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At least 19 recordsLinked to original sources
PubMed1995

European Society of Contraception oral contraceptives survey update: birth control methods in "Europe of the 12".

The European Society of Contraception developed a survey to examine birth control methods in the 12 countries++ of the European Community. Responses to those questions relating to prescribing++ practices of oral contraceptives (OCs) are presented herein. The survey was sent to 400 physicians. One hundred two responded, most from France, Belgium, and the United Kingdom. The responses revealed that the most popular OCs are modern combined formulations containing low doses of ethinyl estradiol and progestogens such as norgestimate, desogestrel, gestodene, and levonorgestrel. More than half of physicians prescribe a particular formulation because of its tolerability and 20% because of its hormonal content. More than 90% prescribe OCs to healthy, nonsmoking women over 40. However, three fourths will not prescribe OCs to smokers over 35. Half of physicians recommend mammography for their older OC patients. Half also recommend cholesterol screening, but 8% only for women over 30. Most physicians are no longer reluctant to prescribe OCs to their diabetic patients: 61% prescribe OCs for women with non-insulin-dependent diabetes, 56% for those with insulin-dependent diabetes, and 85% for those with a history of gestational diabetes. Despite recent studies showing no relation between past OC use and cardiovascular disease, 42% of physicians said that their greatest OC-related health concern is cardiovascular disease. One third cited noncompliance as their greatest concern. These results reveal inhomogeneous prescribing practices for OCs among European physicians. ¿Over-screening¿--not prescribing the pill because of perceived (but not necessarily real) health risks--may be depriving many women of the contraceptive and noncontraceptive benefits of OCs. Complete and accurate information--as promoted by the European Society of Contraception--is one way to combat such overscreening.

Adult↗
PubMed1990

Pharmacokinetic drug interactions with oral contraceptives.

Oral contraceptive steroids are used by an estimated 60 to 70 million women world-wide. Over the past 20 years there have been both case reports and clinical studies on the topic of drug interactions with these agents. Some of the interactions are of definite therapeutic relevance, whereas others can be discounted as being of no clinical significance. Pharmacological interactions between oral contraceptive steroids and other compounds may be of 2 kinds: (a) drugs may impair the efficacy of oral contraceptive steroids, leading to breakthrough bleeding and pregnancy (in a few cases, the activity of the contraceptive is enhanced); (b) oral contraceptive steroids may interfere with the metabolism of other drugs. A number of anticonvulsants (phenobarbital, phenytoin, carbamazepine) are enzyme-inducing agents and thereby increase the clearance of the oral contraceptive steroids. Valproic acid has no enzyme-inducing properties, and thus women on this anticonvulsant can rely on their low dose oral contraceptive steroids for contraceptive protection. Researchers are now beginning to unravel the molecular basis of this interaction, with evidence of specific forms of cytochrome P450 (P450IIC and IIIA gene families) being induced by phenobarbital. Rifampicin, the antituberculous drug, also induces a cytochrome P450 which is a product of the P450IIIA gene subfamily. This isozyme is one of the major forms involved in 2-hydroxylation of ethinylestradiol. Broad spectrum antibiotics have been implicated in causing pill failure; case reports document the interaction, and general practitioners are convinced that it is real. The problem remains that there is still no firm clinical pharmacokinetic evidence which indicates that blood concentrations of oral contraceptive steroids are altered by antibiotics. However, perhaps this should not be a surprise, given that the incidence of the interaction may be very low. It is suggested that an individual at risk will have a low bioavailability of ethinylestradiol, a large enterohepatic recirculation and gut flora particularly susceptible to the antibiotic being used. Two drugs, ascorbic acid (vitamin C) and paracetamol (acetaminophen), give rise to increased blood concentrations of ethinylestradiol due to competition for sulphation. The interactions could have some significance to women on oral contraceptive steroids who regularly take high doses of either drug. Although on theoretical grounds adsorbents (e.g. magnesium trisilicate, aLuminium hydroxide, activated charcoal and kaolin) could be expected to interfere with oral contraceptive efficacy, there is no firm evidence that this is the case. Similarly, there is no evidence that smoking alters the pharmacokinetics of oral contraceptive steroids. These agents are now well documented as being able to alter the pharmacokinetics of other concomitantly administered drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2001

Biphasic versus monophasic oral contraceptives for contraception.

