Background: This analysis provides the final results on cancer incidence in relation to oral contraceptive (OC) use from the Oxford Family Planning Association (Oxford-FPA) contraceptive study, which closed at the end of 2010. An additional 6 years of observation have been added since our last report and there has been an increase in the numbers of cancers of over 50% at seven of the sites considered.Study Design: The Oxford-FPA study includes 17032 women aged 25-39 years recruited from 1968 to 1974 at contraceptive clinics in England and Scotland. These women were using OCs, a diaphragm or an intrauterine device. Information about cancer incidence among them has been collected from recruitment until closure of the study.Results: OC use was not related to nonreproductive cancer. Breast cancer findings (1087 cases) were entirely negative; the rate ratio (RR) comparing ever users of OCs with never users was 1.0 [95% confidence interval (CI): 0.9-1.1]. Only two cases of cervical cancer have been added since our last report (total: 61 cases); the RR comparing ever use with never use is now 3.4 (95% CI: 1.6-8.9). The risk of this disease increases sharply with duration of OC use and declines steadily with interval since last OC use. OC use protects against both uterine body cancer (124 cases) and ovarian cancer (143 cases). The RRs comparing ever use with never use were 0.5 (95% CI: 0.3-0.7) and 0.5 (95% CI: 0.4-0.7), respectively. Protection against both these cancers increased with duration of OC use and waned with interval since last use, but an effect was still present 28 or more years after discontinuation.Conclusions: In our study, OC use had no effect on nonreproductive cancers or on breast cancer. The risk of cervical cancer was increased and that of uterine body cancer and ovarian cancer was decreased by OC use. All these effects increased with duration of use and declined with interval since last use. The beneficial effects of OC use on cancer outweighed the adverse effects. These findings should reassure older women who used OCs in the past. (C) 2013 Elsevier Inc. All rights reserved.

At recruitment to the Oxford-Family Planning Association (Oxford-FPA) study, oral contraceptive (OC) users were less likely to give a history of hospital treatment for varicose veins (VVs) than users of other contraceptive methods. Adjusted for age and parity, 1.6% of OC users gave such a history compared with 2.3% of diaphragm users and 3.9% of intrauterine device (IUD) users. We have examined the occurrence of VVs during follow-up in relation to various factors, including OC use. For comparison, we also analysed the data on haemorrhoids, a condition responsible for hospital referral with similar frequency at recruitment (about 0.4%) among the three contraceptive groups. The Oxford-FPA study includes 17 032 women who, when recruited between 1968 and 1974, …

OBJECTIVES:To analyse cervical screening coverage data by age over time in a number of developed countries throughout the world, with specific emphasis on trends for younger women and on age differentials between younger and older women.METHODS:Routinely collected cervical screening statistics and survey data were collected on the proportion of women who have undergone cervical screening with cytology in seven countries in the period 1995 to 2005.RESULTS:Data for the 25-29 age group were examined. Coverage fell in most countries, in three by more than 5 percentage points. In two countries while overall coverage rose in the period, the rise was not as steep in the youngest group of women. Data for each available 5-year age group for the different countries shows a similar gradient in most, regardless of the absolute level of coverage. Although the trend is not uniform in every country, it appears that generally the gap between coverage of younger women and coverage of older women increased, sometimes dramatically, between the mid-1990s and the mid-2000s.CONCLUSIONS:There is a general trend in developed countries towards lower coverage in young women (25-29 years old). No common underlying cause has been clearly identified and there is a need for further studies to investigate the possible reasons for this phenomenon.

Background: This analysis updates mortality in the Oxford-Family Planning Association (Oxford-FPA) contraceptive study, with emphasis on oral contraceptive (OC) use.Study design: The Oxford-FPA study includes 17,032 women recruited from 1968-1974 at contraceptive clinics, aged 25-39 years, using OCs a diaphragm or an intrauterine device. Follow-up has been to March 2009; by then, 1715 women had died.Results: The rate ratio (RR) for overall mortality was 0.87 (CI 0.79-0.96), comparing ever-users of OCs with never-users. The RR for fatal cervical cancer was increased (7.3), but the CIs were very wide (1.2-305). There was no association between ever-use of OCs and mortality from breast cancer (RR 1.0, CI 0.8-1.2), nor was fatal breast cancer related to duration of OC use. OC use strongly protected against death from other uterine cancer and ovarian cancer; RRs for ever-use of OCs were 0.3 (CI 0.1-0.8) and 0.4 (CI 0.3-0.6), respectively. Protection increased with duration of OC use and persisted more than 20 years after cessation. Circulatory disease mortality was not increased, the RR for ever-use of OCs being 0.9 (CI 0.7-1.1). The overall mortality RR for all women smoking 15+ cigarettes daily was 2.25 (CI 1.99-2.53) and, for all women with a body mass index of 28+ kg/m(2), was 1.33 (CI 1.07-1.64).Conclusions: Long-term follow-up strongly suggests that OC use slightly reduces all cause mortality. (C) 2010 Elsevier Inc. All rights reserved.

