Maternal gestational weight gain and offspring's risk of cardiovascular disease and mortality.

OBJECTIVE: To examine the effect of maternal gestational weight gain (GWG) on adult offspring mortality, cardiovascular morbidity and cerebrovascular morbidity. METHODS: The Aberdeen Children of the Nineteen Fifties (ACONF) is a population-based cohort of adults born in Aberdeen, Scotland between 1950 and 1956. GWG of the mothers of cohort members was extracted from original birth records and linked to the data on offspring morbidity and mortality up to 2011 obtained from Scottish national records. HRs for cardiovascular events and mortality in offspring according to maternal weight gain in pregnancy were estimated adjusting for maternal and offspring confounders using a restricted cubic spline model. RESULTS: After exclusions, 3781 members of the original ACONF cohort were analysed. Of these, 103 (2.7%) had died, 169 (4.5%) had suffered at least one cardiovascular event and 73 (1.9%) had had a hospital admission for cerebrovascular disease. Maternal weight gain of 1 kg/week or more was associated with increased risk of cerebrovascular event in the offspring (adjusted HR 2.70 (95% CI 1.19 to 6.12)). There was no association seen between GWG and offspring's all-cause mortality or cardiovascular event. Adult offspring characteristics (smoking, body mass index (BMI) and diabetes) were strongly associated with each outcome. CONCLUSIONS: Maternal GWG above 0.9 kg/week may increase the risk of cerebrovascular disease in the adult offspring, but not all-cause mortality or cardiovascular disease. Health and lifestyle factors such as smoking, BMI and diabetes in the adult offspring had a stronger influence than maternal and birth characteristics on their mortality and morbidity.

Factors associated with reporting classic menopausal symptoms differ.

OBJECTIVES: To investigate how symptoms experienced in midlife cluster and to identify factors independently associated with hot flushes, night sweats, and vaginal dryness. METHODS: A questionnaire was sent to 8206 women aged 45-54 years, recruited from family practices in north-east Scotland, UK. Using data collected about 23 symptoms, we conducted factor analysis for premenopausal, perimenopausal, postmenopausal and surgically menopausal women. Forward stepwise logistic regression was used to identify sociodemographic, lifestyle and psychological variables independently associated with the classic menopausal symptoms. RESULTS: Overall, 4407 women responded. Hot flushes were experienced by 46.7% (95% confidence interval (CI) 45.2-48.2) of women, night sweats by 46.4% (95% CI 44.9-47.9) and vaginal dryness by 28.2% (95% CI 26.9-29.6). Seven factors including 20 symptoms emerged from factor analysis. Hot flushes were associated with: being perimenopausal or postmenopausal; low education; obesity; low social support; reporting night sweats, musculoskeletal, bloating, menstrual and sexual symptoms; using complementary alternative medicines, lifestyle (e.g. exercising) or psychological management strategies (e.g. talking to family or friends) for menopausal symptoms. Night sweats were associated with: lower body weight; smoking; possible depression; reporting sleep difficulties, hot flushes and sexual symptoms; using lifestyle strategies for menopausal symptoms. Vaginal dryness was associated with: being postmenopausal; high education; high social support; below average physical health, reporting hot flushes, somatic symptoms and decreased sexual interest; using psychological or lifestyle strategies for menopausal symptoms. CONCLUSION: It is important to investigate each classic menopausal symptom separately. Combining menopausal symptoms into categories such as vasomotor symptoms may lead to inaccurate conclusions about variables associated with these symptoms.

Hypertensive disorders of pregnancy and future health and mortality: A record linkage study.

