Oral contraceptive use and risk of endometriosis

Objective To analyse the association between use of oral contraception and risk of pelvic endometriosis.
Design We compared use of oral contraception in women with and without endometriosis.
Participants Eligible for the study were women with primary or secondary infertility (   n = 393  ) or chronic pelvic pain (   n = 424  ). requiring laparoscopy, consecutively observed between September 1995 and January 1996 in 15 obstetrics and gynaecology departments in Italy.
Results Out of the 817 women included in the study, 345 had a diagnosis of endometriosis; 164 (47.5%) women with endometriosis and 139 (29.4%) without the disease reported ever using oral contraception. In comparison with never users the estimated odds ratios (OR) of endometriosis were 1.8 (95% CI 1.0–3.3) in current users and 1.6 (95% CI 1.1–2.4) in exusers. No clear relation emerged between duration of oral contraceptive use and risk of endometriosis. In comparison with never users, the OR was 1.8 (95% CI 1.1–3.0) for women reporting their last use of oral contraception < 5 years before interview and 1.5 (95% CI 0.9–2.5) for those reporting their last use >5 years before interview.
Conclusions The study suggests that oral contraception is associated with an increased risk of endometriosis but this finding is based on a selected population and cannot generalised to all women with endometriosis.     

Correcting misconceptions about oral contraceptives

Although the majority of American women believe that oral contraceptives can cause serious health problems such as cancer or heart disease, the scientific literature does not support these beliefs. Oral contraceptives actually protect against endometrial and ovarian cancer. The increased incidence of cardiovascular disease in oral contraceptive users, including myocardial infarction, appears to be caused by thrombosis and not atherosclerosis. The studies suggesting an increased risk of cardiovascular disease in oral contraceptive users were published in the late 1970s and therefore used a data base of women ingesting formulations containing 50 micrograms of estrogen or more. More recently published data involving healthy women taking mainly lower estrogen dose preparations suggest that there is no increased incidence of myocardial infarction or stroke. Nearly all published studies indicate that there is no increased risk of myocardial infarction in former users of oral contraceptives. Animal data actually suggest that oral contraceptives may have a protective effect against atherosclerosis, even in the presence of lowered high-density lipoprotein levels. The low-dose triphasic and monophasic formulations are effective, safe methods of contraception that can be used by most healthy women of reproductive age.     

Use of oral contraceptives and uterine fibroids: results from a case-control study

Objective To analyse the association between oral contraceptive use and the risk of uterine fibroids.
Design Participants We considered data collected in a case-control study on risk factors for uterine fibroids.
Participants We studied 843 women with uterine fibroids, whose clinical diagnosis dated back no more than two years. Controls were 1557 non-hysterectomised patients younger than 55 years admitted for acute, non-gynecological, non-hormonal, non-neoplastic conditions.
Results A total of 254 cases (30.1 %) and 360 controls (23.1 %) reported ever using oral contraceptives: the odds ratio (OR) for ever vs never users was 1–1 (95% CI 0-8–1.3). The risk in current users was below unity when compared with never users (OR 0.3,95% CI 0.2–0.6), while ex-users had a risk of fibroids comparable with never users (OR 1. I, 95% CI 0.9–1.4). The risk of uterine fibroids decreased with duration of oral contraceptive use: compared with never users, the estimated OR was 0.8 (95% CI 0.5–1.2) in ever users for four to six years and 0.5 (95% CI 0.349) for seven years or more (trend = 4.6,   P = 0.03  ).
Conclusions Although the role of selection bias should be carefully evaluated, the present data suggest that uterine fibroids should not be considered a contra-indication for oral contraceptive use.     