OBJECTIVES: To compare biphasic oral contraceptives with monophasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. Our a priori hypotheses were: (a) biphasic oral contraceptives are less effective in preventing pregnancy than are monophasic oral contraceptives, and (b) biphasic oral contraceptives cause more side effects, give poorer cycle control, and have lower continuation rates. SEARCH STRATEGY: We searched computerized databases MEDLINE, EMBASE, Popline and the Cochrane Controlled Trial Register. Additionally we searched the reference lists of all potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the U.S. SELECTION CRITERIA: We included randomized controlled trials comparing any biphasic oral contraceptive with any monophasic oral contraceptive when used to prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found during the various literature searches for possible inclusion and assessed their methodological quality using the Cochrane guidelines. We contacted the authors of all included studies and of possibly randomized studies for supplemental information about the study methods and outcomes. We entered the data in RevMan 3.1, imported the data into RevMan 4.1, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding, and study discontinuation due to intermenstrual bleeding. MAIN RESULTS: Only one trial of limited quality compared a biphasic and monophasic preparation. Percival-Smith et al. (1990) examined 533 user cycles of a biphasic pill (norethindrone 500 mcg/ethinyl estradiol 35 mcg for ten days, followed by norethindrone 1000 mcg/ethinyl estradiol 35 mcg for eleven days; Ortho 10/11) and 481 user cycles of a monophasic contraceptive pill (norethindrone acetate 1500 mcg/ethinyl estradiol 30 mcg daily; Loestrin). The study found no significant differences in intermenstrual bleeding, amenorrhea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. REVIEWER'S CONCLUSIONS: Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial, and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

Contraception↗
PubMed1989

Idiopathic thromboembolism associated with triphasic oral contraceptives.

Oral contraceptives are one of the most effective and widely used of the reversible contraceptive methods. Thromboembolic disease associated with the use of oral contraceptives has been widely reported. In recent years, attempts to understand the pathogenesis of oral contraceptive-induced thromboembolic disease have found a correlation between larger estrogen doses and increased risk for a thrombotic event. Because the newer triphasic oral contraceptives provide effective contraception with a method of administration that mimics normal hormonal fluctuations during the menstrual cycle, some prescribers may infer that these products are associated with a decreased incidence of adverse effects over alternative oral contraceptives. We present two cases of idiopathic thromboembolism associated with the use of a triphasic oral contraceptive with a discussion of the proposed pathogenic mechanisms for these events.

Adult↗
PubMed1996

[Significance of hereditary thrombophilia for risk of thrombosis with oral contraceptives].

