxifen increases the incidence of rat liver cancer through a variety of mechanisms. To compare the effects of tamoxifen (TAM) and a structurally similar analog toremifene (TOR) on rat liver, we determined the ploidy distribution for hepatocytes isolated from rats treated for 18 months with these antiestrogens or the estrogenic compound mestranol (MS). Female Sprague-Dawley rats were subjected to a 70% partial hepatectomy and administered the solvent, trioctanoin, or diethylnitrosamine (10 mg DEN/kg). After a 2-week recovery from the surgery, the rats were administered a basal diet or one containing TAM (250 or 500 ppm), TOR (250, 500, or 750 ppm), or MS (0.2 ppm) for 18 months. Pathologic changes in the liver were examined in the 15-22 rats per treatment group at the 18-month time point. An increased incidence of hepatocellular carcinomas (HCC) was detected in the 500 ppm TAM group, but not with the other treatments that did not include DEN. Both TOR and TAM promoted formation of DEN-initiated HCCs. At sacrifice, four to five rats per group were perfused and the hepatocytes isolated and cultured. Karyotypic analysis was performed on colcemid-blocked cells after 2 days in culture. The hepatic ploidy distribution was characterized in Giemsa-stained metaphase spreads. These studies indicated that chronic treatment with TAM alone resulted in a shift from tetraploid to diploid, as was also observed for rats treated once with DEN. TOR and MS alone did not cause this change in hepatic ploidy at the doses examined. A shift toward an increased content of diploid hepatocytes occurred in all rats treated once with DEN followed by TAM, TOR, or MS. These results indicate that tamoxifen administration results in a shift toward growth of diploid hepatocytes, thus contributing to its carcinogenic action in the rat liver.
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Sturtevant, R P
1970-08-01
64 women clients of Planned Parenthood of Evansville (Indiana) used Enovid (5 mg norethynodrel and .075 mg mestranol, combined) for 2 1/2 to 6 years. A "25-Month Club" card and free pills were given to encourage continuation in the study, and 33 women (52%) remained until study termination. The group ranged in age from 18-40 years, mean 27 years, and in parity 0 to 12, mean 4. No pregnancies, cancer of reproductive organs or thromboembolism occurred. Side effects, recorded by interview according to a standard form, included: cervicitis 48%, vaginal discharge 42%; dysmenorrhea 61% pretreatment, 42% improved, 11% new symptoms; breast complaints 33%; 2-15 lb weight gain 19%. 12% reported no side effects, although the author commented that the 25-Month Club policy might have discouraged reporting of side effects.
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Oral contraceptives and the prothrombin time.
Pangrazzi, J; Roncaglioni, M C; Donati, M B
1980-02-02
Dr. De Teresa and others reported that mean prothrombin time ratio of 12 patients on long-term anticoagulation with warfarin was significantly higher when they were also taking oral contraceptives (OCs). A study of prothrombin complex activity was recently conducted in female rats treated with an estrogen-progestogen combination (lynestrenol 5 mg; mestranol 0.3 mg/kg body weight) which resulted in a 100% infertility in this species. After 1 treatment for only 1 estral cycle, OC-treated rats had a significantly longer Normotest clotting time (37.7+ or-0.5 sec) than control rats (31.0+or-0.4); the difference was even more notable after 10 cycles. Although this finding has not been reported in women on OCs, it may be that the estrogen-induced "lability" of the prothrombin complex occurs in humans only in special conditions, such as anticoagulation. Alternatively, liver dysfunction occurring among women on OCs may be responsible for reduced metabolism of warfarin, contributing to the effectiveness of the anticoagulation. Further pharmacology studies should be done to clarify the interaction between OCs and oral anticoagulants.
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Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey.
Weininger, J; King, J C
1982-06-01
Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.
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Ozone oxidation of oestrogenic active substances in wastewater and drinking water.
