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At least 91 records · Page 5Linked to original sources
PubMed1986

The lack of effect of sodium valproate on the pharmacokinetics of oral contraceptive steroids.

Patients taking anticonvulsants such as phenobarbitone, phenytoin and carbamazepine together with their oral contraceptive steroid may suffer contraceptive failure because of the enzyme-inducing properties of these anticonvulsants. We have examined, in six women, the effect of sodium valproate, an effective broad spectrum anticonvulsant, on the area under the plasma concentration versus time profile (AUC) of ethinyloestradiol (EE2) and levonorgestrel (Ng). Prior to sodium valproate therapy the mean AUC for EE2 was 880 +/- 109 pg/ml X h (+/- S.E.) and for levonorgestrel it was 29.1 +/- 2.9 ng/ml X h (n = 4). Between two and four months after sodium valproate therapy the mean AUC figures had not changed significantly, the figure for EE2 being 977 +/- 130 pg/ml X h and for levonorgestrel 29.2 +/- 1.9 ng/ml X h (p greater than or equal to 0.1 in each case). We conclude that sodium valproate in the dose used (200 mg b.d.) does not interact with oral contraceptive steroids.

Adolescent↗
PubMed1986

The relative bioavailability of levonorgestrel and ethinyl estradiol administered as a low-dose combination oral contraceptive.

The relative bioavailability of levonorgestrel (LNG) and ethinyl estradiol (EE) administered concomitantly both as an oral tablet and as a solution was assessed in a randomized two-period crossover study in 24 healthy women. Serum concentrations were monitored for 96 h after each administration. The relative bioavailability (Fr) of LNG in the tablet with respect to the solution was 107%; thus the two formulations were bioequivalent with respect to LNG. The relative bioavailability of EE, however, was significantly lower for the tablet (Fr 83%) compared to the solution. This difference may have been due to either decreased absorption or enhanced presystemic elimination of EE from the tablet formulation.

Adult↗
PubMed1987

Mechanism of action of intrauterine devices: biochemical changes.

The mechanism of action of intrauterine devices varies from one type of device to another, although the principle of action is the same, namely, to interfere with the physiology of reproduction at the endometrial level. The biochemical changes of the endometrial tissue and the composition of the uterine fluid have been reviewed in relation to the use of inert, copper-medicated and steroid-releasing IUDs. All IUDs, whether inert or medicated, provoke a significant increase in the number of neutrophils, mononuclear cells and plasma cells, the presence of which is unrelated to the tissue infiltration of inflammatory cells occurring pre-menstrually of the normal menstrual cycle. The increase of leucocytes in IUD-users is compatible with a foreign body reaction which may be related to the antifertility effect. The addition of copper to an inert IUD has been shown to significantly alter the metabolism of the endometrial cells, e.g. the enzymatic activity and the DOVA-synthesis. The steroid-medicated IUDs represent a new approach to intrauterine contraception where the morphology of the endometrium is considerably altered, showing massive decidual changes, atrophic glands and sometimes atrophy of the whole functional layer. In addition, there is an important foreign body reaction, similar to that of the inert IUDs. The enzymatic activity, as well as the proliferative activity was significantly altered in the endometrium of these IUD-users. Changes in the endometrial fibrinolytic activity in IUD-users have been demonstrated to be related to the presence of irregular bleeding. Micro-traumata of the endometrium and the increased fibrinolytic activity may also interfere with the protective processes present in the physiologically normal endometrium. Further studies on the factors influencing the fertilizing ability of the spermatozoa in the female genital tract, as well as on the conditions of the human endometrium required for the implantation of a blastocyst, may yield important information for the improvement of intrauterine contraception.

Endometrium↗
PubMed1988

The effects of Norplant on clinical chemistry in Singaporean acceptors after 1 year of use: metabolic changes.