BACKGROUND:Benign breast disease (BBD) increases the risk of breast cancer, but details of the relationship would benefit from further study in the UK.METHODS:Analysis of linked statistical abstracts of hospital data, including a cohort of 20 976 women with BBD in an Oxford data set and 89 268 such women in an English national data set.RESULTS:Rate ratios (RRs) for breast cancer, comparing BBD and comparison cohorts in these two data sets, were 2.3 (95% CI: 2.2-2.5) and 3.2 (3.0-3.3), respectively. RRs rose with increasing age at BBD diagnosis and remained elevated for at least 20 years after diagnosis. RRs were particularly high for a relatively small number of cancers occurring in the first few months after BBD diagnosis.CONCLUSIONS:Our findings accord well with those in other large studies, mostly done in the USA, in showing a sustained long-term cancer risk after BBD. They also demonstrate that known long-term risks of disease can be reliably identified from linked routine administrative hospital statistics. Most other studies omit cancers in the first few months after BBD. Such cases-presumably either misdiagnosed or miscoded-merit further study to determine whether in fact they include diagnoses of cancer that were initially missed.

Background The Oxford-Family Planning Association (Oxford-FPA) contraceptive study has provided information on many serious diseases of the female reproductive tract. No information has been published about a number of common minor conditions. This report fills the gap with regard to uterine polyp, cervicitis, cervical erosion, and vaginitis and vulvitis.Methods The Oxford-FPA study includes 17 032 married women recruited at ages 25-39 years between 1968 and 1974 from clinics in England and Scotland. These women were followed up until mid-1994. Information collected during follow-up included details of contraceptive use, cervical smears taken at the clinic, pregnancies and hospital referrals.Results Oral contraceptive (OC) use was associated with a reduction in first hospital referral for uterine polyp and for vaginitis and vulvitis, which became more marked with increasing duration of use. There was a slightly increased rate of hospital referral for cervicitis in OC users. Referral for cervical erosion was markedly increased in current and recent OC users (rate ratio 2.1, 95% confidence interval 1.8-2.4). This increase in risk steadily declined after OC use was discontinued. First hospital referral for both uterine polyp and cervical erosion showed a highly significant negative association with numbers of cigarettes smoked per day. The explanation for these observations is unknown.Conclusions It should be remembered that the OCs studied were mainly those used in the 1970s and 1980s and mostly contained 50 mu g estrogen. On balance, the overall effect of OC use on the conditions considered was neutral or beneficial. The apparent protective effect of cigarette smoking against uterine polyp and cervical erosion, even if valid, counts as nothing against the overwhelming adverse effects of smoking on health.

Placental lead levels were studied in a series of Birmingham births classified by stillbirth, neonatal death, or survival beyond one week. There was an appreciable range of lead levels even in normal births (0.15-3.56 microgram/g) but nevertheless average results showed a pronounced excess of lead in those who failed to survive both birth and the neonatal period. There was no association of placental lead with impaired birthweight among survivors but, in common with other authors, we noted a seasonal variation. The placentae from Indian women had similar lead levels to those from European women and lower values were found in the normal sibs of stillbirths and neonatal deaths. The possibility is discussed that under conditions of impaired fetal health in late pregnancy the placenta may concentrate lead.