Baig, S; Hansmann, G; Paolini, B
2008-01-01
Ozone oxidation is proven to be an effective solution for the degradation of selected oestrogenic active substances detected in secondary wastewaters such as beta-oestradiol, oestrone, oestriol, 17-alpha-ethinyloestradiol, mestranol, daidzeine, beta-sitosterol, bisphenol A, norethisterone, 4-tert-octylphenol and 4-iso-nonylphenol, up to their limit of detection. The matrix-effect of wastewater was investigated performing ozone experiments under batch mode and continuous mode using drinking water and a wastewater issued from a local plant both spiked with the non-detected substances. The results obtained indicate that the wastewater matrix greatly affects the kinetics of ozone reaction with these substances but does not really change the related reactivity scale. The ozone dose corresponding to the full conversion of target EDCs consequently increases as their oxidation takes place competing with reactions of background pollutants represented by the COD and DOC content. However, a usual dose close to 12 mg/L was found sufficient to provide high degradation yields for all substances studied while 35% of COD was removed. This is a contribution to the numerous current works focused on technologies able to improve the quality of water discharged from wastewater treatment plants, both considering conventional parameters and emerging contaminants. IWA Publishing 2008.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Anastas, M.Y.; Caplan, P.E.; Froehlich, P.A.
An on-site visit was made to the Ortho Pharmaceutical Corporation (OPC), Raritan, New Jersey to evaluate methods of controlling exposure to hazardous materials during the manufacturing of medications. OPC produced oral-contraceptive tablets containing norethindrone (NOR), mestranol, and ethynylestradiol (EE). Ventilation was an important engineering control at this site. Other engineering controls included the isolation of work procedures and automation of work practices for weighing ingredients, granulation of substances, tableting, and packaging. Area samples were taken for air monitoring of steroid concentration levels in each manufacturing area. Access to the work areas was only through the locker rooms. Samples taken inmore » the locker rooms revealed no detectable contaminant levels. Workers performing high risk activities wore air supplied vinyl suits and disposable rubber gloves. The vinyl suits had overshoes attached. For moderate risk activities the workers wore a disposable suit, rubber gloves and shoe covers. Appropriate respirators were provided. Workers in low risk activities wore disposable rubber gloves and appropriate respirators. Sampling indicated that processing workers experienced breathing-zone levels outside their vinyl suits of 16.40 and 0.36 micrograms/cubic meter of NOR and EE, respectively.« less
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Matić, Ivana; Grujić, Svetlana; Jauković, Zorica; Laušević, Mila
2014-10-17
In this paper, development and optimization of new LC-MS method for determination of twenty selected hormones, human/animal and plant sterols in river sediments were described. Sediment samples were prepared using ultrasonic extraction and clean up with silica gel/anhydrous sodium sulphate cartridge. Extracts were analyzed by liquid chromatography-linear ion trap-tandem mass spectrometry, with atmospheric pressure chemical ionization. The optimized extraction parameters were extraction solvent (methanol), weight of the sediment (2 g) and time of ultrasonic extraction (3× 10 min). Successful chromatographic separation of hormones (estriol and estrone, 17α- and 17β-estradiol) and four human/animal sterols (epicoprostanol, coprostanol, α-cholestanol and β-cholestanol) that have identical fragmentation reactions was achieved. The developed and optimized method provided high recoveries (73-118%), low limits of detection (0.8-18 ng g(-1)) and quantification (2.5-60 ng g(-1)) with the RSDs generally lower than 20%. Applicability of the developed method was confirmed by analysis of six river sediment samples. A widespread occurrence of human/animal and plant sterols was found. The only detected hormone was mestranol in just one sediment sample. Copyright © 2014 Elsevier B.V. All rights reserved.
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[Effect of oral contraceptives on the psyche and on sexuality].
Nahrendorf, G; Carol, W; Klinger, G
1978-01-01
The problem of whether or not oral contraceptives affect the psychic function of the female is still controversal. The purpose of the present investigation was to study the occurrence of psychic and sexual effects in women taking either Ovosiston (mestranol 0,08 mg + chlormadinone acetate 2, 0 mg) or Non-Ovlon (ethinylestradiol 0,05 mg + norethisterone acetate 1,0 mg). 186 somatically healthy women were subject to two interviews, immediately before the start of therapy and six months after it. Most of the patients recorded distinctly alterations of their mood, their initiative, their elemental desires such as appetite, sleep, need of warmth, and their sexual behaviour. 73 of them noted a change in their emotional pattern, which was positive in 34 and negative in 39 cases. 99 women reported changes in their elemental desires. 136 patients exhibited alterations of their sexual behaviour, which were assessed as an improvement or impairment in 108 and 28 cases, respectively. There is a statistically significant correlation between the impairment of sexual function and the incidence of other untoward side effects. On the other hand, negative suggestion by poor experience of other women on by the influence of mass media seems to play a minor role in producing changes of sexual behaviour. There is, however, a clearcut relationship between negative suggestion and the incidence of unfavourable emotional alterations. The findings are discussed with reference to their clinical significance.