In this longitudinal study involving 100 Singaporean acceptors, the effects of NORPLANT on their metabolic function was evaluated. With respect to liver function, the results indicate possible hepatocellular dysfunction; there was a significant rise in mean serum bilirubin from 0.55 mg/dl to 0.87 mg/dl after 12 months of use (p less than 0.001). This rise could not be attributed to a skewed distribution of mean value as the difference achieved statistical significance using the paired 't' test as well as the Wilcoxon signed rank test using the median distribution. In terms of the effects of NORPLANT on lipid metabolism, we have demonstrated a significant rise in HDL-cholesterol (1.08 mmol/l +/- 0.34 to 1.13 mmol/l +/- 0.24; p less than 0.05) with significant decreases in mean serum triglycerides (1.21 mmol/l +/- 0.74 to 0.89 mmol/l +/- 0.45; p less than 0.002) and total cholesterol (5.05 mmol/l +/- 1.02 to 4.64 mmol/l +/- 0.81; p less than 0.001) after one year of use. There was also a significant rise in the HDL-cholesterol/total cholesterol ratio after 1 year (0.225 +/- 0.086 cf 0.250 +/- 0.059; p less than 0.001). As we have not incorporated a simultaneous non-pill treated control group, the observed changes in lipoprotein lipids could be attributed to extraneous factors such as diet, exercise or other environmental changes. Nevertheless, the findings though speculative indicate NORPLANT use to be non-contributory to cardiovascular risk and indeed it may be protective factor against such risks in this population. The use of NORPLANT was not associated with any significant effect on glucose tolerance after 12 months of use.

Adult↗
PubMed1991

Effects of various IUDs on the composition of cervical mucus.

The influence of three different intrauterine devices on the composition of cervical mucus was studied. The amount of mucin, albumin and immunoglobulin G was estimated. After the insertion of an inert IUD, a decrease in mucin was observed. During copper-IUD use the content of mucin, albumin and IgG was increased in cervical mucus, while weight was not affected. In the levonorgestrel-IUD users, ovulation was inhibited in 2 out of 8 women. Mucus weight was increased. The amounts of mucin, albumin and IgG were not changed. In an in vitro experiment the effect of copper-IUDs on autooxidation of cholesterol was studied. There was an extensive conversion of cholesterol but addition of albumin quenched the oxidation of cholesterol. It is suggested that the increased secretion of albumin induced by copper-IUD users may offer protection against copper-induced cell damage.

Body Weight↗
PubMed1992

Effect of Norplant implants on liver, lipid and carbohydrate metabolism.

In this study involving 100 women, the metabolic changes seen with Norplant use were evaluated. Besides a significant increase in serum bilirubin, there were no other changes in liver function to suggest possible hepatocellular dysfunction at the end of five years. Even the raised mean levels of bilirubin remained within the normal clinical range for the local population. As regards lipid metabolism, total triglycerides, cholesterol and LDL-cholesterol were decreased through the five years of Norplant use. The HDL-cholesterol showed a significant increase in the first year; it then decreased over the years to its preinsertion level at the end of five years. As a result, the HDL-cholesterol/Total cholesterol - HDL-cholesterol showed a significant increase in the first year and then decreased to almost its preinsertion value at the end of five years. The findings appear to indicate Norplant use not to be contributory to cardiovascular risk. The use of Norplant was not associated with any significant effect on carbohydrate metabolism.

Bilirubin↗
PubMed1991

Oral contraceptives stimulate the excretion of clofibric acid glucuronide in women and female rats.

1. Glucuronidation of clofibric acid, the pharmacologically active form of the hypolipidemic drug clofibrate was investigated in a human population, either in vitro with liver homogenates from biopsies, or after ingestion of the drug and determination of the urinary metabolite. No difference in the glucuronidation rate according to age of the patients was observed. Bilirubin but not clofibric acid glucuronidation was significantly higher in women (106% increase), when expressed per gram of tissue. 2. The excretion of clofibryl glucuronide in women who took oral contraceptives was significantly enhanced by 25%. 3. In female rats, treatment with the contraceptive agent norethindrone also stimulated by 48% the formation of clofibrylglucuronide in liver microsomes.

Adult↗
PubMedDate not supplied

Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene.

