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Chorea induced by oral contraceptives.

A rare complication of oral contraceptive therapy is the induction of chorea. We here describe five cases of chorea in patients receiving low- or high-dose estrogen-containing contraceptives. All patients were nulliparous, young (average age 19 years), and became symptomatic shortly (average of 5 weeks) after initiation of contraceptive therapy. Two patients previously suffered an episode of Syndenham chorea; one experienced chorea in the course of Henoch-Schönlein purpura; and two had a history of congenital cyanotic heart disease without chorea. Dyskinesia resolved in all patients upon discontinuing the medication. Patients with preexisting striatal abnormalities appear more susceptible to oral contraceptive-induced chorea which is reversible on drug discontinuation. The mechanism of oral contraceptive-induced chorea is unknown, but clinical and experimental data suggest that it involves altered central dopaminergic activity.

Adolescent↗

Stroke in users of low-dose oral contraceptives.

BACKGROUND: Previous studies have linked the use of oral contraceptive agents to an increased risk of stroke, but those studies have been limited to oral contraceptives containing more estrogen than is now generally used. METHODS: In a population-based, case-control study, we identified fatal and nonfatal strokes in female members of the California Kaiser Permanente Medical Care Program and who were 15 through 44 years of age. Matched controls were randomly selected from female members who had not had strokes. Information about the use of oral contraceptives (essentially limited to low-estrogen preparations) was obtained in interviews. RESULTS: A total of 408 confirmed strokes occurred in a total of 1.1 million women during 3.6 million woman-years of observation. The incidence of stroke was thus 11.3 per 100,000 woman-years. On the basis of data from 295 women with stroke who were interviewed and their controls, the odds ratio for ischemic stroke among current users of oral contraceptives, as compared with former users and women who had never used such drugs, was 1.18 (95 percent confidence interval, 0.54 to 2.59) after adjustment for other risk factors for stroke. The adjusted odds ratio for hemorrhagic stroke was 1.14 (95 percent confidence interval, 0.60 to 2.16). With respect to the risk of hemorrhagic stroke, there was a positive interaction between the current use of oral contraceptives and smoking (odds ratio for women with both these factors, 3.64; 95 percent confidence interval, 0.95 to 13.87). CONCLUSIONS: Stroke is rare among women of childbearing age. Low-estrogen oral-contraceptive preparations do not appear to increase the risk of stroke.

Adolescent↗

Effect of oral contraceptive agents on vitamin and mineral requirements.

Oral contraceptive agents alter the metabolism of some nutrients, which could affect nutritional requirements. The effects of oral contraceptives on pyridoxine, folacin, thiamin, riboflavin, vitamin A, ascorbic acid, zinc, and copper as determined by studies done in the last five years are reviewed. Evidence for actual nutritional deficiencies due to the use of oral contraceptives is still insufficient, and more research is needed. Supplements are advised only for those women in whom other factors, such as disease, impair nutritional adequacy.

Ascorbic Acid↗

The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.

BACKGROUND: Oral contraceptives can induce changes in lipid and carbohydrate metabolism similar to those associated with an increased risk of coronary heart disease, including increased serum triglyceride, low-density lipoprotein (LDL) cholesterol, and insulin levels and decreased high-density lipoprotein (HDL) cholesterol levels. In this study, we examined whether modification of the type or dose of progestin in oral-contraceptive preparations diminishes these changes. METHODS: We measured plasma lipoprotein levels and performed oral glucose-tolerance tests in a cross section of 1060 women who took one of nine types of oral contraceptives for at least three months and 418 women who took none. Seven of the contraceptive formulations contained various doses and types of progestin: levonorgestrel in low (150 micrograms), high (250 micrograms), and triphasic (50 to 125 micrograms) doses; norethindrone in low (500 micrograms), high (1000 micrograms), and triphasic (500 to 1000 micrograms) doses; and a new progestin, desogestrel, in one dose (150 micrograms). All seven contained 30 to 40 micrograms of ethinyl estradiol. Two additional formulations contained progestin alone. RESULTS: As compared with controls, women taking combination drugs did not have increased serum total cholesterol levels but did have increases of 13 to 75 percent in fasting triglyceride levels. Levels of LDL cholesterol were reduced by 14 percent in women taking the combination containing desogestrel and by 12 percent in those taking low-dose norethindrone. Levels of HDL cholesterol were lowered by 5 percent and 16 percent by the combinations containing low-dose and high-dose levonorgestrel, respectively; these decreases were due to reductions of 29 percent and 43 percent, respectively, in the levels of HDL subclass 2. The combination pill containing high-dose norethindrone did not affect HDL cholesterol levels, whereas that containing low-dose norethindrone increased HDL cholesterol levels by 10 percent. The desogestrel combination increased HDL cholesterol levels by 12 percent. Levels of apolipoproteins A-I, A-II, and B were generally increased by combination drugs. Depending on the dose and type of progestin, combination drugs were associated with plasma glucose levels on the glucose-tolerance test that were 43 to 61 percent higher than in controls, insulin responses 12 to 40 percent higher, and C-peptide responses 18 to 45 percent higher. Progestin-only formulations had only minor metabolic effects. CONCLUSIONS: The appropriate dose and type of progestin may reduce the adverse effects of oral contraceptives on many metabolic markers of risk for coronary heart disease. Progestin-only formulations or combinations containing desogestrel or low-dose norethindrone were associated wtih the most favorable profiles.