Oral contraceptives increase the natural incidence of venous thromboses of 1-2/10,000 women per year 3-to 4fold. Recent investigations have shown that during intake of desogestrel or gestodene containing formulations the risk is twice that with older low-dose ovulation inhibitors. This difference is larger in first time users than in women who had previously used an oral contraceptive. During pregnancy, the incidence of thromboses rises up to 10/10,000 women-years and post partum up to 40/10,000 women-years. In about 60 % of thromboses no causal explanation can be found. It is suggested that in 40 % of all cases an inherited thrombophilia is present. Among the hereditary types of thrombophilia, the resistance against activated protein C (APC-resistance) represents nearly 50 %, while altogether 15 to 20 % is based on a deficiency of antithrombin III, protein C or protein S. APC-resistance the prevalence of which is 3-5 % in the general population, increases the risk of thrombosis 8fold and in users of oral contraceptives 35fold. Protein C-deficiency (prevalence 0.1-0.5 %) increases the risk of thrombosis 9fold and in users of oral contraceptives 15fold, while antithrombin III-deficiency (prevalence 0.02-0.05 %) enhances the risk in pill-users 8fold. Ovulation inhibitors do not influence risk of thrombosis in women with protein S-deficiency. Antiphospholipid-antibodies the concentration of which may increase during treatment with oral contraceptives, represent a considerably enhanced risk of thrombosis, too. A positive family history (before age of 40 years) indicates an inherent thrombophilia. In these risk groups, the cost/benefit ratio of a selective screening is unfavorable, as at most 70 % of the hereditary thrombophilias can be diagnosed by laboratory analysis, and only very few patients will actually experience a thrombotic event: only 3 of 1000 carriers of APC-resistance will suffer from thrombosis during oral contraception per year. On the other hand, a negative result of laboratory tests does not exclude a hereditary thrombophilic disorder which as yet cannot be substantiated. It is not yet clarified whether a selective screening is superior to a careful assessment of individual and family history. A general screening cannot be justified because of the unfavorable cost/benefit ratio. If the individual or family history or pathological laboratory parameters indicate an enhanced risk of thrombosis, this risk has to be carefully weighed against the consequences of discontinuation of pill use. Those few individuals with risk factors who will experience a thrombosis, cannot be identified in advance. If in patients with thrombophilic disorders and/or other risk factors the use of oral contraceptives represents a particularly high risk, other contraceptive methods should be taken into consideration. If a patient with risk factors decides for the use of oral contraceptives, she has to be informed that in the case of symptoms indicating a thrombosis, the physician has to be consulted immediately. The earlier an appropriate therapy is initiated, the more effectively an acute pulmonary emboli or permanent damages, e.g. the post-thrombotic syndrome, can be prevented.

Adult↗
PubMed1994

Effect of oestrogen dose on whole blood platelet activation in women taking new low dose oral contraceptives.

Oral contraceptive use is known to cause changes in the haemostatic system. These changes are thought to be related to oestrogen dose and to provide a possible link between the increased risk of thromboembolic disease known to occur in women taking oestrogen containing oral contraceptives. This study measured whole blood platelet activation, serially, in women taking oral contraceptives containing 20 micrograms and 30 micrograms ethinyloestradiol combined with desogestrel. Increased levels of ADP and arachidonic acid induced aggregation were observed in women taking the 30 micrograms ethinyloestradiol combination. Platelet release of beta-thromboglobulin (beta TG) was also significantly increased. Increased collagen induced aggregation was observed but this failed to reach statistical significance for the individual treatment groups. In women taking the 20 micrograms ethinyloestradiol combination, a significant increase was only observed when platelets were stimulated with arachidonic acid. Platelet factor 4 (PF4) levels were unchanged in both groups. Significantly higher levels of beta TG were observed in women taking the 30 micrograms ethinyloestradiol combination compared with women taking the 20 micrograms ethinyloestradiol combination. These results show that oral contraceptive use is associated with platelet activation. Women taking the 20 micrograms ethinyloestradiol combination show less changes in platelet activation than women taking the 30 micrograms ethinyloestradiol combination. This lower dose pill may therefore be particularly suitable for high risk women wishing to use oral contraception.

Adolescent↗
PubMed1976

Potencies of oral contraceptives.

Oral contraceptives are combinations of estrogens and progestogens or, in the case of the mini-pills, progestogens alone. With specific test procedures in laboratory animals or human subjects, it is possible to assign potency evaluations to the components relative to the progestational, estrogenic, or antiestrogenic activities of the progestogen or to the estrogenic potencies of the estrogenic component. It might even be possible to quantify the synergistic effects of the estrogen on the progestational agent. Unfortunately, however, it is impossible now to amalgamate such assay results into single estimates of the potencies of the combinations (either the combination products per se or the combination tablets of sequential products). For example, an over-all estrogenic potency of a combination preparation would involve the integration of contributions form the estrogen itself plus the estrogenic products of metabolism of the progestogen minus the antagonistic effect of the progestational agent, if any. These factors cannot now be quantified independently, much less merged into a single figure of clinical significance. Further, even if it were possible to produce such an estimate, it is unlikely that the evaluation would be meaningful in relation to any putative side effect or adverse reaction, i.e., the alleged thrombogenic effects of oral contraceptives cannot currently be related directly to any measure of potency that will allow prediction of these clinical conditions from laboratory models. Any evaluation of the potential of a given contraceptive to produce a specific side effect will depend upon data generated with specific regard to that adverse reaction and the individual product in question.

