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PubMed2001

Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria.

BACKGROUND: Controversy exists regarding the adverse and beneficial effects of oral contraceptive use and hormone replacement therapy. Microalbuminuria is associated with increased risk of renal and cardiovascular disease. OBJECTIVE: To examine the association between oral contraceptive use or hormone replacement therapy and microalbuminuria. METHODS: We performed a case-control study of the baseline data and historical pharmacy data of 4301 female subjects of the Prevention of Renal and Vascular End Stage Disease study cohort, aged 28 to 75 years, excluding women who were pregnant or had type 1 diabetes mellitus. The main outcome measure was microalbuminuria, defined as a urinary albumin excretion of 30 to 300 mg per 24 hours (recorded as the mean of two 24-hour urine collections). RESULTS: After adjusting for age, hypertension, diabetes, obesity, hyperlipidemia, and smoking, the odds ratio (OR) for having microalbuminuria was 1.90 (95% confidence interval [CI], 1.23-2.93) for premenopausal oral contraceptive users and 2.05 (95% CI, 1.12-3.77) for postmenopausal hormone replacement therapy users. The point estimate increased in a dose-dependent fashion, albeit insignificantly, according to the estrogen content of the oral contraceptives (<30 microg ethinyl estradiol: OR, 1.11; 95% CI, 0.14-8.56; 30 to <50 microg: OR, 1.83; 95% CI, 1.17-2.87; and 50 microg: OR, 2.72; 95% CI, 0.81-9.08). The OR was greater in oral contraceptives with a second-generation (OR, 2.04; 95% CI, 1.28-3.25) vs a third-generation progestin (OR, 1.39; 95% CI, 0.63-3.06). The OR increased with the duration of hormone replacement therapy (< or =5 years, OR, 1.28; 95% CI, 0.37-4.50; >5 years, OR, 2.56; 95% CI, 1.32-4.97). CONCLUSION: Regular and long-term oral contraceptive use and hormone replacement therapy are associated with an increased risk for microalbuminuria and cardiovascular disease.

Adult↗
PubMed2004

Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review.

Venous thromboembolic events (VTEs) represent a serious complication related to hormonal contraception and hormone replacement therapy (HRT). Evidence on hormonal contraceptive- and HRT-related VTEs is derived almost exclusively from observational studies and points to a 2- to 6-fold increased relative risk of VTEs with either therapy. Oral contraceptive pills that contain third-generation progestins (desogestrel or gestodene) seem to be associated with greater VTE risk than those that contain levonorgestrel. Oral contraceptive pill use and HRT are associated with exponentially higher VTE relative risks when used by women who carry an inherited hypercoagulable state. The indication of a lower or a lack of VTE risk associated with the use of progestin-only contraceptives and with transdermal HRT suggests that these therapies may be safer than combination oral contraceptive pills and oral HRT for women in whom oral estrogen therapy is considered contraindicated. Data that support such safety advantages are limited and should be interpreted with caution.

Contraceptives, Oral, Hormonal↗
PubMed1977

Cancer risk as related to use of oral contraceptives during fertile years.

A case-control study of 452 breast cancer patients, aged less than 50 years, and 872 age-, race-, and religion-matched control patients generated relative risk estimates of breast cancer associated with oral contraceptive practices. The relative risk of breast cancer from ever-use of oral contraceptives was 1.1, not significant. Relative risks did not differ by age, interval since first use, interval since last use, or time periods in which steroid compounds differed in composition and potency. However, the relative risks of breast cancer from current use, from 2 to 4 years of ever-use, from 6 or more years of use by women with prior benign breast disease, and from use before first childbirth were increased significantly. The findings suggest the malignant process may be quickened if transformed cells are present during oral contraceptive use. Yet, the findings neither indicate that oral contraception induces breast cancer nor do they exonerate female steroid hormones. The findings do encourage continued surveillance of steroid contraception for cancer induction or promotion. In addition to duration of oral contraceptive use and other measures of dose response, future observations should pay especial attention to use by women before first childbirth and by women with already established benign breast disease.

Adolescent↗
PubMed1990

Oral contraceptives and breast cancer. Review and meta-analysis.

