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PubMed1986

Use of oral contraceptives by women with epilepsy.

Oral contraceptives have not been associated with exacerbation of epilepsy despite warnings in package inserts. No clinical study has provided scientific evidence of worsening of seizures in epileptic women who use oral contraceptives, and improvement in seizure control has occurred in some cases. The main concern about use of oral contraceptives in this population is their effectiveness in preventing conception. Failure rates are higher in groups of women taking enzyme-inducing antiepileptic drugs. The degree of increased metabolism of estrogen and progestin components is highly variable and unpredictable among individuals. Use of higher doses increases protection against conception but also increases the risk of side effects, particularly in patients in whom no enzyme induction occurs. The strength of hormones in the pill should be selected individually when initiating use. Some women may require higher doses for full contraceptive effect.

Animals↗
PubMed1997

[A case of arterial hypertension after use of oral contraceptives].

It is known that oral contraceptives may induce high blood pressure that usually returns to normal values a few weeks after interruption of the drugs, and without any specific treatment. The precise mechanism by which oral contraceptives cause hypertension is not clear. A severe hypertension and mild heart failure in a young woman using oral contraceptives has been observed in the case described. The patient needed a careful and prolonged therapy to maintain a normal blood pressure.

Adult↗
PubMed1998

Epidemiology of oral contraceptives and cardiovascular disease.

PURPOSE: To review the association between combined oral contraceptives and cardiovascular disease, with emphasis on oral contraceptives containing low doses of estrogen (low-dose oral contraceptives). DATA SOURCES: A systematic search of the MEDLINE database was done for all relevant articles published between 1967 (when low-dose oral contraceptives were introduced in the United States) and June 1997. Textbooks, meeting proceedings, and reference lists were also searched. STUDY SELECTION: All English-language human epidemiology studies of oral contraceptives that used cardiovascular disease as an end point were reviewed. Animal and metabolic studies were reviewed only if they were especially relevant to the mechanism of action of oral contraceptives. DATA EXTRACTION: Descriptive and analytic data from each study were collected. DATA SYNTHESIS: Data were organized by cardiovascular end point, study design, estrogen dose, and type of progestogen. Data on relative and absolute risk are presented to address current prescription guidelines. CONCLUSIONS: The risk for cardiovascular disease is lower with current preparations of oral contraceptives, including those that contain the new progestogens, than with older oral contraceptives containing high doses of estrogen. Among users of low-dose oral contraceptives, cardiovascular diseases occur mainly in smokers and women with predisposing factors. Every effort should be made to encourage smoking cessation among potential users of oral contraceptives.

Animals↗
PubMed1984

Colonic Crohn's disease and use of oral contraception.

The prevalence of use of oral contraception before the onset of disease was established in 100 consecutive women attending follow up clinics for inflammatory bowel disease. A significant excess of women with Crohn's disease confined to the colon had taken oral contraceptives in the year before developing symptoms (10/16 (63%] compared with women with small-intestinal Crohn's disease (12/49 (24%); p less than 0.02) and women with ulcerative colitis (3/35 (9%); p less than 0.0005). When the patient groups were matched for age and year of onset of disease usage of oral contraception before the onset of disease was still more common among women with isolated colonic Crohn's disease (9/12, 75%) than among those with ulcerative colitis (2/12 (17%); p less than 0.02) and was also more common than would be expected from reported figures for oral contraception in England and Wales (31.4% of women aged under 41; p less than 0.005). A survey of current patient records showed that isolated colonic disease was at least twice as common among women with Crohn's disease (63/218, 29%) compared with men (25/181, 14%; p less than 0.001). These data support the suggestion made previously that oral contraceptives may predispose to a colitis that resembles colonic Crohn's disease.

Adolescent↗
PubMed1979

[Oral contraception with an associated therapeutic action using a progestational method at two levels (author's transl)].

The authors, basing their work on their experience over many years with a large number of cases, are proposing that synthetic progestational agents can be used at two levels of dosage, to serve as contraception and as a treatment when a progestational agent is used and is followed by micro-dosages of another progestational substance. So they prescribe at the end a of cycle following different dosages for different lengths of time, the same (or a different) progestational agent to treat breast troubles or menstrual troubles which are often intricate, particularly near the menopause. The authors in this way can compare by trials the effects of this method as compared with those of a progestational contraceptive administered in high doses and prescribed in an interrupted way and the prescription of micro-dosages of progestational agents that are taken "non-stop" which is now a classical method of treatment. This new method of contraception using progestational agents at two levels of dosage is particularly useful in patients who cannot take oestrogens because of metabolic upsets or because of tumours and who have reacted badly to the two other methods mentioned. If the dose, which can be calculated thanks to our knowledge of the hormonal background of the patient, is altered good therapeutic results and a relatively sure method of contraception is evolved without metabolic risks for the patient. This association of two progestational levels of dosage seems to be indicated particularly in women of over 40 years of age.

