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Objective To see if the mortality risk among women who have used oral contraceptives differs from that of never users.

Design Prospective cohort study started in 1968 with mortality data supplied by participating general practitioners, National Health Service central registries, or both.

Setting 1400 general practices throughout the United Kingdom.

Participants 46 112 women observed for up to 39 years, resulting in 378 006 woman years of observation among never users of oral contraception and 819 175 among ever users.

Main outcome measures Directly standardised adjusted relative risks between never and ever users for all cause and cause specific mortality.

Results 1747 deaths occurred in never users of oral contraception and 2864 in ever users. Compared with never users, ever users of oral contraception had a significantly lower rate of death from any cause (adjusted relative risk 0.88, 95% confidence interval 0.82 to 0.93). They also had significantly lower rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynaecological cancers combined; all circulatory disease; ischaemic heart disease; and all other diseases. They had higher rates of violent deaths. No association between overall mortality and duration of oral contraceptive use was observed, although some disease specific relations were apparent. An increased relative risk of death from any cause between ever users and never users was observed in women aged under 45 years who had stopped using oral contraceptives 5-9 years previously but not in those with more distant use. The estimated absolute reduction in all cause mortality among ever users of oral contraception was 52 per 100 000 woman years.

Conclusion Oral contraception was not associated with an increased long term risk of death in this large UK cohort; indeed, a net benefit was apparent. The balance of risks and benefits, however, may vary globally, depending on patterns of oral contraception usage and background risk of disease.

Background

Although many individuals have multiple lifestyle risk factors, few studies have investigated the impact of lifestyle risk factor combinations among women.

Aim

To investigate the relationship between individual and combinations of lifestyle risk factors in middle-aged women with subsequent mortality, and to estimate the associated population attributable risks.

Design of study

Prospective cohort study.

Setting

Royal College of General Practitioners' (RCGP) Oral Contraception Study, UK.

Method

In 1994–1995, women remaining under follow-up in the RCGP Oral Contraception Study were sent a lifestyle survey, from which modifiable risk factors were identified: pack-years smoked, physical inactivity, never drinking versus consuming at least 7 units of alcohol weekly, and being underweight, overweight, or obese. The cohort was followed to December 2006 or death. Population attributable risks were calculated.

Results

Of 10 059 women studied, 896 died. Pack-years smoked (11–20 years: adjusted hazard ratio [HR] = 1.82, 95% confidence interval [CI] = 1.46 to 2.27; >20 years: adjusted HR = 2.34, 95% CI = 2.00 to 2.74); never drinking alcohol (adjusted HR = 1.66, 95% CI = 1.34 to 2.05); being underweight (adjusted = HR 1.66, 95% CI = 1.03 to 2.68); and physical inactivity (<15 hours/week: adjusted HR = 1.73, 95% CI = 1.46 to 2.04) were significantly associated with mortality compared with their respective reference group. Women with multiple lifestyle risk factors had higher mortality risks than those reporting one factor. The population attributable risk of the combination of smoking, physical inactivity, body mass index outside normal range, and alcohol (never drinking or excess intake) was 59% (95% CI = 31% to 78%).

Conclusion

Assuming a causal relationship between lifestyle and mortality, avoidance of four lifestyle risk factors would have prevented 60% of the deaths. The importance of avoiding smoking and undertaking physical inactivity during midlife should continue to be emphasised.

Objective

To describe the long term effects of the use of oral contraceptives on mortality.

Design

Cohort study with 25 year follow up. Details of oral contraceptive use and of morbidity and mortality were reported six monthly by general practitioners. 75% of the original cohort was “flagged” on the NHS central registers.

Setting

1400 general practices throughout Britain.

Subjects

46 000 women, half of whom were using oral contraceptives at recruitment in 1968-9. Median age at end of follow up was 49 years.

Main outcome measures

Relative risks of death adjusted for age, parity, social class, and smoking.