To evaluate the relation between use of oral contraceptives and the incidence of breast cancer, the authors reviewed the epidemiologic literature and used quantitative methods to summarize the data. Study results for any use of oral contraceptives were pooled using a model that accounted for both interstudy and intrastudy variability. The authors also explored interstudy variability and modeled a duration-effect relation between oral contraceptive use and breast cancer. Case-control and follow-up studies were considered separately. Overall, the authors observed no increase in the risk of breast cancer for women who had ever used oral contraceptives, even after a long duration of use. These results were consistent across study design. However, data combined from case-control studies revealed a statistically significant positive trend (P = 0.001) in the risk of premenopausal breast cancer for women exposed to oral contraceptives for longer duration. This risk was predominant among women who used oral contraceptives for at least 4 years before their first term pregnancy (relative risk = 1.72; 95% confidence interval = 1.36 to 2.19). Additional study is required to determine whether this finding in a subgroup of exposed women is confirmed and whether the risk remains increased with advancing age.

Adult↗
PubMed1980

Influence of environmental chemicals on drug therapy in humans: studies with contraceptive steroids.

The effects have been studied of various environmental factors on the variability in response to oral contraceptive steroid therapy in women. Ten- to thirty-fold variations in plasma concentrations of norethisterone, L-norgestrel and ethinyloestradiol have been shown in samples taken 12 h after administration of oral contraceptives in mid-menstrual cycle. Factors shown to be responsible for this variation include passage into the enterohepatic circulation, a variable first-pass effect, and changes in metabolism in the gut wall or liver due to diet, disease, smoking or administration of drugs. Phenobarbitone and the antibiotic rifampicin increase both oestrogen and progestogen metabolism in women and in experimental animals by increasing hepatic and gut wall metabolism. In animals, other antibiotics (ampicillin, neomycin and lincomycin) suppress the gut flora that normally hydrolyse steroid conjugates excreted in bile; enterohepatic circulation or oral contraceptive steroids is thus reduced and their plasma concentrations lowered by up to 90%. In the human, ampicillin has a variable but less dramatic effect on elimination of oral contraceptives. Samples of gut wall mucosa obtained from patients with coeliac disease are defective in their ability to metabolize oral contraceptives. Cigarette smokers eliminate ethinyloestradiol more rapidly than non-smokers; an increased production of reactive steroid metabolites may thus be a cause of vascular disease in women who smoke and take contraceptive steroids.

Animals↗
PubMed1993

Oral contraceptive use and the occurrence of gallstone disease--a case-control study.

BACKGROUND: We evaluated the hypothesized transient effect of oral contraceptive use on the occurrence of gallstone disease in a case-control study. METHODS: The study comprised 82 acute cases, and 249 general population controls, 28 elective cases, and 106 radiodiagnosis controls. Risk-period-specific rate ratios were estimated by logistic regression analysis. RESULTS: During the first 5 years after any year of oral contraceptive use (0- to 5-year risk period) the rate ratio was 1.6 (90% confidence interval, 0.83-2.95), and for the 6- to 10- and 11- to 20-year risk periods, 1.2 (0.67-2.13) and 1.1 (0.69-1.65), respectively. Further evaluation showed substantial confounding by other risk factors. After these were controlled for, the rate ratios were 1.1, 1.8, and 1.0 for the respective risk periods. When oral contraceptive use had been started recently (within 5 years before diagnosis) the rate ratio was 4.8 (0.79-29.7); recent oral contraceptive use was not associated with gallstone disease if preceded by 6 or more years of oral contraceptive use (rate ratio 0.8 (0.15-4.55)). CONCLUSIONS: The results are consistent with a transient effect of oral contraceptive use that does not accumulate beyond 10 years of use. However, the substantial confounding effect in our study raises the question whether the present and previously reported estimates of the effect may be biased by confounding.

Adult↗
PubMed1979

Pathologic effects of oral contraceptives.

The pathologic effects of oral contraceptives have been described in this paper and in other reviews [1, 5, 23, 35, 44, 48, 59, 80, 103, 114]. Approximately 10 million women currently use oral contraceptives in the United States. These drugs are beneficial both to the users and for population control. It is their effect on the health status of women who take them that must continue to have well-organized investigation so that more meaningful conclusions concerning their safety will permit continued use. In some instances, the pathologic effects of oral contraceptives make it necessary that new methods of contraception be found. Intensive research in this area is needed and judiciuos use of oral contraceptives must be maintained. A national registry should be formed to record and investigate the cases of women who die or have adverse reactions while taking these agents. A registry might identify associations no previously known to exist in patients taking oral contraceptives. It would serve to concentrate the data in one area so that more material would be available for the study of pathogenetic mechanisms. It would heighten patient and physician awareness of the untoward effects and increase the responsibilities of the women who take them to monitor their own health.