Adult↗
PubMed1998

A randomized cross-over study on various hormonal parameters of two triphasic oral contraceptives.

The effect of two triphasic oral contraceptives (Triquilar [TRQ] and Trisiston [TRS]) containing ethinyl estradiol (EE) and levonorgestrel (LNG) on various hormonal parameters was investigated in 26 women during a cross-over study. TRS consisted of 0.03 mg EE + 0.05 mg LNG (six tablets), 0.04 mg EE + 0.075 mg LNG (six tablets), and 0.03 mg EE + 0.15 mg LNG (nine tablets), whereas TRQ was different in the second phase (five tablets) and third phase (10 tablets). Blood samples were taken on days 6, 11, 21, and 28 of the control and washout cycles and the third treatment cycle. Both formulations inhibited ovulation reliably and decreased the serum levels of gonadotropins, free testosterone, and dehydroepiandosterone sulfate in a time-dependent manner, whereas estradiol and testosterone were already suppressed on day 6, indicating a direct suppressive effect on ovarian steroid synthesis. Prolactin, which rose sporadically in some women, was not significantly changed. In contrast, the levels of sex hormone binding globulin, corticosteroid binding globulin, and cortisol were significantly elevated by 100%. During the hormone-free interval of 7 days, all parameters returned at least partly to baseline. There was no significant difference between the effects of both formulations. The results suggest the possibility of a direct inhibitory effect of contraceptive steroids on ovarian steroid synthesis.

Adult↗
PubMed1995

Oral contraceptives and venous thromboembolism: a quantitative discussion of the uncertainties.

OBJECTIVES: The majority of post-thrombotic women are barred from using oral contraceptives. We evaluated this policy for its clinical relevance. DESIGN: A meta-analysis of controlled studies between 1960 and 1993. SETTING: A Medline computer search, from 1966 to 1993, in multiple languages, with the following index terms: thrombosis, thrombopheblitis, vein, venous, pulmonary embolism, contraceptives, oestrogen, oral. STUDY SELECTION: A total of 588 articles or abstracts were reviewed for controlled studies, in which an index group was compared with a control group. Included were one randomized trial, six follow-up studies and eight case-control studies. MAIN OUTCOME MEASURES: Summary thrombosis risk for oral contraceptive users, number needed to discontinue oral contraceptives to prevent one (recurrent) thrombosis, comparison of additional unwanted pregnancies and postpartum thrombosis between alternative birth-control methods. RESULTS: The studies proved highly heterogeneous with regard to size and direction of the risk estimate. The summary relative risk of first thrombosis during oral contraceptive use was 2.9 (95% CI, 0.5-17). Since the risk of thrombosis recurrence is not well known, we estimated alternatives, making various hypothetical assumptions, wherein women would continue to take oral contraceptives after a first episode of thrombosis, or stop and switch to use of an intra-uterine device, condom or the progestogen-only pill. Depending on the assumptions with regard to recurrence risk and the existence of possible subgroups with genetic coagulation defects, the cost-benefit ratio of advising against the use of oral contraceptives after a first thrombosis varied tremendously. CONCLUSIONS: Our analysis shows that we lack the necessary data for recurrence risk of venous thrombosis during continuing use of oral contraceptives, or after switching to other modes of contraception. This reflects the clinical uncertainties that result in highly contradictory advice to young women who have experienced a first thrombosis. Only follow-up studies on recurrence risk will settle the issue.

Adolescent↗
PubMed1993

Oral contraceptives for the prevention of osteoporosis.

Oral contraceptives are a safe and acceptable form of contraception in perimenopausal women and may be effective in maintaining bone mass prior to menopause. Studies of the bone-sparing properties of oral contraceptives are difficult to interpret because of confounding variables, such as age, smoking, duration of use, exercise, menstrual function and endocrine diseases. Nevertheless, the results of many studies suggest that premenopausal use of oral contraceptives is associated with higher bone density than is nonuse. Long-term premenopausal oral contraceptive use allows women to enter menopause with bone density that is 2-3% higher than in nonusers. The optimal duration of use and dosage of estrogen and the clinical importance of this effect remain to be determined.