Background Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We aimed to assess these effects.Methods Individual data for 23 257 women with ovarian cancer (cases) and 87 303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use was estimated, stratifying by study, age, parity, and hysterectomy.Findings Overall 7308 (31%) cases and 32 717 (37%) controls had ever used oral contraceptives, for average durations among users of 4 . 4 and 5 . 0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average of 56 years. The longer that women had used oral contraceptives, the greater the reduction in ovarian cancer risk (p<0. 0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased but became somewhat attenuated over time the proportional risk reductions per 5 years of use were 29% (95% CI 23-34%) for use that had ceased less than 10 years previously, 19% (14-24%) for use that had ceased 10-19 years previously, and 15% (9-21%) for use that had ceased 20-29 years previously. Use during the 1960s, 1970s, and 1980s was associated with similar proportional risk reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The incidence of mucinous tumours (12% of the total) seemed little affected by oral contraceptives, but otherwise the proportional risk reduction did not vary much between different histological types. In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1 . 2 to 0 . 8 per 100 users and mortality from 0 . 7 to 0 . 5 per 100; for every 5000 woman-years of use, about two ovarian cancers and one death from the disease before age 75 are prevented.Interpretation Use of oral contraceptives confers long-term protection against ovarian cancer. These findings suggest that oral contraceptives have already prevented some 200000 ovarian cancers and 100000 deaths from the disease, and that over the next few decades the number of cancers prevented will rise to at least 30 000 per year.

Additional material for this article is available from the James hind Library website [www.jameslindlibrary.org], where it was previously published.

Active smoking has little or no effect on breast cancer risk but some investigators have suggested that passive smoking and its interaction with active smoking may be associated with an increased risk. In a population based case–control study of breast cancer in women aged 36–45 years at diagnosis, information on active smoking, passive smoking in the home, and other factors, was collected at interview from 639 cases and 640 controls. Women were categorised jointly by their active and passive smoking exposure. Among never smoking controls, women who also reported no passive smoking exposure were significantly more likely to be nulliparous and to be recent users of oral contraceptives. Among those never exposed to passive smoking, there was no significant association between active smoking and breast cancer, relative risk (RR) of 1.12 (95% confidence interval (CI) 0.72–1.73) for past smokers and RR of 1.19 (95% CI 0.72–1.95) for current smokers, nor was there an association with age started, duration or intensity of active smoking. Compared with women who were never active nor passive smokers, there was no significant association between passive smoking in the home and breast cancer risk in never smokers, RR of 0.89 (95% CI 0.64–1.25), in past smokers, RR of 1.09 (95% CI 0.75–1.56), or in current smokers, RR of 0.93 (95% CI 0.67–1.30). There was no trend with increasing duration of passive smoking and there was no heterogeneity among any of the subgroups examined. In this study, there was no evidence of an association between either active smoking or passive smoking in the home and risk of breast cancer.

Active smoking has little or no effect on breast cancer risk but some investigators have suggested that passive smoking and its interaction with active smoking may be associated with an increased risk. In a population based case - control study of breast cancer in women aged 36 - 45 years at diagnosis, information on active smoking, passive smoking in the home, and other factors, was collected at interview from 639 cases and 640 controls. Women were categorised jointly by their active and passive smoking exposure. Among never smoking controls, women who also reported no passive smoking exposure were significantly more likely to be nulliparous and to be recent users of oral contraceptives. Among those never exposed to passive smoking, there was no significant association between active smoking and breast cancer, relative risk ( RR) of 1.12 ( 95% confidence interval ( CI) 0.72 - 1.73) for past smokers and RR of 1.19 ( 95% CI 0.72 - 1.95) for current smokers, nor was there an association with age started, duration or intensity of active smoking. Compared with women who were never active nor passive smokers, there was no significant association between passive smoking in the home and breast cancer risk in never smokers, RR of 0.89 ( 95% CI 0.64 - 1.25), in past smokers, RR of 1.09 ( 95% CI 0.75 - 1.56), or in current smokers, RR of 0.93 ( 95% CI 0.67 - 1.30). There was no trend with increasing duration of passive smoking and there was no heterogeneity among any of the subgroups examined. In this study, there was no evidence of an association between either active smoking or passive smoking in the home and risk of breast cancer.