Adolescent↗

A comparative study of two estrogen dosages in combined oral contraceptives among Sudanese women.

A prospective study of two combined oral contraceptives was conducted in the Sudan. No pregnancies occurred. Overall incidence of side effects was low. Headache was most frequently reported. Elevations were observed for weight, systolic and diastolic blood pressures, and SGOT and SGPT values while a decrease was seen for hemoglobin levels. Menstrual irregularities were not a problem for the users. Total 6-month use discontinuation rates were low for both pill groups.

Contraceptives, Oral↗

Increased metabolic clearance of acetaminophen with oral contraceptive use.

The effect of chronic low-dose oral contraceptive steroid use on the pharmacokinetics of intravenous acetaminophen was determined. Eight women using low-dose (under 50 micrograms) estrogen oral contraceptive steroid for more than 3 months were matched for age and weight (mean age, 25.9 years; mean weight, 58.3 kg) with 8 female controls not using the steroid (mean age, 26.0 years; mean weight, 55.5 kg). No subject was taking other drugs. Oral contraceptive steroid subjects had a lower elimination half-life of acetaminophen (2.12 hours) than controls (2.71 hours) (P less than .005). Volume of distribution was similar for both groups (oral contraceptive group, 1.04 liters/kg; controls, 0.96 liters/kg; NS). Total metabolic clearance was significantly higher in oral contraceptive subjects (5.81 ml/min/kg, versus 4.12 ml/min/kg for controls; P less than .02). As volume of distribution and body weight are similar for both groups, the decrease in acetaminophen elimination half-life among contraceptive steroid users is the result of increased total metabolic clearance. Thus, low-dose estrogen oral contraceptive steroid may stimulate the metabolism of a conjugatively metabolized drug such as acetaminophen, in contrast to contraceptive steroid impairment of the clearance of some oxidatively metabolized drugs, with antipyrine being the prototype.

Acetaminophen↗

[Oral contraceptives and endometrial and ovarian carcinomas].

Combined oral contraceptives reduce the risk of endometrial and ovarian cancer by about 50%. The risk of both carcinomas decreases with an increasing duration of oral contraceptive use. The reduced risk lasts for 10-15 years after cessation. A significantly lower risk of developing an endometrial carcinoma can be observed for contraceptives with a high progestin and a low estrogen concentration. Due to the protective effect, the use of oral contraceptives is a useful means for primary prevention (chemoprevention) in women at high risk of endometrial and ovarian cancers.

Contraceptives, Oral, Combined↗

Oral contraceptive use and invasive cervical cancer.

The relationship between oral contraceptive use and the risk of invasive cervical cancer was investigated using data from a hospital-based case-control study conducted in the greater Milan area, Northern Italy. A total of 367 women under 60 years of age with a histologically confirmed diagnosis of invasive cervical cancer was compared with a group of 323 controls admitted for a spectrum of acute conditions, non-gynaecological, hormonal or neoplastic and apparently unrelated to oral contraceptive use. Cases had used oral contraceptives more frequently than controls, the age-adjusted relative risk (RR) being 1.53 (95% confidence interval 0.99-2.36). The risk increased with duration of use: compared with never users the age-adjusted RR was 1.48 for up to two years and 1.83 for more than two years (chi 2(1) = 5.28, p = 0.02). Allowing for major identified potential confounding factors, including sexual and reproductive habits, by means of multiple logistic regression, did not explain the association (multivariate RR 1.85 for ever use, 1.05 for up to two years and 2.47 for more than two years). When the interaction between oral contraceptive use and parity or sexual habits was analysed, the effects of various factors appeared independent: the point estimate for multiparous oral contraceptive users versus nulliparous never users was 8.01. There was no consistent influence on risk of invasive cervical cancer of age at first use, whereas the RRs were slightly greater for women who had first used oral contraceptives less than ten years before or had last used them less than five years before diagnosis: these findings, however, were far from significant.