Results

Over the 25 year follow up 1599 deaths were reported. Over the entire period of follow up the risk of death from all causes was similar in ever users and never users of oral contraceptives (relative risk=1.0, 95% confidence interval 0.9 to 1.1; P=0.7) and the risk of death for most specific causes did not differ significantly in the two groups. However, among current and recent (within 10 years) users the relative risk of death from ovarian cancer was 0.2 (0.1 to 0.8; P=0.01), from cervical cancer 2.5 (1.1 to 6.1; P=0.04), and from cerebrovascular disease 1.9 (1.2 to 3.1, P=0.009). By contrast, for women who had stopped use ⩾10 years previously there were no significant excesses or deficits either overall or for any specific cause of death.

Conclusion

Oral contraceptives seem to have their main effect on mortality while they are being used and in the 10 years after use ceases. Ten or more years after use ceases mortality in past users is similar to that in never users.

Key messagesThis 25 year follow up of 46 000 UK women found a decrease in mortality from ovarian cancer and an increase in mortality from circulatory diseases and cervical cancer among women were using oral contraceptives or had used them in the past 10 years10 or more years after stopping use mortality was similar in past users and never usersOral contraceptives seem to have their main effect on mortality mainly while they are being used and in the 10 years after stopping useThere is little evidence to suggest any persistent adverse effect 10 or more years after use of oral contraceptives ceases

The incidence of breast cancer was studied among women taking part in the continuing cohort study organised by the Royal College of General Practitioners. An overall relative risk of 1.19 (not significant) was found in those who had used oral contraceptives. The risk ratio in women under 35 years old was 2.81, but this too was not significant. There was evidence that the estimated increased risk for younger women could be a chance occurrence. No convincing evidence of any adverse effects of oral contraceptives on breast cancer has been shown, but because of the long latent period of this tumour there is a need for longer observation.

STUDY OBJECTIVE: To determine whether changes in smoking status among women recruited for the Royal College of General Practitioners' Oral Contraception Study affected previous risk estimates for myocardial infarction. DESIGN: (1) Postal survey between November 1994 and July 1995 of women still under general practitioner observation. Validation of the smoking information supplied by the women on the questionnaire by comparison with that reported by the general practitioner at recruitment to the main study. (2) Nested case-control study of 103 cases of myocardial infarction, matched with 309 controls, to see if different risk estimates were obtained when smoking status at recruitment or smoking status at time of event were used in the analysis. SETTING: 650 general practices throughout the United Kingdom. PARTICIPANTS: 10,073 women who responded to the questionnaire (85.4% of 11,797 sent out). MAIN RESULTS: There was good agreement between smoking information recorded by the general practitioner at recruitment and that supplied retrospectively by respondents to the questionnaire. The risk estimates for myocardial infarction associated with use of combined oral contraceptives (COCs) were almost identical irrespective of whether smoking status at recruitment or at time of event was used for the statistical adjustment. This was because few women stopped smoking while also using COCs. In fact, fewer regular smokers who have ever used COCs reported stopping smoking than never users. The risk estimates for myocardial infarction associated with smoking were smaller when smoking habits at recruitment was used than when smoking habits at time of event was used. CONCLUSIONS: Previous results from the Oral Contraception Study regarding the effects of COCs are unlikely to have been biased by changes in the smoking habits of the cohort, but the effects of smoking have probably been underestimated. There is still a need for effective health education regarding the risks associated with smoking, particularly among users of COCs.

 

A comparison has been made between the coding of the cause of death by (a) the Royal College of General Practitioners (RCGP) during the Oral Contraception Study and (b) the Office of Population Censuses and Surveys (OPCS) or the General Register Office for Scotland (GRO) on death certificates for the same subjects. Broad grouping of the International Classification of Diseases (ICD) showed close agreement between RCGP and OPCS or GRO coding for all deaths which occurred from the start of the Oral Contraception Study in 1968 up to December 1978. Moreover, where discrepancies occurred there were no systematic differences between ever-users of oral contraceptive and non-users. Detailed examinations of discrepancies in the coding of the causes of those deaths included in the RCGP publication of October 1977 shows that our previous estimate of mortality risk associated with oral contraceptives would not be materially altered by the use of death certificate information.