The objective of this register-based cohort study was to examine the relationship between hypertensive disorders of pregnancy and future hospital discharges from specified causes including cardiovascular disease, incident cancer registrations and mortality. From the Aberdeen Maternity and Neonatal Databank we identified 34,854 women who were born on or before 31st December 1967 and who had (i) preeclampsia/eclampsia, (ii) gestational hypertension or (iii) normal blood pressure in their first pregnancy. Hospital discharges from selected causes including cardiovascular disease, cancer registrations and deaths in these women were identified from the Scottish Morbidity Records. There were 2026 women who had preeclampsia, 8891 who had gestational hypertension and 23,937 who were normotensive during their first pregnancy. Compared to normotensive women, women with preeclampsia had a higher mortality from ischaemic heart disease (adj. IRR 1.38, 95% CI 1.03, 1.84) and circulatory disease (adj. IRR 1.30, 95% CI 1.06, 1.60). Similar trends were seen with gestational hypertension. There was no difference in all cause mortality in the three groups. The odds of a hypertensive episode were higher in women with preeclampsia (adj. OR 1.79, 95% CI 1.55, 2.05) and gestational hypertension (adj. OR 1.68, 95% CI 1.55, 1.82) compared to normotensives. Compared to normotensives, women with gestational hypertension (adj. IRR 0.91, 95% CI 0.85, 0.96) or preeclampsia (adj. IRR 0.86, 95% CI 0.77, 0.97) had lower incidences of cancer. Women with pregnancy induced hypertension are at a higher risk of incidence and mortality from ischaemic heart disease and a lower risk of cancer.

Hormonal contraception and risk of cancer.

BACKGROUND: Fear from increased cancer risk is one of the most significant reasons for low acceptance of reliable contraceptive methods and low compliance. METHODS: In this review, we included all cohort and case-control studies published in English up to December 2008. They were identified through a search of the literature using Pubmed and EMBASE. RESULTS: Data about breast cancer risk indicate a slightly increased risk among current users of oral contraceptives (OC), an effect which disappears 5-10 years after stopping. Combined OC have a significant protective effect on the risk of ovarian cancer, and the protection increases with duration of use (relative risk decreased by 20% for each 5 years of use). The significant risk reduction has been confirmed for BRCA 1 and 2 mutation carriers. The risk of endometrial cancer is reduced by about 50% in ever users, a benefit which is greater with increasing duration of use. An association has been found between increased risk of cervical cancer and long-term OC use. Current OC use has been associated with an excess risk of benign liver tumours and a modest increased risk of liver cancer. None of large prospective cohort studies with prolonged follow-up has observed an increased overall risk of cancer incidence or mortality among ever users of OC, indeed several have suggested important long-term benefits. Specifically, protective effect of OC can be used as chemoprevention in young women who are BRCA mutation carriers. CONCLUSIONS: Women wishing to use combined OC can be reassured that their decision is unlikely to place them at higher risk of developing cancer.

Patient satisfaction with GP-led melanoma follow-up: a randomised controlled trial.

BACKGROUND: There are no universally accepted guidelines for the follow-up of individuals with cutaneous melanoma. Furthermore, to date, there have been no randomised controlled trials of different models of melanoma follow-up care. This randomised controlled trial was conducted to evaluate the effects of GP-led melanoma follow-up on patient satisfaction, follow-up guideline compliance, anxiety and depression, as well as health status. METHODS: A randomised controlled trial of GP-led follow-up of cutaneous melanoma was conducted over a period of 1 year with assessment by self-completed questionnaires and review of general practice-held medical records at baseline and 12 months later. It took place in 35 general practices in North-east Scotland. Subjects were 142 individuals (51.4% women 48.6% men; mean (s.d.) age 59.2 (15.2) years previously treated for cutaneous melanoma and free of recurrent disease. The intervention consisted of protocol-driven melanoma reviews in primary care, conducted by trained GPs and supported by centralised recall, rapid access pathway to secondary care and a patient information booklet. The main outcome measure was patient satisfaction measured by questionnaire. Secondary outcomes were adherence to guidelines, health status measured by Short Form-36 and the Hospital Anxiety and Depression Scale. RESULTS: There were significant improvements in 5 out of 15 aspects of patient satisfaction during the study year in those receiving GP-led melanoma follow-up (all P

Introduction of a new incentive and target-based contract for family physicians in the UK: good for older patients with diabetes but less good for women?

AIMS: To determine whether the recording of diabetes-related health indicators has increased and differences diminished between age, gender and deprivation groups, following the introduction of the new General Medical Services contract (nGMS), an incentive- and target-based contract for UK family physicians. METHODS: A serial cross-sectional study set in 310 primary care practices in Scotland serving a population of 1.5 million registered patients, focussing on diabetic patients. Data were taken immediately before the introduction of the nGMS and after it had been in place for 1 year. RESULTS: One year after the introduction of the nGMS contract, there was a 54.2% relative increase in the number of patients electronically recorded as having diabetes. In addition, measurement of the quality indicators glycated haemoglobin (HbA(1c)), blood pressure, serum creatinine and cholesterol significantly increased (P < 0.05). Women were less likely than men to have HbA(1c)[odds ratio (OR) 0.85, 95% confidence intervals (CI) 0.80-0.91], serum creatinine (OR 0.90, 95% CI 0.84-0.96) and cholesterol recorded (OR 0.83, 95% CI 0.77-0.90) or achieve HbA(1c) (

Pharmacovigilance of over-the-counter products based in community pharmacy: methodological issues from pilot work conducted in Hampshire and Grampian, UK.