Adult↗

Selection of steroid combinations for oral contraceptives of maximum benefit.

Low-dose oral contraceptives differ in the specific progestin component. Our review of available animal and human data revealed differences between the progestins as to their potencies for estrogenic, anti-estrogenic, androgenic and progesterone effects. Ideally, oral contraceptive formulations should have the minimal effective dose, sufficient to prevent pregnancy but with the fewest metabolic changes. The risk of cardiovascular disease may be predicted by changes in the composition and amount of circulating lipoproteins. Progestins with significant androgenic potency can lower high-density lipoprotein2; that is a possible adverse effect. Randomized, blind, comparative trials of the new multiphasic preparations are needed to determine which ones truly cause the fewest metabolic changes that might be of clinical significance.

Animals↗

A prospective study of pregravid oral contraceptive use and risk of hypertensive disorders of pregnancy.

Oral contraceptive use is associated with hypertension, dyslipidemias, and insulin resistance, all of which also characterize hypertensive disorders of pregnancy. In this prospective cohort study, the association of oral contraceptive use before pregnancy and the risk of gestational hypertension and preeclampsia was assessed. Between 1991 and 1995, 3973 nulliparous women who reported their first pregnancy lasting > or = 6 months were studied. Pregravid exposures were collected by biennial mailed questionnaires, and cases were confirmed by medical record review. Recent oral contraceptive use was defined as use within 2 years of pregnancy. Proportional hazards analysis was used to adjust for potential confounding variables. During the 4 years of follow-up, 133 (3.3%) women with gestational hypertension and 62 (1.6%) with preeclampsia were identified. Twenty-five percent of women who did not develop these disorders were recent users of oral contraceptives, compared with 19% (p = 0.11) of women who developed gestational hypertension and 30% (p = 0.38) who developed preeclampsia. Mean duration of prior oral contraceptive use was similar for cases and noncases. Compared with never and past users, the multivariate relative risk among recent users for developing gestational hypertension was 0.7 (95% confidence interval (CI), 0.4-1.0) and for preeclampsia was 1.3 (95% CI, 0.8-2.4). Among recent users who had used oral contraceptives for > or = 8 years, the relative risk for gestational hypertension was 0.6 (95% CI, 0.3-1.2) and for preeclampsia was 2.1 (95% CI, 1.1-4.2). When the analysis was restricted to women who had never smoked, the risk for gestational hypertension was 0.2 (95% CI, 0.1-0.9) and for preeclampsia was 4.1 (95% CI, 1.9-8.7). Thus, recent use of oral contraceptives was associated with a reduced risk for developing gestational hypertension. In contrast, there was a suggestion that recent use was associated with an increased risk of developing preeclampsia, but only among women who had used these agents for > or = 8 years.

Adult↗

Oral contraceptives and thromboembolism: a reassessment.

