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Oral contraceptives and breast cancer: latest findings in a large cohort study.

During the interval 1968-74, 17,032 women aged 25-39 years were recruited to the Oxford-Family Planning Association contraceptive study, more than half of whom were using oral contraceptives. These women have been followed up over the years and breast cancer has been diagnosed in 189 of them. We have analysed the available data in two ways. First, we have calculated standardised breast cancer incidence rates in non-users and users of oral contraceptives according to total duration of use, interval since first use, interval since last use, duration of use before first term pregnancy and duration of use before age 25. Secondly, we have conducted case-control within cohort analyses to examine the possible effects of different types of pill and to search for evidence of a latent effect of oral contraceptive use before first term pregnancy on breast cancer risk. We have found no evidence of any adverse effect of oral contraceptive use on the risk of breast cancer in this study. There was, however, little exposure to the pill before first term pregnancy among the participants and virtually no such exposure at a very young age (i.e. below 20 years). Accordingly, the results of this study strengthen the evidence that oral contraceptive use by mature women does not increase breast cancer risk, but add little to the uncertainty about the effects of early use.

Adult↗

Effects of oral contraceptives on the gallbladder bile of normal women.

In view of the reported association between use of oral contraceptives and gallbladder disease, the effects of contraceptive steroids on the lipid composition of gallbladder bile were studied in 22 healthy women. Each subject was studied during routine use of oral contraceptives and also during normal menstrual cycles on no medication. Gallbladder bile was significantly more saturated with cholesterol during contraceptive therapy than during normal menstrual cycling (125 versus 92 per cent, P less than 0.001). Chenodeoxycholic acid accounted for a significantly smaller proportion (35 versus 42 per cent P less than 0.001) and cholic acid a significantly greater proportion (50 versus 41 per cent (P less than 0.001) of total bile acids during contraceptive steroid therapy. These findings show that exogenous sex steroids in doses and formulations routinely prescribed induce important alterations in the composition of human gallbladder bile, and suggest a biochemical basis for the increase in gallbladder disease observed among women using oral contraceptives.

Adult↗

High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives.

BACKGROUND: Idiopathic cerebral-vein thrombosis can cause serious neurologic disability. We evaluated risk factors for this disorder, including genetic risk factors (mutations in the genes encoding factor V and prothrombin) and nongenetic risk factors (such as the use of oral contraceptive agents). We compared the prevalence of these risk factors in 40 patients with cerebral-vein thrombosis, 80 patients with deep-vein thrombosis of the lower extremities, and 120 healthy controls. The G1691A mutation in the factor V gene and the G20210A prothrombin-gene mutation, which are established genetic risk factors for venous thrombosis, were studied. We also assessed the use of oral contraceptives and other risk factors for thrombosis. RESULTS: The prevalence of the prothrombin-gene mutation was higher in patients with cerebral-vein thrombosis (20 percent) than in healthy controls (3 percent; odds ratio, 10.2; 95 percent confidence interval, 2.3 to 31.0) and was similar to that in patients with deep-vein thrombosis (18 percent). Similar results were obtained for the mutation in the factor V gene. The use of oral contraceptives was more frequent among women with cerebral-vein thrombosis (96 percent) than among controls (32 percent; odds ratio, 22.1; 95 percent confidence interval, 5.9 to 84.2) and among those with deep-vein thrombosis (61 percent; odds ratio, 4.4; 95 percent confidence interval, 1.1 to 17.8). For women who were taking oral contraceptives and who also had the prothrombin-gene mutation (seven patients with cerebral-vein thrombosis but only one control), the odds ratio for cerebral-vein thrombosis rose to 149.3 (95 percent confidence interval, 31.0 to 711.0). CONCLUSIONS: Mutations in the prothrombin gene and the factor V gene are associated with cerebral-vein thrombosis. The use of oral contraceptives is also strongly and independently associated with the disorder. The presence of both the prothrombin-gene mutation and oral-contraceptive use raises the risk of cerebral-vein thrombosis further.

Adolescent↗

The effect of oral contraceptive agents on the basal metabolic rate of young women.