PURPOSE: The incidence of serious adverse events from non-prescription medicines remains to be established. The aim of this initial pilot work, using an observational cohort design, was to determine the feasibility of conducting a pharmacovigilance study of a non-prescription medicine, based in community pharmacies. METHOD: Community pharmacists from Grampian, Scotland, and Hampshire, England, recruited user-purchasers of ibuprofen. Exposure data were collected from a series of self-completed questionnaires. Outcome data were any new symptoms, use of concomitant medication and subsequent health-care utilization. RESULTS: A total of 1021 eligible customers were recruited, 6.4% (466/7320) and 48.2% (555/1152) by the Hampshire and Grampian networks respectively. The cohorts differed with regard to age, smoking and socio-economic status, reason for purchase and recommendation, and duration of use. The two cohorts reported different use of concomitant medication (46.0 and 65.5%), asthma (7.2 and 10.5%), stomach/peptic ulcer (3.5 and 2.1%), a higher prevalence of gastrointestinal symptoms post-compared to pre-purchase (12.9 vs. 7.2%, p = 0.0006 and 8.8 vs. 5.8%, p = 0.034), ingestion of doses in excess of the licensed non-prescription dose by 5.1 and 3.9%, and discontinuation of treatment because the medicine upset them by 4.5 and 3.1%, respectively. Most participants did not seek medical advice for their symptoms. CONCLUSION: Greater vigilance is required for adverse events that may be attributable to non-prescription product use. Development of pharmacovigilance models using community pharmacies is one means of systematically collecting information regarding drug safety. Further work is needed to identify a method which maximizes patient recruitment whilst maintaining acceptable follow-up rates.

Stopping smoking and body weight in women living in the United Kingdom.

Most studies of the effect of stopping smoking on weight in women have been cross-sectional in design and have been conducted abroad. A survey of subjects still participating in the Royal College of General Practitioners Oral Contraception Study was used to examine changes in weight among women of different smoking status and living in the United Kingdom. During roughly a 26-year period, there was a threefold increase (to 15% in 1994/1995) in the prevalence of obese (body mass index [BMI] > 30) women among the cohort. Women who stopped smoking had the largest increases in mean BMI and in the proportion of obese women at 1994/95. These results support the notion that stopping smoking leads to weight gain.

Effects of changes in smoking status on risk estimates for myocardial infarction among women recruited for the Royal College of General Practitioners' Oral Contraception Study in the UK.

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.

Using epidemiological data to guide clinical practice: review of studies on cardiovascular disease and use of combined oral contraceptives.

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.

PIP: The authors explored whether the available epidemiological data could quantify the risk of cardiovascular disease among non-smoking users of currently available, low-dose oral contraceptives under age 35 years, without medical conditions known to increase the risk of vascular disease. To that end, they reviewed all relevant published studies identified from the library of references held by the Royal College of General Practitioners' Manchester Research Unit, the reference lists of each paper, and conducted a computerized literature search of the MEDLINE database. 74 papers were identified on the relationship between the current use of combined oral contraceptives and cardiovascular disease. 23 papers reported the risk of venous thromboembolism, 22 reported data on ischemic stroke, 13 on hemorrhagic stroke or subarachnoid stroke, 13 on all stroke, and 33 on myocardial infarction. 5 papers provided information which directly address the clinical question and 14 discarded papers could have probably answered the clinical question. These findings demonstrate that much of the epidemiological data on the risk of cardiovascular disease in users of combined oral contraceptives is not useful to clinicians, although some of the discarded data could be made more useful to clinicians through reanalysis.

The influence of oral contraceptives on the risk of multiple sclerosis.