Adolescent↗
PubMedDate not supplied

[Social psychological and sexological aspects of oral contraception (author's transl)].

An inventory is made on the hindrances to the acceptance of contraception in general and oral contraception in particular. They are grouped as hindrances related to the social and psychological significance of "making children", hindrances related to the social and psychological significance of "having children" hindrances, related to the method of oral contraception itself, to be divided in social hindrances, psychological hindrances and medical hindrances and finally hindrances related to the provision of the pill to the individual user. Each of these is amply discussed, the author expresses the hope that by identification of these hindrances, lessons may be learned for the future, when other methods of contreception become available.

Contraception↗
PubMed1979

Do anticonvulsants reduce the efficacy of oral contraceptives?

Women in our area with epilepsy who were also taking oral contraceptives were identified. Of 82 patients taking oral contraceptives, 41 had used both anticonvulsants and oral contraceptives for a total of 955 months. Three documented oral contraceptive (pill) failures occurred during this period, whereas the expected number of 0.12 (relative risk, 25; 95% confience interval, 5 to 73). No pill failures were observed in 2,278 months among women with epilepsy who were taking oral contraceptives but who were not taking anticonvulsants at this time. Thus our data support the suggestion that there is an increased rate of pill failure among women taking anticonvulsants. In view of this diminished effectiveness, the advisability of using oral contraceptives rather than one of the other forms of contraception when anticonvulsant medication is being used concurrently may need to be reevaluated.

Anticonvulsants↗
PubMed1989

Combined oral contraceptives and gallbladder cancer. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives.

The relationship between combined oral contraceptives and primary gallbladder cancer was examined in 58 cases and 355 controls participating in an international hospital-based, case-control study. Use of combined oral contraceptives at any time was not associated with the risk of developing gallbladder cancer (RR = 0.6, 95% Cl 0.3, 1.3), and no clear patterns of risks were observed according to the duration of use, or time since first or most recent use. There was also no evidence that oral contraceptives effected risk of gallbladder cancer in women with or without a prior history of gallbladder disease. A history of gallbladder disease or gallstones was a strong risk factor for gallbladder cancer (RR = 2.3,95% Cl 1.2,4.4).

Adult↗
PubMed1999

Importance of levonorgestrel dose in oral contraceptives for effects on coagulation.

Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and resemble third-generation contraceptives.

Activated Protein C Resistance↗
PubMed1998

Myocardial infarction and stroke in young women: what is the impact of oral contraceptives?

Recent discussions have centered on the small apparent risk increase for venous thromboembolism found with newer oral contraceptives (third-generation oral contraceptives containing the progestins desogestrel and gestodene) compared with older oral contraceptives (second-generation). This article reviews the studies addressing the association between oral contraceptive use and thromboembolic conditions affecting the arterial system, ischemic stroke, and myocardial infarction. Differences are found between a US database study, which showed no risk of ischemic stroke or myocardial infarction associated with low-dose oral contraceptive use, and the European studies, which showed oral contraceptive use in general to be associated with increased risks of ischemic stroke and myocardial infarction. The European studies showed no difference between oral contraceptive generations with respect to the occurrence of ischemic stroke; however, the risk of myocardial infarction associated with oral contraceptive use was consistently lower for third- than for second-generation oral contraceptives. Although there seems to be no differential risk of ischemic stroke associated with oral contraceptive generations, third-generation oral contraceptives appear to be consistently associated with no excess risk of myocardial infarction. In all instances, however, cardiovascular risk factors other than oral contraceptive use play the predominant role in the occurrence of ischemic stroke and myocardial infarction.

Adolescent↗
PubMed1989

Oral contraceptives: a reassessment.

Cardiovascular risks attributable to oral contraceptive use may now be subdivided into those that appear to be secondary to the estrogen component, i.e., venous thrombosis, pulmonary embolism, and those linked to the progestin component, i.e., small vessel disease including myocardial infarction and cerebrovascular accident. It appears that venous risk is attributable to subtle changes in clotting factors, while arterial risk may be secondary to changes in glucose and lipid metabolism. In order to determine which women are at greatest risk from oral contraceptive use, Spellacy et al. has developed a risk scoring form that aids in the screening process. After excluding women with an absolute contraindication to pill use, women at greatest risk for cardiovascular disease related to oral contraceptive use are those with a family history of hyperlipidemia, gestational or overt diabetics, hypertensives, and smokers over the age of 35. The gradual reduction by manufacturers of the steroid content of oral contraceptives appears to have lessened the incidence of adverse effects. Our current knowledge of risk factors permits the clinician to reduce exposure to oral contraceptive-related mortality by as much as 86 per cent. As we continue to search for ways to reduce risk among oral contraceptive users, it is important to note that more than 25 per cent of women are still taking formulations containing 50 micrograms of estrogen. It becomes the responsibility of the practicing physician to "step-down" these patients to lower-dose preparations such as the multiphasics. Such preparations also represent optimal therapy for first-time pill users.