The use of oral contraceptive agents by women may be a factor that contributes to the observed inter-individual variability in the BMR. We, therefore, measured the BMR, body build and composition in two groups of young women and also assessed their self-reported level of physical activity. One group had been using oral contraceptive agents for a period of 6 months or more (OCA, n 24), while the other group had never used oral contraceptives (NOCA, n 22). There were no significant differences in age, body build or composition. The absolute BMR in the groups were not significantly different when compared using an unpaired t test (OCA: 5841 (SD 471) v. NOCA: 5633 (SD 615) kJ/d). However, using an analysis of covariance, with either body weight or a combination of fat and fat free mass as covariates, the OCA group had a BMR almost 5% higher than that of the NOCA group (OCA: 5871 v. NOCA: 5601 kJ/d; P = 0.002). When those subjects with high self-reported levels of physical activity were excluded, the difference in BMR between the two groups persisted (P = 0.001). An ANOVA of oral contraceptives use and phase of menstrual cycle showed significant differences in BMR with use of oral contraceptives (P = 0.004) but no difference in BMR between phases of the menstrual cycle. In conclusion, the use of oral contraceptive agents deserves consideration when conducting and analysing data from studies on energy metabolism in young women, as it results in a significantly higher BMR.

Adult↗

Contraceptive practices before conception and after the birth of a child with a chronic health problem.

Sexual and marital relations as well as family functioning may be altered by the birth of a child with a chronic health problem. After the birth of a child with a health problem, mothers have varied responses from an urgent desire to have another baby to a firm desire to avoid pregnancy. Mothers of healthy infants and mothers of infants who had been placed on apnea monitors for at least 5 months were surveyed on their contraceptive practices, family functioning, their marital satisfaction and sexual satisfaction, as well as their desire to have or not have another child. Surveys were conducted at 6 months and 12 months after delivery. The type of contraception used varied significantly between the two groups of mothers. There was an increase in the use of oral contraception after birth for the women whose infants were on apnea monitors. Frequency in the use of contraception varied between the two groups, with the mothers of healthy infants reporting more consistent use prior to the pregnancy, which was also more frequently planned than in the apnea group. Correlation matrices demonstrated a significant relationship between type of contraception and marital satisfaction, employment, and spousal support. The findings reinforce the need for health professionals to assist families in identifying how the birth of a child with chronic health problems has affected the family. Contraception counseling as well as marital counseling may be needed for some families.

Apnea↗

Barrier versus oral contraceptive use: a study of female college students.

Although they provide birth control and are easier to use, oral contraceptives (OCPs) are not the preferred approach to preventing sexually transmitted disease (STD). Do the knowledge, attitudes, and experiences of oral contraceptive users place them at greater risk for STDs than those who employ barrier methods? This study examined differences between sexually active female college students (ie, those who reported ever having had vaginal intercourse) who used OCPs and those who employed barrier methods of contraception at the time of their most recent intercourse. The authors analyzed HIV- and other STD-related knowledge, attitudes, and behaviors from three consecutive annual health surveys of young women about to begin their first year of college. Findings showed barrier and OCP users to be comparable in knowledge about the effectiveness of various contraceptive methods in protecting them against STDs, perceived personal susceptibility to HIV, and experiences with alcohol before sexual intercourse. Oral contraceptive users, compared with those in the group who used barrier methods, reported a greater number of recent partners (p less than .03) and greater perceived vulnerability to STDs (p less than .03). Student healthcare providers must develop creative educational strategies to encourage simultaneous use of both oral contraceptives and barrier methods to protect students against STDs and pregnancy.

Adolescent↗

Vitamin B6 status of Nigerian women using various methods of contraception.

The vitamin B6 status of Nigerian women, and the effects of three contraceptive methods--intrauterine contraceptive device, injectable progestogen, and combination estrogen-progestogen oral contraceptive pills--on the vitamin B6 status of these women were assessed by measuring the erythrocyte alanine aminotransferase (Ala-AT) activity both with and without in vitro stimulation by pyridoxal-5'-phosphate. The unstimulated Ala-AT activity and the Ala-AT index (ratio of pyridoxal-5'-phosphate-stimulated:unstimulated activity) were used as indications of vitamin B6 status. The criterion for vitamin B6 deficiency was an Ala-AT index greater than 1.25. Of the 238 women in the total sample, 11% were judged to be deficient. There were no significant differences in the mean Ala-AT activity, mean Ala-AT index or rate of deficiency foun in the control and three contraceptive groups. The absence of an effect of oral contraceptives on vitamin B6 status is in contrast with other cross-sectional studies, but in agreement with controlled longitudinal studies. The packed cell volume and reticulocyte count were also measured and were significantly affected by contraceptive steroids, but these effects are not thought to be of clinical importance.