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Nelson, Anita
2010-08-09
To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women's desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors.
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Xenobiotic interaction with and alteration of channel catfish estrogen receptor.
Nimrod, A C; Benson, W H
1997-12-01
In teleostean in vivo studies, the vitellogenin response to environmental estrogens is not completely predicted by mammalian literature. One possible explanation for differences is heterogeneity of the estrogen receptor (ER) structure between species. Therefore, ER from channel catfish (Ictalurus punctatus) hepatic tissue was characterized by binding affinity for several compounds. Affinity was indirectly measured as potency of the chemical for inhibiting binding of radiolabeled estradiol (E2) to specific binding sites. The order of potency among therapeutic chemicals was ethinylestradiol > unlabeled E2 = diethylstilbestrol > mestranol > tamoxifen > testosterone. Unlabeled E2 had an IC50 of 2.2 nM. Several environmentally relevant chemicals were evaluated in a similar manner and the order of potency established was the o-demethylated metabolite of methoxychlor (MXC) > nonylphenol (NP) > chlordecone > MXC > o,p'-DDT > o,p'-DDE > beta-hexachlorocyclohexane. Demethylated MXC had an IC50 1000-fold greater than that of E2. Of the most potent inhibitors, NP appeared to be a competitive inhibitor for the same binding site as E2, while o-demethylated MXC had a more complex interaction with the receptor protein. ER from nonvitellogenic females was determined to have a Kd value of 1.0 to 1.3 nM. Because E2 has been reported to up-regulate teleostean ER, the hepatic ER population following in vivo xenobiotic exposure was assessed. NP significantly increased ER per milligram hepatic protein almost to the same extent as E2, but did not increase Kd to the same extent as E2.
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Occurrence and fate of hormone steroids in the environment.
Yin, Guang-Guo; Kookana, Rai S; Ru, Ying-Jun
2002-12-01
Hormone steroids are a group of endocrine disruptors, which are excreted by humans and animals. In this paper, we briefly review the current knowledge on the fate of these steroids in the environment. Natural estrogenic steroids estrone (E1), 17beta-estradiol (E2) and estriol (E3) all have a solubility of approximately 13 mg/l, whereas synthetic steroids 17alpha-ethynylestradiol (EE2) and mestranol (MeEE2) have a solubility of 4.8 and 0.3 mg/l, respectively. These steroids have a moderate binding on sediments and are reported to degrade rapidly in soil and water. Estrogenic steroids have been detected in effluents of sewage treatment plants (STPs) in different countries at concentrations ranging up to 70 ng/l for E1, 64 ng/l for E2, 18 ng/l for E3 and 42 ng/l for EE2. E2 concentrations in river waters from Japan, Germany, Italy and the Netherlands ranged up to 27 ng/l. In addition, E2 concentrations ranging from 6 to 66 ng/l have also been measured in mantled karst aquifers in northwest Arkansas. This contamination of ground water has been associated with poultry litter and cattle manure waste applied on the land. Although hormone steroids have been detected at a number of sources worldwide, currently, there is limited data on the environmental behaviour and fate of these hormone steroids in different environmental media. Consequently, the exposure and risk associated with these chemicals are not adequately understood.