Contraceptives, Oral↗
PubMed1990

Long-term experience with a low-dose oral contraceptive.

Oral contraception has proved to be the most efficient reversible method of fertility control for over 25 years. During this period, various investigations and epidemiological studies have suggested that some risks may be involved, but, on the other hand, a number of non-contraceptive benefits have become obvious. The results of these investigations were taken into account when new formulations had to be developed, with an aim to improving hormonal fertility control with regard to its tolerance, cycle control, and impact on metabolism. Since then, the objective of research has been to contrive new hormonal contraceptives which ensure safety to the largest possible extent, from a medical point of view, for the sake of the patient, without affecting contraceptive effectiveness. The aim to reduce side-effects connected with the use of oral contraception, as well as to lower the risks possibly involved, has obviously been achieved by extensive research. Both by devising a new substance and reducing doses, the criteria of modern low-dose oral contraception have been met, as has become evident in the course of the clinical experience gathered with Femovan.

Acne Vulgaris↗
PubMed1992

Serum bile acids and the bile acid tolerance test under oral contraception.

Oral contraceptives (OC) have lithogenic properties as shown by a rise in biliary cholesterol secretion and cholesterol saturation index. Since we noted not only a rise in saturation index, but also a reduction in chenodeoxycholate (CDC) pool size and an increase in cholate (C) pool size during oral contraception (30 micrograms ethinylestradiol + 150 micrograms desogestrel), we investigated the endogenous bile acid tolerance test as a potential predictor of this effect on bile acid pool sizes using a cholecystokinin infusion of 55 min duration (1.2 U.kg-1.hr-1) as stimulus of the enterohepatic bile acid circulation in 12 healthy females before and during oral contraception for 3-5 months. Serum C and CDC conjugates were measured at 5-10 min intervals over a period of 150 min and analysed by two specific RIA's. Although no significant correlations between the serum CDC and C measurements and CDC and C pool sizes were found, a significant reduction of nearly 40% for both serum peak levels and the integrated area under the serum curve of CDC conjugates during oral contraception, but not of C conjugates was found. The reduction in serum levels of CDC conjugates during OC using the present model is best explained by both a reduction in CDC pool size and more efficient hepatic uptake of CDC conjugates (consisting of considerably more taurine conjugates during OC use), as well as by an intestinal effect on bile acid absorption under OC.

Adult↗
PubMed1987

Phasic approach to oral contraceptives.

Oral contraceptives were initially very high in estrogen and progestogen and had a uniform dosage schedule throughout the entire cycle. These early oral contraceptives were associated with high rates of side effects and complications. As a result, the hormone levels have been gradually reduced to attain the minimal amount necessary for contraception while most of the undesired side effects and complications have been eliminated. Recently, a new approach has been added. This mechanism consists of altering the dose of estrogen or progestogen or both during the month and is referred to as the phasic approach. The newest phasic pills now use a triphasic approach. Three basic formulations of the triphasic pill have been developed. In two of the three formulations, the progestogen level is altered, whereas the estrogen level remains stable; in the third formulation, both estrogen and progestogen are changed. Multiple clinical studies of the triphasics, such as ethinyl estradiol and levonorgestrel, prove that there is a significant reduction in the incidence of side effects and complications related to oral contraception.