Adult↗

Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer.

Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent. This inconsistency may be due in part to the biological heterogeneity of colorectal tumors. A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma. Fifty per cent (32/64) of colorectal tumors displayed nuclear over-expression of p53 protein. Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02). In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10). These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer.

Aged↗

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↗

Validity of contraceptive histories in a rural community in Kenya.

To determine the validity of self-reported contraceptive histories obtained from rural Kenyan women, we interviewed 122 women participants in a long-term study during which their contraceptive use had been recorded regularly at clinics. Interview information was compared with each woman's clinic record. In all 71 women (58%) reported ever use of oral contraceptives, while 76 (62%) of the clinic records documented ever use. The agreement between the records and interview was reasonable (Kappa = 0.54, P < 0.001). The sensitivity of self-report of use compared to clinic records was 79%, specificity was 76%, positive and negative predictive values were 85% and 69% respectively. Ever use of injectable contraceptives (Depo-Provera) was reported by 78 (63%) women while the records showed use by 80 (65%) women (Kappa = 0.87, P < 0.001). The sensitivity, specificity, positive and negative predictive values were 94%, 93%, 96%, and 89% respectively. For the intrauterine contraceptive device, ever use was reported by 18 (14.8%) women while the records showed 19 (15.6%) (Kappa = 0.90, P < 0.001). The associated sensitivity, specificity, positive and negative predictive values were 90%, 99%, 94% and 98% respectively. The validity of reported duration of use of each method showed a similar pattern to that of the history of ever use. The Spearman's rank correlations for the duration of use calculated from interview compared with the clinic records were for oral contraceptives r = 0.68 (P < 0.001), injectables r = 0.81 (P < 0.001) and intrauterine devices r = 0.82 (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epidemiological models and related simulation results for understanding of contraceptive adoption in India.

BACKGROUND: For the first time, models using multilevel analysis of Indian data and related simulation results are reported. They take hierarchical structure into account and incorporate variables from all levels to get correct analysis and proper interpretation of data on current contraceptive use (including sterilization and modern methods). METHODS: The data from an Indian State, Uttar Pradesh (UP), collected by the National Family Health Survey (NFHS) conducted during 10 October 1992 to 22 February 1993 was used. For model I, 7851 currently married women who were neither pregnant nor had continuing post-partum amenorrhoea (PPA) were considered. For model II, these women with at least one child (n = 6748) were used. Two-level logistic regression analysis was carried out for which women's level (level 1) and PSU (Primary Sampling Unit) level (level 2) variables were considered. The results were considered significant at the 5% level of significance. Simulation analysis using each model was also carried out. RESULTS: Model I reveals that those more likely to adopt contraception were women exposed to a TV message (odds ratio [OR] = 1.3; 95% CI: 1.1-1.6); whose houses were pucca (bricks and mortar) (OR = 1.3; 95% CI: 1.1-1.5); who were educated to high school level and above (OR = 2.9; 95% CI: 2.2-3.7); whose husbands were literate with schooling of > or =11 years (OR = 1.7; 95% CI: 1.4-2.1); and who had > or =2 living sons (OR = 2.2; 95% CI: 1.1-4.4). Muslim and other religious women were less likely than Hindu women to adopt contraception (OR = 0.5; 95% CI: 0.4-0.6). Also, the PSU level availability of all weather road was positively associated with contraceptive adoption (OR = 1.4; 95% CI: 1.1-1.7). The PSU level variance, which is the unexplained PSU level variation after controlling for the considered characteristics, was significantly higher. The simulation results revealed that public health education (a TV message) was found to be more effective among less educated women. The PSU level availability of all weather road was as effective as public health education. Similar results were evident from the analysis of second data set (model II) with the noticeable finding that those whose last child is surviving are most likely to adopt contraception (OR = 8.82; 95% CI: 1.01-77.38). CONCLUSIONS: These results reveal that the survival status of the last child has a marked effect on the adoption of contraception in UP. They further support the idea that public health education (a TV message) is more effective among less educated women. Also, the PSU level presence of all weather road is equally effective. Consideration of higher level variables provides not only more accurate results but also important public health clues to help the policy planners.