Contraception for women in selected circumstances

OBJECTIVE: To review new evidence regarding ten controversial issues in the use of contraceptive methods among women with special conditions and to present World Health Organization recommendations derived in part from this evidence. DATA SOURCES: We searched MEDLINE and PREMEDLINE databases for English-language articles, published between January 1995 and December 2001, for evidence relevant to ten key contraceptive method and condition combinations: combined oral contraceptive (OC) use among women with hypertension or headaches, combined OC use for emergency contraception and adverse events, progestogen-only contraception use among young women and among breast-feeding women, tubal sterilization among young women, hormonal contraception and intrauterine device use among women who are human immunodeficiency virus (HIV) positive, have AIDS, or are at high risk of HIV infection. Search terms included: "contraception," "contraceptives, oral," "progestational hormones," "medroxyprogesterone-17 acetate," "norethindrone," "levonorgestrel," "Norplant," "contraceptives, postcoital," "sterilization, tubal," "intrauterine devices," "hypertension," "stroke," "myocardial infarction," "thrombosis," "headache," "migraine," "adverse effects," "bone mineral density," "breast-feeding," "lactation," "age factors," "regret," and "HIV." STUDY SELECTION: From 205 articles, we identified 33 studies published in peer-reviewed journals that specifically examined risks of contraceptive use among women with pre-existing conditions. TABULATION, INTEGRATION, AND RESULTS: Combined OC users with hypertension appear to be at increased risk of myocardial infarction and stroke relative to users without hypertension. Combined OC users with migraine appear to be at increased risk of stroke relative to nonusers with migraine. The evidence for the other eight method and condition combinations was either insufficient to draw conclusions or identified no excess risk. CONCLUSION: Of ten contraceptive method and condition combinations assessed, the evidence supported an increased risk of cardiovascular complications with combined OC use by women with hypertension or migraine. As new evidence becomes available, assessment of risk and recommendations for use of contraceptive methods can be revised accordingly.     

Smoking and Contraception

Efforts by governments and public health bodies largely have been unable to reduce cigarette consumption by Canadians. Women who smoke (29% of women in the reproductive years) have reduced fertility and an increased risk of short-term and long-term cardiovascular disease. Women who have used oral contraceptive preparations in the past appear to have no increased cardiovascular risk, but current users carry an increased risk of thrombosis. The degree of risk is proportional to the estrogen dose of the preparation used. Women who smoke cigarettes and concurrently use oral contraceptives increase their risk of myocardial infarction beyond that of using either agent alone; the risk is increased in heavier smokers and in women over age 35. There is no effect of smoking on other forms of contraception.     

Oral contraceptive use and risk of endometriosis. Italian Endometriosis Study Group.

OBJECTIVE: To analyse the association between use of oral contraception and risk of pelvic endometriosis. DESIGN: We compared use of oral contraception in women with and without endometriosis. PARTICIPANTS: Eligible for the study were women with primary or secondary infertility (n = 393) or chronic pelvic pain (n = 424), requiring laparoscopy, consecutively observed between September 1995 and January 1996 in 15 obstetrics and gynaecology departments in Italy. RESULTS: Out of the 817 women included in the study, 345 had a diagnosis of endometriosis; 164 (47.5%) women with endometriosis and 139 (29.4%) without the disease reported ever using oral contraception. In comparison with never users the estimated odds ratios (OR) of endometriosis were 1.8 (95% CI 1.0-3.3) in current users and 1.6 (95% CI 1.1-2.4) in ex-users. No clear relation emerged between duration of oral contraceptive use and risk of endometriosis. In comparison with never users, the OR was 1.8 (95% CI 1.1-3.0) for women reporting their last use of oral contraception < 5 years before interview and 1.5 (95% CI 0.9-2.5) for those reporting their last use > or = 5 years before interview. CONCLUSIONS: The study suggests that oral contraception is associated with an increased risk of endometriosis but this finding is based on a selected population and cannot generalised to all women with endometriosis.     