The relationship between oral contraceptive usage and thromboembolism is controversial. Since thromboembolism is often undiagnosed, both clinically and at routine autopsy, most epidemiologic analyses rest or a very uncertain factual base. There are increases in blood coagulation factors in oral contraceptive users similar to, but less than, those seen in pregnancy, which is not associated with increased thromboembolism. Hematologists emphasize that these changes do not define a "hypercoagulable" state, and they do not define or predict the occurrence of thrombosis. Intrinsic vascular wall changes, unrelated to drug use, may play a role in sporadic cases of thromboembolism. When the incidence of thromboembolism in very large Phase III trials of conventional oral contraceptives is compared to that in other populations (patients admitted to the hospital, women who visit a physician, pregnant women, or users of nonestrogenic oral contraceptives), no difference is seen. Epidemiologic studies by the "case-control" ("trohoc") method consistently show an increase "relative risk" associated with oral contraceptive use in subjects with "idiopathic" thromboembolism but no increased risk in thromboembolism patients as a whole or in those with predisposing factors. This retrospective epidemiologic technique, its particular applications, and the inferences drawn are open to serious criticism, as are studies claiming a relationship between estrogen dose and thromboembolism incidence. An Australian prospective survey found no increased risk among users, and a large British study which initially reported an increased risk is currently undergoing recalculation. The only controlled clinical experiment (with random assignment of subjects to vaginal versus high-estrogen contraceptives) showed no increased incidence in the drug-treated group. Statistical associations derived from "trohoc" studies do not establish causal relationships; moreover, their risk estimates are in conflict with the findings of large Phase III clinical surveys including subjects using estrogen-free contraceptives, with at least one prospective clinical survey, and with a randomized, controlled clinical trial. The data relating estrogen dosage to thromboembolism incidence are ambiguous, at best. Thus, the claim of a causal relationship between oral contraceptive steroids and thromboembolism does not appear to be firmly founded, and the belief that predisposing factors increase the risk to contraceptive users is equally insubstantial.

Adolescent↗

Yasmin--a new oral contraceptive, a new progestogen: the reasons why.

There are over 60 million women using oral contraceptives worldwide, yet there are wide differences between different countries in the use of oral contraceptives and, in particular, in discontinuation rates. Large differences in rates of sterilization and of teenage pregnancy also highlight the fact that there are considerable geographical differences in oral contraceptive use. There are probably many reasons for these differences, including lack of information about the non-contraceptive benefits of oral contraceptives, differences in national health-care policies and systems, women's fears about side-effects and possible side-effects, and social, cultural and religious differences. In order to provide better choices of oral contraceptives, there is a need to consider new oral contraceptives, such as Yasmin (Schering AG, Berlin, Germany), which is formulated with ethinylestradiol and drospirenone, a progestogen which is pharmacologically very similar to progesterone. Unlike other progestogens, drospirenone is associated with weight stability or slight weight loss due to less water retention, one of the factors which is known to be of great importance in supporting compliance with oral contraceptives. Drospirenone also shares with some other progestogens the capacity to improve acne and seborrhea in hyperandrogenic women. Taken together, these properties make it likely that the combination of ethinylestradiol with drospirenone will contribute to improving oral contraceptive compliance, thereby maximizing the overall benefits of oral contraception.

Androstenes↗

Self-reported oral contraceptive use and peripheral joint laxity.

STUDY DESIGN: A masked, single-factor, posttest-only control group design. OBJECTIVE: To explore the relationship between reported oral contraceptive use and peripheral joint laxity. BACKGROUND: Studies have found an association between increased ligamentous laxity and changes in serum levels of hormones such as estrogen, progesterone, and relaxin. Two of these hormones, estrogen and progesterone, are present in most oral contraceptives. Oral contraceptive users, therefore, provide a population for studying the effects of these hormones on the degree of ligamentous laxity. METHODS AND MEASURES: Fifty-five women between the ages of 20 and 25 years participated in this study. Thirty users of oral contraceptives were a test group and 25 nonusers of oral contraceptives were controls. The KT-1000 Arthrometer was used to measure passive anterior translation of the tibia in relation to the femur in both knees. Passive abduction and adduction of the proximal interphalangeal (PIP) joint of the second digit of the nondominant hand and distal interphalangeal (DIP) joint hyperextension of the fifth digit of the nondominant hand were measured using a goniometer. A subjective measurement of passive second PIP joint motion was also assessed and a value of minimum, moderate, or maximum laxity was assigned. Independent sample t tests were performed to compare the measurements of the oral contraceptive user and nonuser groups for each joint. A chi-square test compared the subjective PIP joint data between the 2 groups. RESULTS: No significant differences in laxity measurements at the knee or hand were found between the 2 groups. Average knee laxity varied between 5.7-7.9 mm of anterior displacement for both groups. Average PIP abduction and adduction varied between 6.5-6.7 degrees for both groups and DIP hyperextension was 28.6-29.9 degrees. CONCLUSIONS: Results of this study indicate that self-reported oral contraceptive use was not associated with peripheral joint laxity.

Adult↗

Oral contraception and the recognition of endometritis.