Objective To examine the absolute risks or benefits on cancer associated with oral contraception, using incident data.

Design Inception cohort study.

Setting Royal College of General Practitioners' oral contraception study.

Participants Directly standardised data from the Royal College of General Practitioners' oral contraception study.

Main outcome measures Adjusted relative risks between never and ever users of oral contraceptives for different types of cancer, main gynaecological cancers combined, and any cancer. Standardisation variables were age, smoking, parity, social class, and (for the general practitioner observation dataset) hormone replacement therapy. Subgroup analyses examined whether the relative risks changed with user characteristics, duration of oral contraception usage, and time since last use of oral contraception.

Results The main dataset contained about 339 000 woman years of observation for never users and 744 000 woman years for ever users. Compared with never users ever users had statistically significant lower rates of cancers of the large bowel or rectum, uterine body, and ovaries, tumours of unknown site, and other malignancies; main gynaecological cancers combined; and any cancer. The relative risk for any cancer in the smaller general practitioner observation dataset was not significantly reduced. Statistically significant trends of increasing risk of cervical and central nervous system or pituitary cancer, and decreasing risk of uterine body and ovarian malignancies, were seen with increasing duration of oral contraceptive use. Reduced relative risk estimates were observed for ovarian and uterine body cancer many years after stopping oral contraception, although some were not statistically significant. The estimated absolute rate reduction of any cancer among ever users was 45 or 10 per 100 000 woman years, depending on whether the main or general practitioner observation dataset was used.

Conclusion In this UK cohort, oral contraception was not associated with an overall increased risk of cancer; indeed it may even produce a net public health gain. The balance of cancer risks and benefits, however, may vary internationally, depending on patterns of oral contraception usage and the incidence of different cancers.

To determine the pattern of risk factors for acute myocardial infarction associated solely with women a nested case-control study was carried out on cohort data collected during the Royal College of General Practitioners' oral contraception study. Smoking (adjusted relative risk 1.7 for light smokers and 4.3 for heavy smokers), hypertension (2.4), toxaemia of pregnancy (2.8), and diabetes mellitus (6.9) were associated with a significantly increased risk of myocardial infarction. There was no significant trend of risk with social class. Current use of the pill increased the risk only among women who also smoked (relative risk 20.8 for heavy smokers). Previous use of the pill did not influence the risk of myocardial infarction. If heavy smokers also had a history of toxaemia of pregnancy their risk of myocardial infarction was further increased (relative risk 41.0). Other variables associated solely with women, such as parity, hysterectomy, and hormone replacement therapy, had little effect on the risk of having a myocardial infarction. Overall, smoking was the most important independent risk factor and had a strong influence on risks associated with other factors.

The effects of cigarette smoking and parity on the development of symptomatic gall bladder disease remain controversial. These relations have been examined in a cohort of 46,000 women followed for up to 19 years during the Royal College of General Practitioners' (RCGP) oral contraception study. During follow up, 1087 women were recorded as experiencing their first ever episode of symptomatic cholelithiasis (International Classification of Diseases, 8th revision (ICD-8) 574) or cholecystitis (ICD-8 575). Smokers were more likely to develop symptomatic gall bladder disease than non-smokers (relative risk 1.19; 95% confidence intervals (95% CI) 1.06 to 1.34) and there was a significant trend with the number of cigarettes smoked daily (test for trend chi 2 = 7.58, p < 0.01). This relation was most apparent among never users of oral contraceptives, although similar trends were found among current and former users. A significant direct relation between symptomatic gall bladder disease and parity was also found (test for trend chi 2 = 21.89, p < 0.001). When all were examined together a trend of increasing risk with lower social class was also found (test for trend chi 2 = 5.72, p = 0.02). Current users of oral contraceptives had a moderately increased risk of symptomatic gall bladder disease (relative risk 1.15; 95% CI 0.99 to 1.34), unlike former users (relative risk 1.03; 95% CI 0.90 to 1.18). These results suggest that smoking and parity are important risk factors for the development of symptomatic gall bladder disease in women.