Cardiovascular issues with oral contraceptives: evidenced-based medicine

Recent studies of current oral contraceptives indicate that the risk of cardiovascular sequelae is low in young (age 20-24 years) reproductive-aged women. Venous thromboembolism remains the one event that occurs in users independent of the presence of risk factors. However, the attributable risk is small, in the range of 7 to 18 events per 100,000 women annually. This risk is proportional to estrogen dose until the level of 30-35 microg is reached; type of progestin may also influence risk, though recent studies are controversial. Modifiable risk factors for venous thromboembolism include the presence of hemostatic disorders, especially factor V Leiden, and perhaps obesity. Stroke is even more uncommon, with an attributable risk of about 1.5 events per 100,000 women annually. Cigarette smoking and hypertension are modifiable risk factors for both ischemic and hemorrhagic stroke; use of preparations with 50 microg of estrogen or higher and migraine headaches are risk factors for ischemic stroke. Eliminating risk factors among users substantially reduces the risk of ischemic stroke and virtually eliminates the risk of hemorrhagic stroke. Myocardial infarction is rare among young women, occurring at a rate of about 0.2 event per 100,000 women annually. Oral contraceptive users who are non-smoking and normotensive do not have an increased risk of myocardial infarction. However, the presence of these risk factors along with age acts synergistically to increase the risk among oral contraceptive users.     

Use of oral contraceptives in women of older reproductive age

Evidence of increased risk for cardiovascular disease in oral contraceptive users of older reproductive age is based on early data involving formulations containing higher doses of estrogen and progestin than those in use today. In addition, early studies included patients who would not receive oral contraceptives with today's more stringent prescribing criteria. When these data were carefully analyzed, a significant increase in myocardial infarction was noted only in oral contraceptive users with concemitant risk factors for cardiovascular disease. Analysis of other studies also showed a significant increase in the incidence of cardiovascular disease and mortality only in oral contraceptive users older than age 35 years who smoked. A recent long-term cohort study of women without risk factors for cardiovascular disease who mainly used oral contraceptives containing ≤50 μg estrogen showed no increased risk of myocardial infarction or cerebrovascular accident with oral contraceptive use. Use of oral contraceptives containing <50 μg estrogen has not been shown to be associated with an increased risk of cardiovascular disease in healthy, nonsmoking women 35 to 45 years of age.     

A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study

Objective To assess the possible benefit of hormone replacement therapy (HRT) in the secondary prevention of ischaemic heart disease.
Design A prospective randomised trial of transdermal HRT in women with definite ischaemic heart disease.
Setting A regional cardiac unit.
Population Postmenopausal women with angiographically ischaemic heart disease.
Methods A total of 255 postmenopausal women with angiographically proven ischaemic heart disease were recruited and randomised; 134 were treated with transdermal HRT and 121 acted as controls. The women were seen at six monthly intervals. The primary end points, which were determined by a blinded assessor, were admission to hospital with unstable angina, proven myocardial infarction or cardiac death. A total of 53 (40%) patients withdrew from the HRT group and eight (7%) from the control group. The mean duration of follow up was 30.8 months.
Main outcome measures Admission to hospital with unstable angina, proven myocardial infarction or cardiac death.
Results During follow up, there were 53 primary end-point events in the HRT group and 37 in the control group. Using an intention-to-treat analysis, the primary end-point event rate was 15.4 events per 100 patient years for the HRT group compared with 11.9 for the control group (event rate ratio 1.29 (95% CI 0.84–1.95,   P = 0.24  )). Using a per-protocol analysis, there was an event rate ratio of 1.49 (  0.93–2.36, P = 0.11  ) for the HRT arm compared with the control arm. Particularly during the first two years of follow up, the HRT group had a higher, but not statistically significant, event rate than the control group.
Conclusion Our findings suggest that transdermal HRT should not be commenced for the purpose of secondary prevention in postmenopausal women with angiographically proven ischaemic heart disease.     