Background: This report is an update of findings, first reported in 1981, on the relationship between oral contraceptives (OCs) and benign breast disease with special reference to OCs containing <50 mcg estrogen.Study Design: The Oxford-Family Planning Association study includes 17,032 women using different methods of contraception recruited at 17 family planning clinics between 1968 and 1974. These women were subsequently followed up until mid-1994. Among other items, information about contraceptive method changes and morbidity as measured by hospital referrals was collected during follow-up.Results: The findings in the present analysis were broadly similar to those reported in 1981, but based on much larger numbers of cases [fibroadenoma (FA), 185 cases; chronic cystic disease (CCD), 1361 cases; breast lump with no specific diagnosis (BL), 650 cases]. Hospital referral rates for FA and CCD (but not BL) declined with increasing duration of OC use, with the effect being strongest among recent users. The apparent protective effect was present for women using OCs containing >50 mcg, 50 mcg and <50 mcg estrogen but not for progestogenonly OCs.Conclusion: Low-dose combined OCs containing <50 mcg estrogen appear to reduce the risk of hospitalization for FA and CCD as well as older preparations containing higher doses of estrogen. (c) 2007 Elsevier Inc. All rights reserved.

Oral contraceptives and diabetes mellitus: an update There has long been interest in the possible relationship between oral contraceptive (OC) use and diabetes mellitus. In 1991, we reported our findings (in this Journal) on 45 women who had been referred to hospital for diabetes during follow-up in the Oxford-Family Planning Association (Oxford-FPA) contraceptive study. No association was found with OC use.1 We nonetheless thought it would be of interest to comment briefly on the findings for this disease up to the time that individual follow-up of the study participants ceased in July 1994 (follow-up of cancer registrations and death notifications is still continuing). The Oxford-FPA study methods have been described in detail elsewhere.2 In brief, the study includes 171032 white women who, when recruited between 1968 and 1974, were married and aged between 25 and 39 years. At entry, 56% were using OCs, 25% a diaphragm and 19% an intrauterine device. These women (save for certain subgroups – see Vessey and Painter3) were followed up annually and information was collected about changes in contraceptive methods, pregnancies and their outcome, hospital referrals and deaths. Women who at entry to the study reported that they were suffering from diabetes were excluded from the present analyses. There were 81 cases remaining. Only the first hospital referral (inpatient or outpatient) was taken into account in the analyses. As expected, hospital referral was strongly positively related to age and body mass index (BMI). In addition, referral was three times as common in women of lower social class (IV–VI) as in women of upper social class (I–II), a difference only partly explained by BMI. Analyses of hospital referral rates in relation to OC use were therefore adjusted for age, BMI and social class. Our first analysis compared women ever using OCs with those never doing so. The rate ratio was 0.8 with a 95% confidence interval (CI) ranging from 0.5 to 1.3. Rate ratios for hospital referral in relation to total duration of OC use were as follows (95% CIs are given in parentheses): never used, 1.0 (reference category); 1–48 months, 0.9 (0.3–2.1); 49–96 months, 0.7 (0.3–1.7); 97–144 months, 0.9 (0.5–1.7); 145 months or more, 0.6 (0.2–1.6). Corresponding rate ratios in relation to interval since last use of OCs were as follows: never used, 1.0 (reference category); current–48 months, 0.7 (0.3–1.4); 49–96 months, 0.7 (0.3–1.7); 97–144 months, 0.6 (0.2–1.5); 145 months or more, 1.5 (0.7–2.8). The data were too few to enable analyses to be done by type of OC, but it should be noted that preparations containing 50 μg oestrogen made up 67% of OC exposure. OCs containing a greater amount of oestrogen provided only 2% of exposure. We recognise the shortcomings of our data, which include the small number of affected women and the associated fact that only those referred to hospital with diabetes were identified. Nonetheless we believe that our case finding has been unbiased with respect to OC use. Furthermore, as we have pointed out previously,1 if such a bias existed it might be expected to lead to hospital referral of more OC users than nonusers. In conclusion, the final results of the Oxford-FPA study with respect to diabetes mellitus offer further support to the view that OC use does not increase the risk of clinical diabetes mellitus, a finding in keeping with most other studies.4–6 Martin Vessey, FRCP, FRS Emeritus Professor of Public Health, Unit of Health Care Epidemiology, University of Oxford Old Road Campus, Headington, Oxford OX3 7LF, UK. E-mail: martin.vessey@dphpc.ox.ac.uk

Pregnancy outcome and characteristics of women who conceive following subfertility treatment remains a subject of great interest. We analyzed these variables among 199 women who delivered a registerable twin birth compared with 1773 women who delivered a naturally conceived twin birth in a population-based obstetric cohort drawn from around Oxford, England. Treatment was restricted to conceptions involving simple ovulation induction only. Treated mothers were of significantly higher social class and older, more likely to deliver girls and to be delivered by cesarean section, and significantly less likely to be smokers at the time of antenatal booking and to have delivered previous pregnancies. Pregnancy outcome was similar between the two groups for most measures, with the exception of birthweight which was lower in treated twins, though not significantly so. Overall the results are reassuring with respect to outcome in twin pregnancies following simple ovulation induction.