Contraceptives, Oral, Combined↗
PubMed1988

Liver tumor in long-term user of oral contraceptives.

Oral contraceptives are implicated in the development of some liver tumors. Paralleling the widespread use of these drugs has been an increase in reported cases of hepatic cell adenomas. Large, multiple tumors, often manifested by spontaneous rupture and hemoperitoneum, have been associated with prolonged use of oral contraceptives. When use of oral contraceptives is discontinued, the hepatic cell adenoma regresses.

Adult↗
PubMed1995

[Pharmacology of oral contraceptives].

Oral contraceptives include two types of steroids; ethinyl-estradiol as the main estrogenic component which dose vary from 20 to 50 micrograms per tablet (mostly 30 to 35 micrograms) and progestins essentially derivatives of 19 nortestosterone. Derivatives of 19 norprogesterone such as nomegestrol acetate or ST 1435 are not used as oral contraceptives but are being evaluated through parenteral administration, e.g. implants or transdermal systems. The assessment of the pharmacological properties of these progestins indicate a high antigonadotropic and a high antiestrogenic properties for levonorgestrel and for the newer gestagens as well. Therefore very low doses are being used in the current oral contraceptives. However, there is a lower margin of security with the low dose contraceptives than with previous standard combinations and especially when concomitant medications are ingested such as enzyme-inducing agents. Selection of contraceptive methods should be discussed when specific co-medications are necessary.

Contraceptives, Oral, Synthetic↗
PubMed2001

Progesterone receptor variant increases ovarian cancer risk in BRCA1 and BRCA2 mutation carriers who were never exposed to oral contraceptives.

Oral contraceptives have been shown to be protective against hereditary ovarian cancer. The variant progesterone receptor allele named PROGINS is characterized by an Alu insertion into intron G and two additional mutations in exons 4 and 5. The PROGINS allele codes for a progesterone receptor with increased stability and increased hormone-induced transcriptional activity. We studied the role of the PROGINS allele as a modifying gene in hereditary breast and ovarian cancer. The study included 195 BRCA1 and BRCA2 carriers with a prior diagnosis of ovarian cancer, 392 carriers with a diagnosis of breast cancer and 249 carriers with neither cancer. Fifty-eight women had both forms of cancer. Five hundred and ninety-five women had a BRCA1 mutation and 183 women had a BRCA2 mutation. Overall, there was no association between disease status and the presence of the PROGINS allele. Information on oral contraception use was available for 663 of the 778 carriers of BRCA1 or BRCA2 mutations. Among the 449 subjects with a history of oral contraceptive use (74 cases and 365 controls), no modifying effect of PROGINS was observed [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.5-1.3]. Among the 214 carriers with no past exposure to oral contraceptives, the presence of one or more PROGINS alleles was associated with an OR of 2.4 for ovarian cancer, compared to women without ovarian cancer and with no PROGINS allele (P = 0.004; 95% CI 1.4-4.3). The association was present after adjustment for ethnic group and for year of birth.

Adult↗
PubMed1985

[Hair loss during treatment with oral contraceptives].

Oral contraceptives with a dominant androgen component can cause or worsen androgen-dependent alopecia in women. This diagnosis can only be made if other causes of alopecia (which can occur at the same time as treatment with oral contraceptives) have been excluded. The patient's endocrine profile must be investigated sometimes, this being in order to detect any excess production of androgens. These types of alopecia call for the stopping of the oral contraceptive and sometimes also calls for oral anti-antigen treatment.

Alopecia↗
PubMed1976

A current appraisal of side effects of oral contraceptives.

Oral contraception, although offering almost 100 per cent protection against pregnancy, is associated with many side effects which have resulted in much unnecessary adverse publicity. Such side effects, the majority of which are of annoying nature only, are due to the synthetic hormones used, and have resulted in many changes in formulation and in the withdrawal of several preparations. The types of preparations available are discussed and the side effects appraised from both the patient's and the physician's viewpoint.

Abnormalities, Drug-Induced↗