To have or not to have a pregnancy

A follow-up study of more than 65,000 healthy women aged 15 to 44 was conducted to assess the association between oral contraceptive use and thromboembolism, stroke, or nonfatal myocardial infarction from 1980 through 1982 at Group Health Cooperative of Puget Sound. A positive association existed between current oral contraceptive use and venous thromboembolism (rate ratio equals 2.8), but there was no positive association between current oral contraceptive use and stroke or myocardial infarction.     

Is oral contraceptive use still associated with an increased risk of fatal myocardial infarction? Report of a case-control study.

OBJECTIVE--To investigate the association between fatal myocardial infarction and use of modern low-dose oral contraceptives. DESIGN--A case-control study. SETTING--General practices throughout England and Wales. SUBJECTS--161 women aged under 40 dying from myocardial infarction during 1986-1988. Living controls (2 per case), matched for age and marital status, were chosen from general practice lists. Information was collected during structured interviews with general practitioners, and from postal questionnaires sent to surviving partners of the cases and to control women. MAIN OUTCOME MEASURES--Mortality from myocardial infarction in relation to many risk factors, notably oral contraception, as measured by relative risk. RESULTS--After allowing for the confounding effects of medical risk factors and for surgical sterilization, the overall relative risk associated with both current and past use of oral contraceptives was estimated to be 1.9 (95% CI 0.7 to 4.9, and 1.0 to 3.5 respectively). The relative risk associated with current use of preparations containing 50 micrograms of oestrogen, however, was estimated to be 4.2 (0.5 to 39.2). At least some of the relative risk associated with oral contraceptive use is likely to be attributable to the confounding effect of cigarette smoking, but it is impossible to estimate how much from the available data. CONCLUSIONS--If there was an increased risk of fatal myocardial infarction associated with oral contraceptive use in 1986-1988 it is likely to have been less than two-fold; in this study risks were slightly, but not significantly, elevated with both current and previous use. It may be that any increase in risk is associated solely with the older combined preparations containing 50 micrograms of oestrogen.     

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.     

Effects of smoking and oral contraception on plasma beta-carotene levels in healthy women

Oral contraceptive use and smoking have been known to affect plasma vitamin levels. Total carotenoids have been studied with spectrophotometry, a relatively insensitive technique. In this study plasma concentrations of beta-carotene and retinol were measured in coded samples by sensitive high-pressure liquid chromatography in a cross-sectional study of 149 normal healthy women attending a family planning clinic. At the time of recruitment in the morning, a general health questionnaire was administered for patient age, methods of contraception, smoking habits, and food intake at breakfast. Of the 149 enrolled volunteers, 88 were oral contraceptive users and 61 were not users. Among users, 21 smoked cigarettes, and there were 18 smokers among nonusers. Oral contraceptive users had significantly lower plasma concentrations of beta-carotene (p less than 0.001) and higher retinol levels (p less than 0.0001). Plasma beta-carotene or retinol levels did not differ among users of intrauterine contraceptive devices or barrier methods of contraception. No association was noted between the plasma levels of these two micronutrients and age greater than or less than 30 years. Cigarette smoking alone was associated with significantly reduced plasma beta-carotene levels in nonusers (p less than 0.001). Combined cigarette smoking and oral contraceptive usage were associated with low plasma beta-carotene levels; the results appear to be additive. These findings suggest a possible synergistic effect on plasma beta-carotene levels from the use of both cigarette smoking and oral contraception.     

Long-term treatment with combined oral contraceptives and cigarette smoking associated with impaired activity of tissue plasminogen activator

The fibrinolytic activity in vein walls (FAV) was determined by a semi-quantitative fibrin slide technique in a group of 68 healthy middle-aged women consisting of 22 healthy controls, 19 non-smoking contraceptive pill users and 27 cigarette-smoking non-users. Significantly decreased FAV was demonstrated in pill users because of high frequency of low values among women using combined oral contraceptives (OC) for more than 5 years. Significantly lower FAV was also recorded in smoking non-users, among whom low FAV values were found mainly in heavy smokers. However, no effect of OC usage for less than 5 years was observed, neither did smoking of less than 10 cigarettes daily influence FAV. Thus, the two well-known risk groups with respect to circulatory diseases, long-term contraceptive users and heavy smokers, included the vast majority of middle-aged women with impaired plasminogen activator activity.     