Blood Glucose↗
PubMed1995

Influence of ethinylestradiol-containing combination oral contraceptives with gestodene or levonorgestrel on caffeine elimination.

In a controlled clinical trial, the elimination of caffeine was examined in 20 healthy women prior to and during one cycle of treatment with either of two oral contraceptive formulations, one containing 0.075 mg gestodene and 0.03 mg ethinylestradiol and one containing 0.125 mg levonorgestrel and 0.03 mg ethinylestradiol. In addition, caffeine clearance was determined 1 month after the last intake of the oral contraceptives. Compared with pretreatment values, the clearance of caffeine was reduced by about 54% and 55% after one treatment cycle with gestodene- and the levonorgestrel-containing oral contraceptive, respectively. Other pharmacokinetic parameters of caffeine, such as tmax and Cmax, were not affected. Clearance values returned to pretreatment values 1 month after the last administration of the oral contraceptives. There was no difference in the reduction of caffeine clearance between contraceptive formulations. A small, but significant difference in the AUC(0-24 h) values of ethinylestradiol was noted between both preparations. There was no correlation between the AUC(model) values of caffeine and the AUC(0-24 h) values of ethinylestradiol. In the present study, a somewhat more pronounced effect on the elimination of caffeine was observed than in previous investigations, where several contraceptive steroids were administered only for a period of 2 weeks.

Administration, Oral↗
PubMed1990

Oral contraceptive administration, interfemale relationships, and sexual behavior in Macaca fascicularis.

The effects of oral contraceptive administration on the social relationships of adult female cynomolgus monkeys (Macaca fascicularis) were examined. Ten females were administered ethinyl estradiol/ethynodiol diacetate (Demulen), 10 were administered ethinyl estradiol/norgestrel (Ovral), and 10 served as a control group. The monkeys lived in social groups of 5 females each, and patterns of social interaction and social status were recorded. Interfemale relationships were also observed when a vasectomized male was placed in each social group for 50 min, once/week. During the latter observations, preliminary data on the effects of oral contraceptive treatment on sexual interaction were also collected. In the absence of the male, interfemale agonistic interactions and time spent alone were influenced by social status but not by oral contraceptive treatment. Time spent in passive body contact, an affiliative state, was reduced by Ovral treatment. In the presence of the male, dominant females aggressively interfered with the sexual interactions of subordinates. This aggression resulted in the termination of a greater proportion of the sexual interactions of subordinates than dominants in the control group only, indicating suppression of this type of interaction by oral contraceptive treatment. Other effects included a decreased frequency of ejaculation with Ovral-treated females. These results suggest that oral contraceptives may suppress certain types of female agonistic behavior (e.g., in the context of mate competition) and some oral contraceptives may interfere with sexual activity. More broadly, these findings indicate that intrasexual competition for access to mates may occur in females as well as males.

Aggression↗
PubMed1994

Multicenter study in Hungary with a 30 micrograms ethinylestradiol- and 150 micrograms desogestrel-containing monophasic oral contraceptive.

Among the countries in Central and Eastern Europe, Hungary has a high oral contraceptive prevalence rate. Until recently, however, Hungarian women have not had access to combined oral contraceptives with new, third-generation progestogens. Marvelon (30 micrograms ethinylestradiol and 150 micrograms desogestrel) was first introduced in 1981 in Western Europe and has, in a number of different studies, proven an effective and well-tolerated oral contraceptive with no effect on blood pressure and a favorable lipid profile. Marvelon was introduced in Hungary in October 1991. Prior to its introduction, a multicenter study was undertaken in Hungary with Marvelon to confirm the clinical results of studies from other countries. The present study confirmed Marvelon to be an effective, well-tolerated combined oral contraceptive with no relevant effect on blood pressure. Remarkable improvements were noted, especially with regard to side-effects, in switchers from other oral contraceptives. It is concluded that Marvelon is a valuable extension of the range of contraceptive methods available in Hungary.

Adolescent↗
PubMedDate not supplied

Emergency department post-coital contraception in Northern Ireland.