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Nelson, Anita
2010-01-01
Aim: To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. Methods: This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. Results: The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. Conclusion: The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women’s desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors. PMID:21072303
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NASA Astrophysics Data System (ADS)
Lee, Youngme; Sah, Eric; Sah, Hongkee
2015-11-01
The objective of this study was to develop a new oil-in-water emulsion-based nanoencapsulation method for the preparation of PLGA nanoparticles using a non-halogenated solvent. PLGA (60-150 mg) was dissolved in 3 ml of methyl propionate, which was vortexed with 4 ml of a 0.5-4 % polyvinyl alcohol solution. This premix was sonicated for 2 min, added into 30 ml of the aqueous polyvinyl alcohol solution, and reacted with 3 ml of 10 N NaOH. Solvent removal was achieved by the alkaline hydrolysis of methyl propionate dissolved in an aqueous phase into water-soluble methanol and sodium propionate. It was a simple but effective technique to quickly harden nanoemulsion droplets into nanoparticles. The appearing PLGA nanoparticles were recovered by ultracentrifugation and/or dialysis, lyophilized with trehalose, and redispersed by water. This nanoencapsulation technique permitted a control of their mean diameters over 151.7 ± 3.8 to 440.2 ± 22.2 nm at mild processing conditions. When the aqueous polyvinyl alcohol concentration was set at ≥1 %, nanoparticles showed uniform distributions with polydispersity indices below 0.1. There were no significant changes in their mean diameters and size distribution patterns before and after lyophilization. When mestranol was encapsulated into nanoparticles, the drug was completely nanoencapsulated: depending on experimental conditions, their encapsulation efficiencies were determined to be 99.4 ± 7.2 to 105.8 ± 6.3 %. This simple, facile nanoencapsulation technique might have versatile applications for the preparation of polymeric nanoparticulate dosage forms.
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Ternes, T A; Kreckel, P; Mueller, J
1999-01-12
Aerobic batch experiments containing a diluted slurry of activated sludge from a real sewage treatment plant (STP) near Frankfurt/Main were undertaken, in order to investigate the persistence of natural estrogens and contraceptives under aerobic conditions. The batch experiments showed that while in contact with activated sludge the natural estrogen 17 beta-estradiol was oxidized to estrone, which was further eliminated in the batch experiments in an approximate linear time dependence. Further degradation products of estrone were not observed. 16 alpha-hydroxyestrone was rapidly eliminated, again without detection of further degradation products. The contraceptive 17 alpha-ethinylestradiol was principally persistent under the selected aerobic conditions, whereas mestranol was rapidly eliminated and small portions of 17 alpha-ethinylestradiol were formed by demethylation. Additionally, two glucuronides of 17 beta-estradiol (17 beta-estradiol-17-glucuronide and 17 beta-estradiol-3-glucuronide) were cleaved in contact with the diluted activated sludge solution and thus 17 beta-estradiol was released. The glucuronidase activity of the activated sludge was further confirmed by the cleavage of 4-methylumbelliferyl-beta-D-glucuronide (MUF-beta-glucuronide) in a solution of a activated sludge slurry and Milli-Q-water (1:100, v/v). The turnover rate obtained was approximately steady state, with a turnover rate of 0.1 mumol/l for the released MUF. Hence, it is very likely that the glucuronic acid moiety of 17 beta-estradiol glucuronides and other estrogen glucuronides become cleaved in a real municipal STP, so that the concentrations of the free estrogens increase.
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Liao, Keren; Mei, Meng; Li, Haonan; Huang, Xiaojia; Wu, Cuiqin
2016-02-01
The development of a simple and sensitive analytical approach that combines multiple monolithic fiber solid-phase microextraction with liquid desorption followed by high-performance liquid chromatography with diode array detection is proposed for the determination of trace levels of seven steroid sex hormones (estriol, 17β-estradiol, testosterone, ethinylestradiol, estrone, progesterone and mestranol) in water and urine matrices. To extract the target analytes effectively, multiple monolithic fiber solid-phase microextraction based on a polymeric ionic liquid was used to concentrate hormones. Several key extraction parameters including desorption solvent, extraction and desorption time, pH value and ionic strength in sample matrix were investigated in detail. Under the optimal experimental conditions, the limits of detection were found to be in the range of 0.027-0.12 μg/L. The linear range was 0.10-200 μg/L for 17β-estradiol, 0.25-200 μg/L estriol, ethinylestradiol and estrone, and 0.50-200 μg/L for the other hormones. Satisfactory linearities were achieved for analytes with the correlation coefficients above 0.99. Acceptable method reproducibility was achieved by evaluating the repeatability and intermediate precision with relative standard deviations of both less than 8%. The enrichment factors ranged from 54- to 74-fold. Finally, the proposed method was successfully applied to the analysis of steroid sex hormones in environmental water samples and human urines with spiking recoveries ranged from 75.6 to 116%. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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[Hyperplastic changes and oral contraceptives in Anglo-Saxon countries].