Ovarian cancer is the leading cause of reproductive cancer death in U.S. women. This high mortality rate is due to the lack of early detection methods and ineffectiveness of therapy for advanced disease. Until more effective screening methods and therapies are developed, chemoprevention strategies are warranted. The hen has a high spontaneous prevalence of ovarian cancer and has been used as a model for studying ovarian cancer chemoprevention. In this study, we used the hen to determine the effect of progestin alone, estrogen alone, or progestin and estrogen in combination (as found in oral contraceptives) on ovarian cancer prevalence. We found that treatment with progestin alone and in combination with estrogen decreased the prevalence of ovarian cancer. A significant risk reduction of 91% was observed in the group treated with progestin alone (risk ratio 0.0909: 95% confidence interval 0.0117-0.704) and an 81% reduction was observed in the group treated with progestin plus estrogen (risk ratio 0.1916: 95% confidence interval 0.043-0.864). Egg production was also significantly reduced in these treatment groups compared to control. We found no effect of progestin, either alone or in combination with estrogen, on apoptosis or proliferation in the ovary, indicating that this is not the likely mechanism responsible for the protective effect of progestin in the hen. Our results support the use of oral contraceptives to prevent ovarian cancer and suggest that ovulation is related to the risk of ovarian cancer in hens and that other factors, such as hormones, more than likely modify this risk.

Background

Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa).

Objectives

To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality.

Methods

The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs, intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and mortality. These analyses were performed by individual nations and by continents worldwide.

Results

OC use was significantly associated with prostate cancer incidence and mortality in the individual nations worldwide (r=0.61 and r=0.53, respectively; p<0.05 for all). PCa incidence was also associated with OC use in Europe (r=0.545, p<0.05) and by continent (r=0.522, p<0.05). All other forms of contraceptives (ie, intra-uterine devices, condoms or vaginal barriers) were not correlated with prostate cancer incidence or mortality. On multivariable analysis the correlation with OC was independent of a nation's wealth.

Conclusion

A significant association between OCs and PCa has been shown. It is hypothesised that the OC effect may be mediated through environmental oestrogen levels; this novel concept is worth further investigation.

Article summary

Article focus

Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa).

Associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs) have been examined.

It is hypothesised that OC by-products may cause an environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality.

Key messages

In this hypothesis generating ecological study, a significant association between female use of OCs and prostate cancer has been demonstrated.

Strengths and limitations of this study

This study is an ecological study and thus has significant limitations with respect to causal inference. It must be considered hypothesis generating, and thought provoking.

BACKGROUND: So far, no-one has attempted to evaluate the overall balance of serious, but not necessarily fatal, disease among a cohort of oral contraceptive users. AIM: To emprirically assess the balance of risk of serious illness among a cohort of oral contraceptive users followed up for up to 28 years. METHODS: Oral contraceptive-associated serious disease was defined as that which is often life-threatening and/or associated with long-term disability, and which has been found, or postulated, to be associated with use of combined oral contraceptives. Data from the Royal College of General Practitioners' (RCGP) Oral Contraception Study were examined to determine the rate of such conditions during 335,181 woman-years of observation in 'ever users' and 228,727 woman-years in 'never users'. The rates were standardized for age, parity, social class, and smoking. RESULTS: Compared with never users, ever users had a small increased risk of any serious disease (relative risk = 1.17; 95% confidence interval = 1.09-1.25). Ever users had an excess risk of cerebrovascular disease, pulmonary embolism, and venous thromboembolism, and reduced risk of ovarian and endometrial cancer. The increased risk was seen only in younger women; by the age of 50, ever users had the same risk as never users. The risk appeared to be confined to women using older oral contraceptives containing 50 micrograms or more of oestrogen. CONCLUSIONS: Past users of older, higher dose oral contraceptives can be reassured that the small increased risk of serious disease seen during current use does not persist after stopping, and that latent effects do not appear later in life. Currently available oral contraceptives, containing less than 50 micrograms of oestrogen accompanied by the progestogen, levonorgestrel, or norethisterone acetate, do not appear to be associated with an increased net risk of serious disease.