Adolescent↗

Agreement rates between oral contraceptive users and prescribers in relation to drug use histories.

A comparison between prescriber records and patient-reported oral contraceptive histories obtained during a case-control study of thromboembolism and oral contraceptive use served as the basis for evaluating the extent of agreement between these two sources of information. Agreement between oral contraceptive user and prescriber was highest on the name of the most recently-used product (89% agreement), and dropped to 62.5% on the name of the product taken before the more recent one. For total duration of oral contraceptive use (to within one month of hospital admission), agreement (defined as differences not exceeding one month) was 36%, while 39% showed the users reporting longer duration of use, and 25% showed users reporting shorter duration. Cases showed a higher rate of agreement with prescriber records than the controls on both the name of the product and the total duration of use. Disagreement from prescriber records in the direction of reporting longer duration of use was 45% for the controls compared to 27% for the cases. These results indicate that while user information in connection with the most recently used oral contraceptive can be acceptable in studies employing the case-control research strategy, user reports about previous oral contraceptive use may be less useful.

Adolescent↗

Increased risk of inflammatory bowel disease associated with oral contraceptive use.

Research on inflammatory bowel disease risk among oral contraceptive users has reached conflicting conclusions. This population-based case-control study evaluated the effects of oral contraceptive use on ulcerative colitis and Crohn's disease risk. Cases were women enrollees, aged 15-68 years, of Group Health Cooperative of Puget Sound (a prepaid health plan based in western Washington State) who had ulcerative colitis (n = 211) or Crohn's disease (n = 91). Age-matched controls were randomly selected from the health plan enrollment file. An in-person interview obtained information about lifetime contraceptive use. Conditional logistic regression analysis was used to estimate relative risks and 95% confidence intervals for disease. Women who reported oral contraceptive use within 6 months before disease onset were at increased risk for both diseases compared with never users (relative risk (RR) of ulcerative colitis = 2.0, 95% confidence interval (CI) 1.2-3.3; RR of Crohn's disease = 2.6, 95% CI 1.2-5.5). Women who had used oral contraceptives for more than 6 years had the highest risk of Crohn's disease (RR = 5.1, 95% CI 1.8-14.3). In contrast, increasing duration of use was not associated with increased risk of ulcerative colitis. Adjustment for race, smoking, income, or pregnancy history did not substantially alter these results. Higher ulcerative colitis risk tended to occur among users of high estrogen dose oral contraceptives, while Crohn's disease risk was similar regardless of estrogen potency.

Adolescent↗

Erroneous clinical diagnosis of leg vein thrombosis in women on oral contraceptives.

Most studies demonstrating an increased risk of venous thromboembolism in women on oral contraceptives are based on clinical manifestations of the disease. Because of the fallibility of the clinical diagnosis of suspected leg vein thrombosis, Doppler ultrasonic evaluation (with a 93% accuracy compared to venography) was performed for clinical manifestations in deep vein thrombosis in 54 women taking birth control pills and 75 women of similar age who were not on contraceptives. The clinical diagnosis was confirmed by Doppler in only 16.7% of the women taking contraceptives and 30.7% of women not taking contraceptives (P = 0.052). This study suggests that the clinical diagnosis of leg vein thrombosis is frequently erroneous, particularly in women taking oral contraceptives. Future investigations reporting venous thromboembolism associated with oral contraceptives should be based on diagnoses validated by accurate objective techniques.

Adolescent↗

Effects of subjects' sex, and intake of tobacco, alcohol and oral contraceptives on plasma phenytoin levels.