Bacterial flora of the cervix in women using different methods of contraception

Bacteriologic culture samples were taken from the cervix in three groups of 10 healthy, sexually active women using barrier contraception, oral contraceptives, or a levonorgestrel-releasing intrauterine contraceptive device. Culture samples for Candida albicans and Trichomonas vaginalis were taken, a cytologic vaginal smear was obtained, and an amine sniff test was performed; these were in addition to a routine gynecologic examination. Multiple bacteria were isolated from the cervix in women using oral contraceptives or an intrauterine contraceptive device, whereas lactobacilli alone dominated the flora of women using barrier contraception. Significantly more anaerobic bacteria were isolated from the cervix in oral contraceptive and intrauterine contraceptive device users when compared with the barrier method users. Symptoms and findings evident of anaerobic vaginosis were associated with the occurrence of anaerobic bacteria in the cervix of three patients using the intrauterine contraceptive device. The results showed that the cervical bacterial flora in sexually active healthy women is rich in anaerobes that can be regarded as a normal finding in women using oral contraceptives or intrauterine contraceptive devices. Barrier contraception with a condom prevents this anaerobic shift and maintains a lactobacilli-dominated flora in the cervix.     

Is the intrauterine device appropriate contraception for HIV-1-infected women?

Objective To assess whether the risk of complications is higher in HIV-1-infected women compared with non-infected women in the two years following insertion of the intrauterine contraceptive device.
Design Prospective cohort study.
Population Six hundred and forty-nine women (156 HIV-1-infected, 493 non-infected) in Nairobi, Kenya who requested an intrauterine contraceptive device and met local eligibility criteria.
Methods We gathered information on complications related to the use of the intrauterine contraceptive device, including pelvic inflammatory disease, removals due to infection, pain or bleeding, expulsions, and pregnancies at one, four, and 24 months after insertion by study physicians masked to participants' HIV-1 status. Cox regression was used to estimate hazard ratios.
Results Complications were identified in 94 of 636 women returning for follow up (14.7% of HIV-1-infected, 14.8% of non-infected). The incidence of pelvic inflammatory disease was rare in both infected (2.0%) and non-infected (0.4%) groups. Multivariate analyses suggested no association between HIV-1 infection and increased risk of overall complications (hazard ratio=1.0; 95% CI 0.6-1.6). Infection-related complications (e.g. any pelvic tenderness, removal for infection or pain) were also similar between groups (10.7% of HIV-1-infected, 8.8% of non-infected; P =0.50), although there was a non-significant increase in infection-related complications among HIV-1-infected women with use of the intrauterine contraceptive device longer than five months (hazard ratio=1.8; 95% CI 0.8-4.4). Neither overall nor infection-related complications differed by CD4 (immune) status.
Conclusions HIV-1-infected women often have a critical need for safe and effective contraception. The intrauterine contraceptive device may be an appropriate contraceptive method for HIV-1-infected women with ongoing access to medical services.     

Considerations for contraception in women with cardiovascular disorders

Women with hypertension, angina pectoris, or mitral valve prolapse require special considerations when selecting an appropriate method of contraception. All three effective, reversible options (oral contraceptives, intrauterine devices, or progestin implants) carry some degree of added risk for these patient populations. However, pregnancy itself presents certain risks and, in the event of contraceptive failure, certain women with these disorders are at increased risk of developing serious cardiovascular sequelae that affect both mother and fetus. These negative effects can carry far into the neonatal period. This article describes the risk/benefit profiles of the currently available contraceptive options relative to their potential impact in these compromised women. (Ann J OBSTET GYNECOL 1993;168:2006-11.)     