Several studies have suggested that prolonged use of oral contraceptives may increase a woman's risk of developing malignant melanoma. In the Royal College of General Practitioners' Oral Contraception Study, 31 cases of malignant melanoma (code 172--International Classification of Diseases, 8th Revision) have been reported among ever-users and 27 cases among never-users. The risk ratio (RR) (indirectly standardised for age, parity, social class and smoking) was 0.92 (95% confidence interval (CI) 0.55-1.54). There was no significant trend with duration of oral contraceptive use, although those women who had used the pill for at least 10 years had an elevated RR of 1.77 (95% CI 0.80-3.90). The Oxford/Family Planning Association Study has recorded 15 cases among ever-users and 17 cases among never-users; the standardised risk ratio was 0.85 (95% CI 0.42-1.70). None of the rates observed in any duration of use category was materially different from those observed in never-users. The results available so far from the two studies suggest that oral contraceptive use is probably not associated with an increased risk of malignant melanoma.

A case-control study of the use of oral contraceptives was conducted among women certified as having died from cancer of the liver in the period 1979-82 and in the age range 20-44 years. An age matched group of women who died from other causes, not related to use of oral contraceptives, in the same period were used as controls. Information about use of oral contraceptives was obtained from the general practitioners' notes for both cases and controls. Information was obtained for 30 women with histologically confirmed liver cancer, 19 with hepatocellular carcinoma and 11 with cholangiocarcinoma, and for 147 controls. The results were analysed after adjusting for age at diagnosis and year of birth and showed that use of oral contraceptives was associated with a significantly (p less than 0.05) raised relative risk for hepatocellular carcinoma of 3.8 (95% confidence interval 1.0 to 14.6) and use for eight years or more was associated with a significantly (p less than 0.01) increased relative risk of 20.1 (2.3 to 175.7). There were no apparent increases in risk for cholangiocarcinoma. Despite the small number of cases in this study and the methodological problems in assessing use of oral contraceptives from general practitioners' notes, the results were consistent with other similar studies. Although in the United Kingdom primary liver cancer remains an exceptionally rare disease, especially in young women, further research on the role of oral contraceptives is needed in those countries where it is a much more common disease.

From data available at April 1987 it was found that the standardised risk ratio for rheumatoid arthritis between current users of oral contraceptives and never users was 0.82 (95% confidence interval 0.59 to 1.15); the ratio between former users and never users was 0.94 (95% confidence interval 0.72 to 1.22). Important secular trends have occurred within our study population. The incidence of rheumatoid arthritis among former and never users has declined over the past two decades. Current users have not experienced this temporal trend, and the ratio between current and never users has, therefore, approached unity. These secular changes may explain why some studies have found that oral contraceptives have a protective effect, while others have been unable to show such an effect.

Objective: To explore the usefulness of epidemiological data to guide clinical practice by seeking an answer to the question “What is the risk of cardiovascular disease among users of currently available, low dose, combined oral contraceptives who are aged less than 35 years, do not smoke, and do not have a medical condition known to increase the risk of vascular disease?”

Design: Review of all relevant published studies identified from the library of references held by Royal College of General Practitioners’ Manchester Research Unit, checking of reference lists of identified studies, and Medline search.