BACKGROUND: The granting of a licence to Levonelle as an emergency hormonal contraceptive in the Republic of Ireland may require accident and emergency (A&E) departments to formally provide such a service. This article outlines the experiences of a Northern Ireland A&E unit. AIMS: To examine the pattern of attendance of patients requesting emergency contraception at an A&E department and to assess if adequate standards of care are achieved. METHOD: Retrospective case note review of 100 patients attending the A&E department requesting emergency contraception. RESULTS: Sixty-one per cent of requests for emergency contraception were outside normal pharmacy opening hours. Seventy-seven per cent of these patients were less than 26 years old. Most (63%) attended within 24 hours of unprotected sexual intercourse. Forty-three per cent of the patients studied had used no contraception prior to this request. Recording of menstrual details and sexual behaviour as part of the consultation was variable. CONCLUSIONS: A&E departments receive requests for emergency hormonal contraception particularly from younger women (<25 years). A&E staff must have appropriate training and support to manage these consultations effectively.

Adolescent↗
PubMed2005

Oral contraceptive use and risk of breast cancer among women with a family history of breast cancer: a prospective cohort study.

Family history of breast cancer is an established risk factor for breast cancer. In addition, there is evidence that oral contraceptive use may be associated with a moderate increase in breast cancer risk. The three cohort studies that have investigated the relationship between oral contraceptive use and breast cancer risk among women with a family history of breast cancer have yielded mixed results, possibly due to the relatively small sample sizes employed and/or differences in the selection of covariates for inclusion in multivariate models. Therefore, we examined the association between oral contraceptive use and breast cancer risk in a large cohort study in Canada. The cohort consisted of the 27,318 women in the Canadian National Breast Screening Study who reported a family history of breast cancer on enrollment into the study. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow-up ending between 1998 and 2000, depending upon the province. During a mean of 16.0 years of follow-up, we observed 1707 incident cases of breast cancer among women with any history of breast cancer of which 795 cases occurred among women with a mother, sister, and/or daughter with breast cancer. Among women with any family history of breast cancer, ever use of oral contraceptives was associated with a 12% reduction in risk of breast cancer (95% confidence interval [CI]=0.73-1.07), and there was an inverse trend with increasing duration of use of borderline statistical significance (p(trend)=0.03). Although we also observed a 25% lower risk of breast cancer associated with oral contraceptive use of greater than 84 months versus never use among women with a first degree relative with breast cancer, this finding was not statistically significant (95% CI=0.47-1.19, p(trend)=0.48). Our data raise the possibility that relatively long duration of oral contraceptive use may be inversely associated with risk among women with a family history of breast cancer.

Adult↗
PubMed2006

Oral contraceptive use and risk of breast carcinoma in situ (United States).

OBJECTIVE: Our study assesses the impact of oral contraceptive use on breast carcinoma in-situ (BCIS) risk. METHODS: We conducted a population based case-control study of incident BCIS among black and white women ages 35-64 years residing in Los Angeles County. Case patients (n = 567) were newly diagnosed with BCIS and control participants (n = 614) were identified by random digit dialing between 1 March 1995 and 31 May 1998. All subjects were required to have had a mammogram in the 2 years before case diagnosis or control recruitment. Data were collected during in-person interviews. Multivariable logistic regression analyses provide estimates of odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Oral contraceptive use was not associated with risk of BCIS (OR = 1.04, 95% CI (0.76-1.42)). Risk did not increase with longer periods of use. No associations with BCIS risk were observed for oral contraceptive use before first term pregnancy, age at first oral contraceptive use, or for time since last use. Risk was not modified by estrogen dose, age, race, or parity. CONCLUSIONS: Our results are consistent with recent results on invasive breast cancer reported for the Women's Contraceptive and Reproductive Experiences Study and show no association between oral contraceptive use and risk of BCIS.

Adult↗
PubMed1976

Cigarette smoking, use of oral contraceptives, and myocardial infarction.

The excess risk of nonfatal myocardial infarction among users of oral contraceptives observed in England and Wales can be explained in terms of the high proportion of smokers in the study population. Among nonsmokers, the relative risk associated with the use of oral contraceptives is estimated to be 2 to 1, which is not statistically significant (P = 0.28, Fisher's exact probability test). The present analysis suggests that smoking be considered as another contraindication for the prescription of oral contraceptives. The results further indicate that those women who smoke as well as use oral contraceptives and are interested in reducing the risk of nonfatal mycardial infarction should be encouraged to give up smoking. The relative risk of nonfatal myocardial infarction associated with the use of oral contraceptives observed in a society can vary between 0.9 to 1 and 11.7 to 1, depending upon the proportion of smokers. From the public health point of view, the reduction in the excess risk of nonfatal myocardial infarction achieved by eliminating smoking is estimated to be much more than can be achieved by eliminating the use of oral contraceptives.

Adult↗
PubMed1987

Oral contraceptives, cigarette smoking and other factors in relation to arthritis.