Contraceptives, Oral↗
PubMed1977

Endometrial carcinoma and oral contraceptive agents.

Six patients who took oral contraceptive agents for 5 to 18 years developed endometrial neoplasia. Endometrial adenocarcinoma occurred in 4 of these patients and severe adenomatous hyperplasia occured in 2. Five of the 6 patients took sequential agents; 1 patient used a combined agent. An additional patient who took Premarin and Provera sequentially developed adenocarcinoma of the endometrium. Eighteen cases of endometrial adenocarcinoma and 7 cases of adenomatous hyperplasia in patients with long-term sequential oral contraceptive use have previously been reported by others. Progestogens may not be completely protective against the endometrial cancer-causing potential of the estrogens, especially in the sequential regimens.

Adenocarcinoma↗
PubMed1991

Oral contraceptives and neoplasia of the ovary.

Epidemiologic literature on oral contraceptives in relation to primary ovarian cancer is reviewed. Compared to women who have never used oral contraceptives, women who have ever taken oral contraceptives have about a 30% reduction in risk for epithelial ovarian cancer, and five or more years of use is associated with a 50% reduction in risk. The protective effect of oral contraceptives persists for ten or more years after use is discontinued, and becomes apparent several years after beginning use. Effects of oral contraceptives are similar for malignant and borderline malignant epithelial ovarian cancer. Reduced risks among oral contraceptive users have been observed for all major histologic subtypes of epithelial ovarian cancer, and for women from developed and developing countries. Risk estimates for epithelial ovarian cancer in relation to oral contraceptive use stratified by age at diagnosis or parity are not uniform across studies. No consistent protective effect is apparent for non-epithelial ovarian tumors or benign ovarian tumors, including teratomas and cystadenomas, although limited data are available on the relationship between oral contraceptives and these neoplasms. Several areas for future research are described.

Contraceptives, Oral↗
PubMed1980

Measurement by isotope dilution mass spectrometry of 17 alpha-ethynyloestradiol-17 beta and norethisterone in serum of women taking oral contraceptives.

The highly specific and accurate technique of isotope dilution mass spectrometry has been used for the measurement of 17 alpha-ethynyloestradiol-17 beta and norethisterone in serum. Serum samples were obtained from female volunteers who received 2.5 mg lynestrenol and 50 micrograms 17 alpha-ethynyloestradiol-17 beta in two different galenical preparations. The determination of total 17 alpha-ethynyloestradiol-17 beta (conjugated and non-conjugated) was carried out by the following procedure: (1) adsorption of the steroids from 1 ml serum to Amberlite XAD-2; (2) enzyme hydrolysis of the conjugated steroid; (3) addition of 1 ng [6,7-3H2] 17 alpha-ethynyloestradiol-17 beta as internal standard; (4) column chromatography on Sephadex LH 20; (5) derivative formation with heptafluorobutyric anhydride; (6) isotope dilution mass spectrometry at m/z 474 and 478 using a glass capillary gas-liquid chromatography column. For the measurement of norethisterone, which is the major metabolite of lynestrenol, 1 ng [7-3H]norethisterone was added to 0.5 ml serum. The labelled and the non-labelled steroids were extracted and purified by column chromatography on Sephadex LH 20. The norethisterone was reacted to form the 3-enol-17 beta-trimethylsilyl ether of norethisterone and [3H]norethisterone. For isotope dilution mass spectrometry the derivative was injected into the glass capillary column which was coupled to the mass spectrometer. The instrument was adjusted to m/z 442 and 444, corresponding to the molecular ions of the ether derivatives of norethisterone and [7-3H]norethisterone. Accuracy was achieved by the use of highly specific technique of mass spectrometry and the exact control of recovery using the isotope dilution principle. The precision was 4.5% (CV) for the determination of 17 alpha-ethynyloestradiol-17 beta and 2.5% (CV) for norethisterone. The lower limit of detection was at 20 pg ml-1 for both methods.

Contraceptives, Oral↗