Main outcome measures: Identification of methodologically sound studies able to address the specific clinical question.

Results: Our literature search identified 74 papers about the relation between current use of combined oral contraceptives and cardiovascular disease: 23 papers reporting risk of venous thromboembolism, 22 on ischaemic stroke, 13 on haemorrhagic stroke or subarachnoid haemorrhage, 13 on all stroke, and 33 on myocardial infarction. Only five papers provided information that directly addressed our clinical question; all related to the risk of venous thromboembolism. Fourteen of the discarded papers probably had the potential to answer our clinical question.

Conclusions: Much of the epidemiological data about the risk of cardiovascular disease in users of combined oral contraceptives is not useful to clinicians. Some of the discarded data could be made more useful to clinicians by reanalysis. This situation is unlikely to be unique to use of contraceptives.

Key messages Epidemiological studies investigate overall, average effects within populations, but clinicians need information about specific risks and benefits faced by the individual patients consulting them We explored the clinical usefulness of epidemiological data in defining the risk of cardiovascular disease associated with currently available low dose combined oral contraceptives for young, healthy women who do not smoke Our literature search identified 74 papers about the subject, but only five provided information that directly addressed our clinical question Fourteen other studies probably had the potential to answer our question if their data were reanalysed Clinicians need to be cautious when extrapolating results from epidemiological studies to guide their clinical practice

Objective

To compare the risk of idiopathic venous thromboembolism among women taking third generation oral contraceptives (with gestodene or desogestrel) with that among women taking oral contraceptives with levonorgestrel.

Design

Cohort and case-control analyses derived from the General Practice Research Database.

Setting

UK general practices, January 1993 to December 1999.

Participants

Women aged 15-39 taking third generation oral contraceptives or oral contraceptives with levonorgestrel.

Main outcome measures

Relative incidence (cohort study) and odds ratios (case-control study) as measures of the relative risk of venous thromboembolism.

Results

The adjusted estimates of relative risk for venous thromboembolism associated with third generation oral contraceptives compared with oral contraceptives with levonorgestrel was 1.9 (95% confidence interval 1.3 to 2.8) in the cohort analysis and 2.3 (1.3 to 3.9) in the case-control study. The estimates for the two types of oral contraceptives were similar before and after the warning issued by the Committee on Safety of Medicines in October 1995. A shift away from the use of third generation oral contraceptives after the scare was more pronounced among younger women (who have a lower risk of venous thromboembolism) than among older women. Fewer cases of venous thromboembolism occurred in 1996 and later than would have been expected if the use of oral contraceptives had remained unchanged.

Conclusions

These findings are consistent with previously reported studies, which found that compared with oral contraceptives with levonorgestrel, third generation oral contraceptives are associated with around twice the risk of venous thromboembolism.

An analysis of the occurrence of breast cancer in this long-term prospective cohort study shows a significant relative risk (RR) in women who have ever used oral contraceptives (OC) of 3.33 in women age 30 to 34 years at diagnosis and an RR of 5.88 (P = 0.0011) in women who were parity 1 at the time of diagnosis. In women below the age of 35 years the RR of 2.38 was not significant. There was no increased risk in women over the age of 35 years. A significant trend relating to duration of use was demonstrable in women who were parity 1 in the analysis of both current and ever-users. An analysis by time since stopping OC use revealed a significant trend in all ever-users, but the trends were much steeper in women of parity 1 or aged 30 to 34 years at diagnosis. There was no evidence that the increased rates in OC users were related to the oestrogen or progestogen dose. The 5 year survival rate in users diagnosed under the age of 35 years was significantly poorer than in comparable non-users. It is possible that the increased rates in younger OC users might be due to an accelerated presentation of breast cancer in those women who would otherwise have been diagnosed at a later time. The non-significant excess risk in users under 35 years of age was approximately 1 in 7,000 users per year. The unresolved discrepancies between the results of the published studies make it impossible at the present time to decide whether or not OC use is associated with an increased risk of breast cancer.