The data on oral contraceptive use and arthritis in the Oxford-Family Planning Association contraceptive study have been analysed. For rheumatoid arthritis, the rate of first referral to hospital was 0.33 per 1000 woman-years in those who never used oral contraceptives (27 cases), 0.33 per 1000 woman-years in ex-users of oral contraceptives (29 cases) and 0.44 per 1000 woman-years in current users of oral contraceptives (22 cases). Likewise, there was no important association between oral contraceptive use and other forms of arthritis. An unexpected finding was a strong association between referral to hospital for rheumatoid arthritis and cigarette smoking; the rate in women never smoking was 0.27 per 1000 woman-years (34 cases) and in those smoking 15 or more cigarettes per day was 0.64 per 1000 woman-years (19 cases).

Adult↗
PubMed1989

"Sunday start" multiphasic oral contraception: ovulation prevention and delayed follicular atresia in primates.

Utilization of the "sunday start" method for oral contraceptive therapy can result in the initiation of oral contraceptive administration as late as day 6 of the ovarian/menstrual cycle. Potentially, "breakthrough" ovulations could occur due to rapid follicular progression, especially if the dominant follicle is overtly established prior to the onset of estrogen-progestin administration. Here, we examined the efficacy of two new oral contraceptive regimens on potential "breakthrough" ovulations in the first cycle of treatment begun on cycle days 1 or 6 in cynomolgus monkeys having normal menstrual cycles. Our endocrine findings show that follicular recruitment, and probably selection of the dominant follicle, had occurred by day 6 of the follicular phase. Both oral contraceptive treatments (Loestrin 5/7/9R, LoDose 5/7/9R, Parke-Davis) were effective in blocking preovulatory-like gonadotropin and estradiol surges as well as luteal phase progesterone elevations, whether treatment was begun on day 1 or day 6 of the menstrual cycle. Despite hormonal evidence of significant maturational progression, oral contraceptive administration successfully blocked the completion of follicular maturation, thereby sustaining contraceptive reliability, even in the initial cycle of treatment using a "sunday start" regimen. Under these conditions, dissolution of the failed dominant follicle within ovarian stroma may be characterized by delayed follicular atresia.

Animals↗
PubMed1989

Effect of oral contraceptives on adrenocorticotropin and growth hormone secretion following CRH and GHRH administration.

Previous investigations have demonstrated that basal ACTH plasma levels are reduced and that GH levels are either increased or unchanged in women taking oral contraceptives. The purpose of the present investigation was to determine the secretion of ACTH and GH following an intravenous infusion of human corticotropin releasing hormone (CRH) and human growth hormone releasing hormone (GHRH) in control women (N = 8) and in women taking a triphasic oral contraceptive (N = 9). The studies were initiated between 7:00 and 9:00 a.m. and all women were fasting. An intravenous catheter attached to a 3-way stopcock was used for blood sampling and to inject a bolus of CRH and GHRH (1 microgram/kg). Plasma samples were frozen immediately and stored at -70 degrees C until assayed for content of ACTH and GH by radioimmunoassay. The plasma levels of ACTH and GH increased following infusion of CRH and GHRH in all women. The mean plasma levels of growth hormone were not statistically different in oral contraceptive users compared to normal women. In contrast, ACTH plasma levels in oral contraceptive users were reduced approximately 25% overall, and significantly lower (p less than 0.04) at 120 minutes following the CRH infusion compared to controls. In conclusion, the GHRH-stimulated GH release was similar in normal women and oral contraceptive users. CRH-stimulated ACTH release was modestly reduced in oral contraceptive users compared to normal women suggesting that estrogens and progestogens may have a suppressive effect on the release of ACTH by the pituitary.

Adrenocorticotropic Hormone↗
PubMed1994

Oral contraceptive use and benign gallbladder disease; revisited.

An analysis is described of 482 women with benign gallbladder disease (surgically confirmed in 407) identified in the Oxford Family Planning Association contraceptive study. There was no significant overall association between oral contraceptive use and gallbladder disease (relative risk ever use to never use 1.1, 95% confidence interval 0.9 to 1.3). Likewise, duration of oral contraceptive use had no significant effect (relative risk 97 or more months use to never use 1.1, 95% confidence interval 0.8 to 1.5). There was no indication of any interaction between oral contraceptive use and body mass index or oral contraceptive use and age in the production of disease. It is concluded that it is unlikely that oral contraceptives are of either clinical or public health significance in relation to the occurrence of gallbladder disease.

Adult↗