Markuszewski, C
1978-09-18
One of the major problems being researched and studied by the World Health Organization is the incidence of harmful side effects in users of steroid contraceptives. A literature search indicates that Anglo-Saxon countries report alarming hyperplastic changes, particularly in the liver, blood clots, hyperlipidemia leading to high blood pressure, porphyria, atypical leiomyomas and cervical hyperplasia. Currently attention is being focused on the relationship between steroid contraceptives and breast cancer. Fazala and Paffenbarger in their study of 1770 women found such benign changes as fibroadenoma, mastopathia fibrosa cystica and papilloma intraductale. In women who had used oral contraceptives for 2-4 yrs, malignancies were 1.9% to 2.5% more frequent than in non-users; in 6 yrs of use, 11 times greater than in non-users. Estrogens, particularly mestranol has been recognized as being harmful to the liver. Length of usage is a definite factor. Beginning with 1960, relatively frequent occurrences of hepotoma in young women on the pill were noted. Caught at an early stage, peliosis hepatis can be reversed if the patient discontinues the use of contraceptives. In some cases, even after a long interval of 6 months to 10 yrs, the disease continued to develop. Liver cell adenoma in the U. S. occurs 1/500,00 to 1/1,000,000. After 5 to 7 yrs of using oral contraceptives, the chance of developing liver cell adenoma is 5 times greater; after 10 yrs of use, 35 times greater. Hepatomas rupture in 43.4% of cases when the patient had been on a contraceptive, while in only 22.2% in cases of non-users. The literature which the author investigated did not establish a clear proof that the hyperplastic changes discussed were due exclusively to usage of oral contraceptives.
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Diak, James; Örmeci, Banu
2017-04-01
This study examined the individual and combined effects of potassium ferrate(VI) additions and freeze-thaw conditioning for the treatment and dewatering of wastewater sludge in cold climates, with particular focus on the inactivation of fecal coliforms and oxidation of estrogens, androgens, and progestogens. The first phase of the study evaluated the effects of potassium ferrate(VI) pre-treatment followed by freeze-thaw at -20 °C using a low (0.5 g/L) and high (5.0 g/L) dose of potassium ferrate(VI). The results showed that pre-treatment of anaerobically digested sludge with 5 g/L of potassium ferrate(VI) reduced the concentration of fecal coliforms in the sludge cake to below 100 MPN/g DS. The second phase evaluated the ability of ferrate(VI) to oxidise selected hormones in sludge. Anaerobically digested sludge samples were spiked with 10 different hormones: estrone (E1), 17α-estradiol, 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), equilin, mestranol, testosterone, norethindrone and norgestrel in two groups of low (3-75 ng/mL) and high (12-300 ng/L) concentration ranges of hormones. The samples were treated with either 0.5 or 1.0 g/L of potassium ferrate(VI), and hormone concentrations were measured again after treatment. Potassium ferrate(VI) additions as low as 1.0 g/L reduced the concentration of estrogens in sludge. Potassium ferrate(VI) additions of 0.5 and 1.0 g/L were less effective at reducing the concentrations of androgens and progestogens. Increasing ferrate(VI) dose would likely result in more substantial decreases in the concentrations of fecal coliforms and hormones. The results of this study indicate that the combined use of freeze-thaw and ferrate(VI) has the potential to provide a complete sludge treatment solution in cold regions.
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Oral contraceptives and cancer of the liver: a review with two additional cases.