Background

In Curaçao is a high incidence of unintended pregnancies and induced abortions. Most of the induced abortions in Curaçao are on request of the woman and performed by general practitioners. In Curaçao, induced abortion is strictly prohibited, but since 1999 there has been a policy of connivance. We present data on the relevance of economic and socio-cultural factors for the high abortion-rates and the ineffective use of contraception.

Methods

Structured interviews to investigate knowledge and attitudes toward sexuality, contraception and abortion and reasons for ineffective use of contraceptives among women, visiting general practitioners.

Results

Of 158 women, 146 (92%) participated and 82% reported that their education on sexuality and about contraception was of good quality. However 'knowledge of reliable contraceptive methods' appeared to be - in almost 50% of the cases - false information, misjudgements or erroneous views on the chance of getting pregnant using coitus interruptus and about the reliability and health effects of oral contraceptive pills. Almost half of the interviewed women had incorrect or no knowledge about reliability of condom use and IUD. 42% of the respondents risked by their behavior an unplanned pregnancy. Most respondents considered abortion as an emergency procedure, not as contraception. Almost two third experienced emotional, physical or social problems after the abortion.

Conclusions

Respondents had a negative attitude toward reliable contraceptives due to socio-cultural determined ideas about health consequences and limited sexual education. Main economic factors were costs of contraceptive methods, because most health insurances in Curaçao do not cover contraceptives. To improve the effective use of reliable contraceptives, more adequate information should be given, targeting the wrong beliefs and false information. The government should encourage health insurance companies to reimburse contraceptives. Furthermore, improvement of counseling during the abortion procedure is important.

Background

Oral contraceptive formulations have changed over time, making it relevant to assess the effect of more recent formulations on breast cancer risk. In addition, some studies have found stronger positive associations of oral contraceptive use with estrogen receptor negative (ER−) than with ER positive (ER+) breast cancer. We carried out the first assessment of the effect of oral contraceptive use on the incidence of breast cancer classified by receptor status among African-American women, a group disproportionately affected by ER− cancer.

Methods

We followed 53,848 Black Women's Health Study participants from 1995–2007 through biennial health questionnaires, on which participants reported information about incident breast cancer, oral contraceptive use, and breast cancer risk factors. Pathology information was obtained on receptor status for 789 incident cases. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were derived from Cox regression models with control for confounding factors.

Results

Ever use of oral contraceptives was more strongly associated with ER−PR− breast cancer (279 cases, IRR=1.65, 95% CI 1.19–2.30) than with ER+PR+ cancer (386 cases, IRR=1.11, 95% CI 0.86–1.42). The risk of ER−PR− breast cancer increased with increasing duration of use among recent users.

Conclusions

These results indicate that oral contraceptive formulations used in recent decades increase breast cancer risk in African-American women, with a greater effect for ER− than ER+ cancer.

Impact

Mechanisms to explain an adverse influence of oral contraceptive use on ER− breast cancer need to be elucidated.

In a case-control study, we investigated 169 women aged 15-49 years with malignant melanoma notified to the Oxford and South Western cancer registries during the years 1971-1976, together with 507 matched controls. Data about medical, reproductive, drug and smoking histories were obtained both by reviewing general practitioner (GP) records and from the women themselves by postal questionnaires. There was no significant evidence of any overall increase in the risk of melanoma in oral contraceptive (OC) users (data from GP records-ever use vs never use, relative risk (RR) 1.34, 95% confidence limits 0.92-1.96; corresponding data from postal questionnaires-RR 1.13, limits 0.73-1.75). However, although not significant, the risk estimated from data in the postal questionnaires was higher in women who had used OCs for 5 years or more (use greater than or equal to 5 years vs never use, RR 1.57, limits 0.83-3.03). Previously demonstrated risk factors for melanoma, such as fair skin, blond or red hair and Celtic origin were found to be commoner in the cases than in the controls. Data from the Oxford/Family Planning Association contraceptive study were also examined. Unexpectedly there was a strong suggestion of a negative association between OC use and melanoma risk, but the analysis was based on only 12 women with the disease.