The influence of method of contraception and cigarette smoking on menstrual patterns

Summary. Self-perceived menstrual patterns have been investigated in a sample of 2115 women aged 18–9 years using a postal questionnaire. Seven aspects of 'abnormal' menstruation were denned: prolonged periods, heavy periods, frequent periods, irregular periods, intermenstrual bleeding, painful periods and severe premenstrual syndrome. Women who used oral contraceptives were less likely than other women to report any of the seven menstrual abnormalities except for intermenstrual bleeding and severe premenstrual tension. Women who used an intrauterine contraceptive device (IUCD) reported prolonged, heavy, and frequent periods and intermenstrual bleeding more often than other women, but they did not report painful periods with undue frequency. Women who had had a tubal sterilization generally reported menstrual patterns similar to, or slightly less favourable than, women using no contraception or contraceptive methods other than the pill or the IUCD. There was a significant association between smoking habits and each of the abnormal menstrual patterns except for severe premenstrual tension. In every case, the effect of smoking was unfavourable and in almost every case, current smokers reported the worst experience, with ex-smokers occupying an intermediate position. We believe that these data are of considerable clinical significance and that they offer a basis for a conservative approach to managing menstrual disorders in some women.     

Contraception at 40

During forty, fertility decreases but the risk of spontaneous pregnancy is not negligible, so contraception for forty years old women remains necessary. Several contraceptive methods are available: local contraception, intra-uterine devices, hormonal contraception. Progestogen-only pills, microdosed and continuously administered are to be avoided at this time of life because they can result in hyperestrogenic adverse events. Progestin implants are interesting if the woman presents contraindication with estrogens or if she is non compliant with oral contraceptives. Oral contraceptive use is associated with numerous benefits during forty: it controls properly cycles and menstruations, it decreases bone loss and it decreases gynaecological disorders and risk of endometrial and ovarian cancer... But cardiovascular risk (venous and arterial thrombo-embolism) remains increased, whatever oral contraceptive is used, second or third generation, and in spite of lower dose of ethinylestradiol, even if a trend towards the decrease of this risk is observed. Contraindication for one kind of oral contraceptive means contraindication for all oral contraceptives and necessarily bare respect of this. These contraindications led to contraceptive use of progestin with antigonadotropic activity; however if pregnane derivatives are devoid of any deleterious metabolic effects, they have no indication for contraception in their marketing authorization.     

Pille und Krebsrisiko

Background

Approximately 70–75?% of women between 18 and 50 years of age in Germany use one of many different contraceptive methods and more than half of them use combined hormonal oral contraceptives. These women demand two things from contraception: high contraceptive safety and low side effects. Thromboembolic and cardiovascular risks were recently under broad discussion in the media but the question whether hormonal contraceptives modify the risk for cancer is an important issue for many women and their doctors as well. This applies especially to women with a genetic disposition for malignant diseases.

Aim

How is cancer risk modified in women with current or recent hormonal contraceptive use? The dependency of risk on duration of use, intervals between intake and use in particularly hormone-sensitive phases of life (such as puberty) are described.

Material and methods

State of the art information is presented and discussed in view of the results of current meta-analyses, as well as national and international guidelines.

Results

Current meta-analyses showed a significant risk reduction for endometrial and ovarian cancer in combined oral contraceptive users with increased risk reduction following increased duration of use. No significant increase for risk of breast cancer was reported. No uniform data on risk modification for cancer of the cervix uteri and colon cancer in current users of hormonal contraceptives are available. This applies not only for the general population but also for carriers of breast cancer (BRCA) mutations.

Conclusion

For women without a hormone-dependent tumor or disease in the medical history, there is no contraindication for hormonal contraception due to elevated cancer risk. However, the data are not sufficient to justify their use exclusively for chemoprevention, such as for ovarian cancer in high-risk patients.