1. Steady state plasma phenytoin levels in 210 epileptic patients were studied by computerized analysis of covariance to determine whether the subject's sex, alcohol intake, tobacco smoking or use of oral contraceptives influenced the relation between plasma drug level and drug dose. 2. Sex, tobacco smoking and alcohol usage had no statistically significant effect. There was a trend towards higher phenytoin levels relative to drug dose in oral contraceptive users. 3. This finding prompted an additional study of plasma phenytoin levels in 40 oral contraceptive users and 135 aged matched non-users. Analysis of covariance again showed higher plasma phenytoin levels relative to drug dose in users of oral contraceptives (P = 0.061). 4. This finding raised the possibility that the relation between plasma phenytoin level and drug dose differed between males and females who did not use oral contraceptives. However, when the relation between plasma phenytoin levels and drug dose was compared in 159 females who did not use oral contraceptives and 101 males (both groups aged 15 to 70 years) no statistically significant difference was found.

Adolescent↗

Trends in male contraception.

Methods that are available for male contraception, namely coitus interruptus, condoms, and vasectomy, have been used since the 19th century. With the exceptions of a few improvements of these methods, no major progress has been made with respect to introducing new male contraceptives since then. It is extremely urgent to develop new, safe, effective, and reversible male contraceptive methods. Among all male contraceptive methods that are being investigated, the hormonal approach is the closest to clinical application. Hormonal contraception provides pregnancy protection by means of spermatogenic suppression. Androgen-progestin regimens currently represent the best available hormonal combination for induction of a profound suppression of spermatogenesis. Further development of new steroids is mandatory for increasing the choices of available contraceptive formulations and to optimize long-term safety of these regimens.

Androgens↗

Oral contraceptive use among female elite athletes and age-matched controls and its relation to low back pain.

BACKGROUND: Exogenous and endogenous female sex steroids may influence the risk of low back pain. The fact that back pain is a very common symptom during pregnancy supports this theory. Back pain is also more common among female than male athletes. Oral contraceptives have been suggested to increase the risk of low back pain. OBJECTIVE: To evaluate whether the prevalence of low back pain is higher among oral contraceptive users than non-users and if it differs between women taking part in different sports. METHODS: A questionnaire was sent to female elite athletes in volleyball (n = 205), basketball (n = 150), and soccer (n = 361) as well as to age-matched controls (n = 113). The questionnaire comprised questions about age, constitution, occupation, parity and use of contraceptive method as well as previous and current back pain and possible consequences of the back problems. RESULTS: The response rate was 85%. Between 42% and 52% of the women in the different groups used oral contraceptives. The groups were similar in most background variables, except that the volleyball and basketball players were taller. The prevalence of current low back pain was between 21% and 34% in the different athlete groups with an average of 30%, whereas only 18% of the controls suffered from low back pain (p < 0.01). The prevalence of low back pain within each group, athletes as well as controls, was similar in women who used, and did not use oral contraceptives. CONCLUSIONS: This study does not support the theory that low back pain is affected by the use of oral contraceptives. Instead, constitutional factors and mechanical stress during intense physical activity is probably more important.

Adult↗

Abnormal uterine bleeding associated with hormonal contraception.

Millions of women in the United States use some type of hormonal contraception: combination oral contraceptive pills (OCPs), progestin-only pills, medroxyprogesterone acetate injections, or subdermal levonorgestrel implants. Abnormal uterine bleeding is a common but rarely dangerous side effect of hormonal contraception. It is, however, a major cause for the discontinuation of hormonal contraception and the resultant occurrence of unplanned pregnancy. The evaluation of abnormal uterine bleeding in women who are using hormonal contraception includes an assessment of compliance, a thorough history and complete physical examination to exclude organic causes of bleeding, and a targeted laboratory evaluation. Pregnancy and the misuse of OCPs are frequent causes of abnormal uterine bleeding. Bleeding is common during the first three months of OCP use; counseling and reassurance are adequate during this time period. If bleeding persists beyond three months, it can be treated with supplemental estrogen and/or a nonsteroidal anti-inflammatory drug (NSAID). Other options are to change to an OCP with a higher estrogen content or to a different formulation (i.e., a low-dose OCP containing a different progestin). Management strategies for women with abnormal uterine bleeding who are using progestin-only contraceptive methods include counseling and reassurance, as well as the administration of supplemental estrogen and/or an NSAID during bleeding episodes.

Contraceptive Agents, Female↗