A series of 17 alpha-acetylenic steroids was examined with regard to ability to inactivate human liver microsomal cytochrome P-450 (P-450) IIA4, an enzyme involved in the oxidation of a number of drugs, carcinogens, and steroids, including estrogens and progestogens. Of the eight compounds tested, gestodene was found to be particularly active as a mechanism-based inactivator of P-450 IIIA4. Inhibition of both microsomal nifedipine oxidation and 17 alpha-ethynylestradiol (EE) 2-hydroxylation was dependent upon NADPH and gestodene concentration. Rates of inactivation were pseudo first order-values of kinactivation = 0.4 min-1 and Ki = 46 microM and a partition ratio of 9 were calculated. The kinactivation is approximately 50-fold greater than estimated for EE and is one of the highest reported for P-450 mechanism-based inactivators. Spectrally detectable P-450 was also destroyed in microsomes, but several experiments indicate that little covalent binding to amino acid residues of P-450 IIIA4 occurs. Microsomal inactivation of P-450 could be blocked by the presence of other P-450 IIIA4 substrates, and several activities catalyzed by other P-450s were not inhibited under conditions in which greater than 90% of P-450 IIIA4 was inactivated. Consideration of structure/activity relationships among the 17 alpha-acetylenic steroids examined indicates that the delta 15 double bond is critical but is not in itself sufficient for the inactivation process, which is postulated to result from attack of P-450 on the substituted acetylenic carbon and lead to porphyrin N-alkylation. The effectiveness of this mechanism-based inactivator may account for reports of increased estrogen and steroid levels in some women using gestodene in oral contraceptives.

Contraceptives, Oral↗
PubMed1992

Concentration of fat, protein, lactose and energy in milk of mothers using hormonal contraceptives.

Energy, protein, lactose and fat were studied in the milk of mothers who were using different types of contraceptives. One hundred and eleven mothers made up the following groups. C: control (barrier and natural methods, or sterilization), n = 22; combined pill: LDP (low dose pill (levonorgestrel 0.15 mg + ethinylestradiol 0.03 mg)), n = 12 and MDP (medium dose pill (levonorgestrel 0.25 mg + ethinylestradiol 0.05 mg)), n = 13; MP (minipill (norethindrone 0.35 mg)), n = 37; DMPA (injectable progesterone (depot medroxiprogesterone acetate 150 mg)), n = 17; and IUD (plastic or copper intrauterine device), n = 10. The mean stages of lactation were, respectively, 15, 17, 5, 9, 5 and 9 weeks. The mean duration of observation for the study groups ranged from 2 to 4 weeks. Milk samples were collected before and after initiation of treatment (mean = 20 days; range = 14-103 days). The stage of lactation and the interval of nursing before sampling were recorded so that statistical account could be taken of these uncontrollable sources of variability. When incorporated as covariates, they showed that no significant differences existed between the groups tested, either before or after treatment.

Adult↗
PubMed1987

Pharmacokinetics of contraceptive steroids in patients with cystic fibrosis.

The pharmacokinetics of the commonly used contraceptive steroids ethinyloestradiol and levonorgestrel were investigated after oral and intravenous administration in six women with cystic fibrosis. The results were compared with data obtained from healthy women of similar age. The total body clearance of ethinyloestradiol was significantly higher in the patients with cystic fibrosis (0.61 (SD 0.19) l/h/kg) than in control women (0.32 (0.16) l/h/kg; p less than 0.02). In addition, the oral bioavailability of ethinyloestradiol was greater in women with cystic fibrosis than in controls (76.9% (11.7%) compared with 47.3% (7.5%); p less than 0.001). As a result of these two changes, the area under the plasma concentration--time curve after an oral dose of ethinyloestradiol was similar in patients and controls. The pharmacokinetics of levonorgestrel did not differ significantly between patients with cystic fibrosis and healthy women. The data suggest that women with cystic fibrosis will receive similar contraceptive protection from these steroids as do healthy women.

Adult↗
PubMed1991

Pharmacokinetics of levonorgestrel in 18 women after 1 month of treatment with a triphasic oral contraceptive.