We examined cancer incidence in relation to oral contraceptive (OC) use in the Oxford Family Planning Association contraceptive study. The study includes 17032 women, recruited at family planning clinics at ages 25–39 years between 1968 and 1974, who were using OCs, a diaphragm, or an intrauterine device. Follow-up data were available until 2004. OC use was not significantly related to nonreproductive cancer. Breast cancer findings (844 cases) likewise were very reassuring (rate ratio (RR) comparing women ever using OCs with those never doing so 1.0, 95% confidence interval (CI) 0.8–1.1). There was a strong positive relationship between cervical cancer incidence (59 cases) and duration of OC use (RR comparing users for 97+ months with nonusers 6.1, 95%CI, 2.5–17.9). Uterine body cancer (77 cases) and ovarian cancer (106 cases) showed strong negative associations with duration of OC use: RRs for 97+ months of use were 0.1 (95%CI, 0.0–0.4) and 0.3 (95%CI, 0.1–0.5) respectively. This apparent protective effect for both cancers persisted more than 20 years after stopping OCs. Combining data for cancers of the cervix, uterine body and ovary, the age adjusted RR for women ever using OCs compared with those never doing so was 0.7 (95%CI, 0.5–0.8). Beneficial effects of OCs on the gynaecological cancers thus outweighed adverse effects.

We examined the relationship between body fatness, sports participation and breast cancer risk in 1560 premenopausal cases and 1548 controls, from three related population-based case–control studies in the UK. Half of the women with breast cancer were aged less than 36 years at diagnosis. Women who perceived themselves as plump at age 10 years had a relative risk of 0.83 (95% confidence interval 0.69–0.99, P =0.03) as compared with those who perceived themselves as thin. Self-reported obesity compared with leanness at diagnosis was associated with a relative risk of 0.78 (95% confidence interval 0.56–1.06, P =0.11). Women who reported having been plump at age 10 years and overweight or obese at diagnosis had a relative risk of 0.75 (95% confidence interval 0.56–1.01, P =0.06) as compared with those who reported being thin at age 10 years and at diagnosis. Findings for three related measures of body fatness suggested that obesity is associated with a reduced risk of premenopausal breast cancer. There was no association between sports participation and breast cancer risk in these premenopausal women. The relative risk for spending an average of more than 1 h per week in sports compared with less from ages 12 to 30 years was 1.00 (95% CI 0.86–1.16, P =0.98).

Background: The long term safety of potent gastric acid suppressive therapy has yet to be established.Method: General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993 - 1995. Death rates were compared with general population rates.Results: Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34 - 1.55); p< 0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 ( 95% CI 1.58 - 2.08); p< 0.0001), circulatory diseases (1.27 (95% CI 1.13 - 1.43); p< 0.0001), and respiratory diseases (1.37 ( 95% CI 1.12 - 1.64); p< 0.001). Increased mortality ascribed to digestive diseases (2.56 ( 95% CI 1.87 - 3.43); p< 0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 ( 95% CI 2.60 - 6.04); p< 0.0001), colon and rectum (1.40 ( 95% CI 0.84 - 2.18); p = 0.075), and trachea, bronchus, and lung ( 1.64 ( 95% CI 1.19 - 2.19); p< 0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 ( 95% CI 5.20 - 10.09) ( p< 0.0001) in year 1; 2.88 ( 95% CI 1.62 - 4.79) ( p< 0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett's disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 ( 95% CI 2.17 - 4.80)). Six deaths occurred in patients with hiatal hernia or reflux only ( O/E 1.02 ( 95% CI 0.37 - 2.22)) and five in patients without oesophageal disease (O/E 0.77 ( 95% CI 0.25 - 1.80)). No relationships were detected with numbers of omeprazole scripts received.Conclusions: Increases in mortality associated with treatment are due to pre-existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration.

We believe that Vessey and colleagues underestimated mortality associated with hormone use and that the comparison in their study between smoking mortality and hormonerelated mortality is misleading for two reasons. (excerpt)