Helling, T S; Wood, W G
1982-07-01
The hormonal milieu that follows the ingestion of contraceptive agents promotes the growth of hepatic tumors, particularly hepatocellular adenomas. Evidence that the use of contraceptive drugs can also cause carcinoma of the liver is less convincing; this article describes the cases of 2 young women who had taken contraceptives and contracted hepatocellular carcinoma. Both women had no prior history of liver disease and died as a result of the carcinoma. Hepatocellular carcinoma has been a distinctly uncommon disease in the U.S. ranging in incidence from 0.23-0.47% in reported autopsy cases and being typically described as occurring mostly in men over 50 and associated with preexisting cirrhosis. Recent surveys show a greater proportion of female patients; in the U.S. patients at risk now include women in the reproductive age group with no history of prior liver disease. Some recorded changes in the human liver caused by oral contraceptives (OCs) include: 1) impairment of bile secretory function, 2) hepatomegaly associated with peripheral and midzonal sinusoidal congestion, and 3) peliosis hepatis. Significant risk factors in the occurrence of hepatic tumors in OC users are: 1) prolonged usage (1-3 years), 2) age over 30, and 3) use of compounds of high hormonal potency. Products containing mestranol have been implicated to a greater degree than those containing ethinyl estradiol. The link between use of OCs and development of hepatocellular carcinoma is not certain; however, the latter has been firmly linked with the use of anabolic steroids in men. Specifically only the C-17 substituted anabolic steroids oxymetholone and methyltestosterone have been implicated which are closely related to the C-17 substituted 19-norsteroids used in OCs. The following observations have also been made: 1) when hepatocellular carcinoma occurs in women it is mostly in those of reproductive age, and 2) OCs are associated with the development of benign hepatic tumors. Withdrawal from OCs is almost uniformly recommended after definitive diagnosis of a hepatic tumor along with surgery to avoid the risk of rupture and possible mortality.
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NASA Astrophysics Data System (ADS)
Malisza, Krisztina Laura
Sterically crowded organometallic complexes present fascinating problems of structure and molecular dynamics. Tetrahedral clusters such as (RCequivCR ^')rm(C_5H_5)_2M _2(CO)_4, where M = Mo or W, crystallize in conformations possessing three terminal carbonyls while the fourth is semi-bridging. However, these ligands undergo a rapid exchange process which can be followed by variable -temperature NMR spectroscopy. When the R substituent is derived from a chiral natural product, the low temperature NMR spectra reveal the presence of diastereomers which are interconvertible via rotations of the organometallic vertices. The fluxional behaviour of tetrahedral clusters containing such vertices as Co(CO)_3, Fe(CO)_3 or rm(C_5H _5)Mo(CO)_2 can be rationalized by means of molecular orbital calculations at the extended Huckel level of approximation. These studies show that the barriers to vertex rotation can usually be traced to one principal orbital interaction in each case. However, in rm(C_5H_5)_2Mo_2(CO) _4(R-CequivC-R) clusters, the barriers are primarily steric in character. The ability of transition metal clusters to delocalize electronic charge is well known and, in principle, could be used to stabilize intermediates of biochemical significance. Treatment of 2-methylcyclopentanone with an alkyne anion was carried out in order to generate 1-alkynyl-2-methylcyclopentanols in which the methyl and alkynyl groups are trans diaxial; the aim was to mimic the "D"-ring of the steroidal contraceptive mestranol. In fact, the major epimer was the one in which the methyl and alkynyl substituents were disposed in a cis manner. The conformation of 2-methyl-1-phenylethynylcyclopentanol 47 was elucidated by two-dimensional NMR techniques. Moreover, the structure of 47 and also of its rm Co _2(CO)_6 derivative have been determined crystallographically. Protonation of the dicobalt or dimolybdenum complexes of 47 lead to stable cations; treatment of these cations with nucleophiles results in elimination of water to yield 2-methylcyclopentene derivatives of which the dimolybdenum cluster has been characterized by x-ray crystallography. The sterically crowded complexes rm(C _6H_5)_3SiOH[ Cr(CO)_3 ]_{n}, where n = 1,2,3, have also been characterized X-ray crystallographically and all three have propellor-type geometries. The question of whether the phenyl ring rotations are correlated has been studied by variable-temperature NMR spectroscopy. These systems do not yield stable silicenium cations, but the analogous Cr(CO)_3 complex of triphenylcarbinol not only shows fluxional behaviour but also yields a metal -stabilized cation. The pathway for phenyl rotations in such systems can be followed via a Dunitz-type trajectory approach in which a number of x-ray structures were analyzed.