OBJECTIVE: Oral contraceptive use has been associated with a lower risk of symptomatic pelvic inflammatory disease but a higher risk of chlamydial cervicitis. To explain these seemingly contradictory findings, we asked whether oral contraceptive use was more common among women with unrecognized endometritis than among women with recognized endometritis. STUDY DESIGN: A multicenter case-control study was performed. Women without signs of pelvic inflammatory disease were ascertained through contact tracing of partners with sexually transmitted diseases or through presentation with cervicitis. Women with symptomatic pelvic inflammatory disease met a set of standard clinical criteria. We compared the 43 cases without signs of pelvic inflammatory disease but with endometritis ("unrecognized endometritis") with the 111 controls with recognized pelvic inflammatory disease and endometritis ("recognized endometritis"). RESULTS: Women with unrecognized endometritis were 4.3 times (95% confidence interval 1.6 to 11.7) more likely than women with recognized endometritis to use oral contraceptives. CONCLUSION: Future studies need to fully characterize the risks and benefits of oral contraceptives in relation to sexually transmitted diseases.

Adult↗

A prospective study of fertility and outcome of pregnancy after discontinuation of oral contraception in relation to elective orthopedic surgery.

OBJECTIVE: To evaluate the risk of unwanted pregnancies, their outcome and the rate of resuming contraception after discontinuation of oral contraception (OC) prior to elective surgery. DESIGN: A six months prospective follow-up study. SETTING: Orthopedic unit, operating on a total of 897 women during a period of 24 months. SUBJECTS: Seventy-eight healthy women in whom OC was stopped prior to elective orthopedic surgery. OUTCOME: Pregnancy rate, pregnancy outcome and reinstitution rate of OC. RESULTS: Complete outcome data are available for 73 (93.5%) of 78 women who were asked to participate in the study. Five pregnancies were reported, giving a cumulated six month pregnancy rate of 6.8%. Three pregnancies were completed to term, one was ectopic and one terminated by induced abortion. Within six months after the operation the cumulative user rate of oral contraceptives was 74.2%. None of the women were readmitted to hospitals for severe illness during the study period. CONCLUSIONS: The women resumed oral contraceptives relatively soon after their first post-operative menstrual cycle. This may explain why the pregnancy rate during the first six postoperative months appears low.

Abortion, Induced↗

Reduction of the risk of rheumatoid arthritis among women who take oral contraceptives.

Discrepant results among investigations of the association between oral contraceptive use and rheumatoid arthritis (RA) have been ascribed to shortcomings in the study methods. In the present study, we obtained detailed information on oral contraceptive use in 135 young women with confirmed definite or classic RA of recent onset and in 378 controls with soft tissue rheumatism or osteoarthritis. All patients had at least 2 years of followup to confirm the consistency of the diagnosis. Oral contraceptive use at any time before disease onset was reported by 70% of the RA patients and 85% of the controls; the latter figure corresponded to general population data for The Netherlands. This yielded a relative risk for RA of 0.39 among those who had ever used oral contraceptives and 0.58 for those using oral contraceptives at the time of symptom onset. The preventive effect of oral contraceptive use on the risk of RA was found to be independent of the dose, duration of use, or presence of HLA-DR4. The strongest protection was seen in women with a family history of RA and in women ages 31-40 at symptom onset. The conflicting results in the literature are discussed, and a possible biologic mechanism for this phenomenon is suggested.

Adult↗

Dietary folate intake and concentration of folate in serum and erythrocytes in women using oral contraceptives.

Conflicting reports regarding the possible effect of oral contraceptives agents (OCA's) on folate status prompted us to evaluate the relationship between dietary folate intake and the concentration of folate in serum and erythrocytes among users and nonsuers of OCA's during two consecutive menstrual cycles. Twenty-two women (ages 19 to 28) had been on combination type OCA's for 4 months or more and a control group of 18 women (ages 18 to 29) had not used OCA's for at least 6 months prior to this study. The serum folate levels were lower in the OCA users than in the controls and the difference was statistically significant on day 5 of the menstrual cycle (P less t-an 0.05) but not on day 20. However, the differences in the erythrocyte folate levels and dietary folate intakes were not statistically significant between the two groups of subjects. There was a consistently higher degree of correlation between serum folate and folate intake among the control women than among the OCA users. Hematological parameters such as hemoglobin, hematocrit, mean corpuscular volume, mean corpusclar hemoglobin, mean corpuscular hemoglobin concentration and red cell count were similar in the two groups. It is concluded that the use of OCA's produces significantly lower serum folate levels during the first week of the menstrual cycle in spite of adequate folate intake.

Adult↗