Data on 2,754 cases and 18,565 controls from a multinational hospital-based, case-control study were analysed to determine whether observed associations between combined oral contraceptives and breast cancer are similar for oral contraceptives with varying types and doses of oestrogens and progestins. After stratifying on duration of use, risk was found to be increased in current and recent users, and to decline with time since last use. These associations, of similar strength, were observed for users of products that contain mestranol and ethinyl estradiol, for women who used preparations with progestins derived from 19-nortestosterone and 17-alpha-hydroxyprogesterone, and for those who took preparations with relatively higher and lower doses of oestrogen. When products with equal doses of the same oestrogen or progestin and varying doses of the other hormonal constituent were considered, slightly higher relative risks per year of use were estimated for users of products with relatively higher than lower doses of either the constituent oestrogen or progestin, but the differences in relative risk could readily have occurred by chance. This study provides no evidence that risk of breast cancer in users of oral contraceptives varies by the type of oestrogen or progestin consumed.

There is increasing concern that contraceptive pill usage may increase the risk of hepatocellular carcinoma. As primary malignant liver cancer is very rare in this country, any effect due to oral contraceptives should be apparent in national mortality statistics. An analysis of mortality rates over the last 24 years shows a small but consistent increase for young women starting to occur during the end of the last decade. However no such trend is apparent in data from other countries where pill usage is comparable to that in the U.K. Overall liver cancer remains an extremely uncommon cause of death in developed countries, but it will be particularly important to monitor trends in this disease in the future.

Objectives

Several new methods are available, but we know little about successful integration of contraceptive technologies into services. We investigated provider factors associated with the initiation of new hormonal methods among women at high-risk of unintended pregnancy.

Methods

This cohort study enrolled 1,387 women aged 15–24 starting hormonal contraception (vaginal ring, transdermal patch, oral contraceptive, or injectable) at four family planning clinics in low-income communities. We measured provider factors associated with method choice, using multinomial logistic regression.

Results

Ring and patch initiators were more likely than women starting oral contraceptives to report that they chose their method due to provider counseling (p<0.001). Contraceptive knowledge in general was low, but initiation of a new method, the ring, was associated with higher knowledge about all methods after seeing the provider (p<0.001). Method initiated varied with provider site (p<0.001). These associations remained significant, controlling for demographics and factors describing the provider-patient relationship, including trust in provider and continuity of care.

Conclusion

Women’s reports of provider counseling and of their own contraceptive knowledge after the visit was significantly associated with hormonal method initiated.

Practice Implications

More extensive counseling and patient education should be expected for successful integration of new hormonal methods into clinical practice.

The higher incidence of breast cancer among African-American women younger than 50 as compared to white women points to the need to examine exposures that are common among younger women, including exposure to oral contraceptives (OC). We examined patterns of OC use and their associations with breast cancer in a population-based, case-control study conducted in North Carolina between 1993 and 1996. The study population was comprised of 858 cases and 789 controls, of whom 40% were African-American women. There was little evidence that breast cancer was associated with OC use among older women (age >50) of either race, most of whom discontinued use in the distant past. Among younger women, there was a modest, but nonsignificant, increase in risk associated with ever use of OCs for both African-American and white women. There was a trend of increasing risks with more recent use among African-American women, whereas no such trend was apparent for white women. Overall, we found more substantial age differences than race differences in patterns of OC use and the risk of breast cancer associated with their use. The similarity of the associations between African-American and white women suggest that racial differences in breast cancer incidence are not likely to be attributable to OC use.