A triphasic levonorgestrel (LNG)- and ethinylestradiol-containing oral contraceptive was administered to 18 women. Plasma samples were obtained throughout a treatment cycle just before drug administration and on the last treatment day (day 21), several plasma samples were collected from each individual up to 48 h postadministration. LNG was determined by radioimmunoassay in all plasma samples. In addition, the concentration of sex-hormone-binding globulin (SHBG) was determined in plasma samples collected from the same subjects during treatment, as well as during a pre- and a posttreatment cycle. During the treatment cycle, plasma levels of LNG determined just before drug administration increased and reached steady state at about day 16. This increase was due to an increased dose of LNG according to the triphasic dose regimen, a concomitantly ethinylestradiol-induced increase in SHBG and due to pharmacokinetic accumulation, since LNG had a terminal half-life of approximately 28.5 h and the dosing interval was 24 h. Steady-state levels and pharmacokinetic parameters of LNG determined on the last day of treatment were in good accordance with previously published results.

Adolescent↗
PubMed1991

Changes in the plasma levels of proteins C and S in young women on low-dose oestrogen oral contraceptives.

The physiological importance of proteins C and S as natural anticoagulants is demonstrated by the increased risk of thromboembolic disease among subjects with hereditary deficiency of both proteins. In the present study the effects were evaluated of low-dose oestrogen oral contraceptives (OC) on the plasma levels of immunological protein S, as free (PS-f), and in reversible complex with C4b-binding protein as well as functional protein C (PC) in a homogeneous group of 20 young healthy women. The participants were randomly given either gestodene (75 micrograms) or desogestrel (150 micrograms) in combination with ethinyl oestradiol (30 micrograms). Blood samples were taken prior to the initiation of the treatment and at the end of the sixth 21-day treatment cycle. The mean concentration of both free and bound PS fell significantly, the decrease still being within the reference range. Conversely, the plasma values for PC rose to a statistically significant extent. There were no significant differences between the two OCs. Hypothetically, the changes in PS-f (active fraction) might be conducive to a procoagulant state, which the increased PC may compensate. The reverse effect of two OCs on the activity of the protein C-protein S anticoagulant system might suggest a different regulation of their synthesis.

Adult↗
PubMed1989

Glucose and insulin levels after six months of treatment with a triphasic oral contraceptive containing ethinyl estradiol and norethindrone.

A prospective study of carbohydrate metabolism was done on 33 women who used a triphasic oral contraceptive (OC) containing ethinyl estradiol and norethindrone for six months. A three-hour oral glucose tolerance test was administered before and after the OC usage, and both the blood glucose and insulin levels were determined. A significant decrease in the fasting glucose level was found with treatment. All other glucose values and insulin levels were unchanged.

Adult↗
PubMed1989

Clinicopathological problems of the local tissue effect of IUDs containing copper. III. Cytochemical study of the endometrial scrapings.

The clinicopathological problems of the tissue effect of copper-containing IUDs are discussed. In the third part of their series, authors present the cytochemical analysis of the endometrial scrapings. For the investigations, dithizone, salicylaldoxime, rubeanic acid as well as dimethylglyoxime were used. The reaction precipitate, the copper dithizone complex, could be visualized partly intracellularly and intramitochondrially and partly interstitially. The technical problems of copper demonstration are also dealt with.

Copper↗
PubMed1986

Antacid does not reduce the bioavailability of oral contraceptive steroids in women.

The bioavailability of contraceptive steroids was studied in 12 women who were given an antacid and a contraceptive pill simultaneously. They were given a single pill containing ethinyl estradiol (EE2) 30 micrograms in combination with either norethisterone (NET) acetate 1 mg (n = 6), or levonorgestrel (LNg) 150 micrograms, (n = 6). Blood samples were collected up to 24 hours. Four weeks later the same pill was administered along with a single tablet of antacid (magnesium trisilicate 0.5 g and dried aluminum hydroxide 0.25 g) and blood samples were collected as before. Serum levels of NET, LNg and EE2 were measured by radioimmunoassay. No effect of antacid administration on bioavailability of any contraceptive steroid was observed as judged by peak levels and areas under concentration-time curve (AUC). Incidentally, significantly higher serum concentrations of EE2 were observed when it was administered in combination with NET than with LNg. The possible reasons for this finding are discussed.

Adult↗