OBJECTIVE: To examine the risk of multiple sclerosis in users of combined oral contraceptives. DESIGN: Cohort study conducted between 1968 and 1996 using diagnostic data supplied by general practitioners SETTING: General practices throughout the United Kingdom. POPULATION: Royal College of General Practitioners' Oral Contraception Study cohort of initially 46,000 women recruited during the late 1960s. METHODS: Directly standardised incidence rates of multiple sclerosis were calculated for current, former and never-users of oral contraceptives using first ever cases of multiple sclerosis reported by the general practitioners. The standardisation variables were age, parity, social class and smoking history. Five-year survival rates in the different contraceptive groups were calculated using standard life table techniques. RESULTS: One hundred and fourteen first ever cases of multiple sclerosis had been reported by November 1996 during 564,000 woman-years of observation. The incidence rate in both current and former users was not materially different to that in never-users. Although based on limited evidence there was no suggestion that the five-year survival was affected by a woman's use of combined oral contraceptives. CONCLUSIONS: These findings do not suggest a greatly elevated risk of multiple sclerosis during, or after, use of combined oral contraceptives.

PIP: The influence of oral contraceptive (OC) use on the risk of multiple sclerosis was examined through use of data from a cohort study conducted in the UK in 1968-96. The Royal College of General Practitioners OC Study collected data from general practices throughout the UK on about 46,000 women. By November 1996, 114 new cases of multiple sclerosis were reported in this cohort over 564,000 woman-years of observation. The incidence rates, standardized by age, parity, social class, and smoking history, were 19.8% for current OC users, 21.9% for former OC users, and 17.1% for never users. The 5-year survival rates were 92.9%, 97.9%, and 94.6%, respectively. Although the numbers were not large enough for statistical analysis, there was some suggestion that ever use of OCs containing more than 50 mcg of estrogen increased the risk of multiple sclerosis (22.9% incidence). Overall, however, these findings do not suggest a significantly elevated risk of multiple sclerosis during, or after, use of modern low-dose combined OCs.

The risk of serious illness among oral contraceptive users: evidence from the RCGP's oral contraceptive study.

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.

PIP: Combined oral contraceptives (OCs) have been implicated with an increased risk of a number of illnesses, particularly vascular conditions such as stroke, ischemic heart disease, venous thrombosis, and peripheral vascular disease. This study assessed the balance of risk of serious illness among a cohort of OC users followed for up to 28 years. Data from the Royal College of General Practitioners' Oral Contraception Study were examined to determine the rate of such conditions during 335,181 woman-years of observation for ever-users and 228,727 woman-years for never-users. The rates were standardized for age, parity, social class, and smoking. Results of the study indicated that in comparison with never-users, ever-users had a small increased risk of any serious disease. 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 OCs containing 50 mcg or more of estrogen. In conclusion, past users of higher-dose OCs 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 OCs containing less than 50 mcg of estrogen, accompanied by the progestogen, levonorgestrel, or norethisterone acetate, do not appear to be associated with an increased net risk of serious disease.

Combined oral contraceptives and liver disease.

Although some information is available about the risk of liver tumors associated with combined oral contraceptive use, little is known about the relationship with other hepatic problems. Data from two large long-term observational studies, the Royal College of General Practitioners (RCGP) Oral Contraception Study and the Oxford-Family Planning Association (Oxford-FPA) Study, were used to examine this issue. Observations accumulated over a period of up to 27 years were available for each study. The incidence of liver disease in each study was low. There was no evidence of an increased risk of serious liver disease overall among current or former pill users. The RCGP study found a modest increased risk of mild liver disease associated with oral contraceptive use which declined after four years of use and after cessation of use. This increased risk occurred in women who had used oral contraceptives containing more than 50 micrograms of estrogen.

Combined oral contraceptives: do we know all of their effects?

Combined oral contraceptives are undoubtedly popular. By the end of the 1980's, an estimated 63 million married women around the world were using this method of contraception. In Britain, perhaps 95% of all sexually active women have used the pill at some time before their 30th birthday. Commensurate with such widespread usage, huge amounts of money have been spent during the past 35 years investigating the health effects of this method of contraception. Since it appears that all of the potential risks and benefits have now been identified, can we divert resources from pill-related research into new areas of activity. While this proposition may be attractive to funding bodies, and other researchers competing for increasingly scarce resources, it ignores the fact that several major uncertainties remain concerning the safety of combined oral contraceptives.

PIP: Despite hundreds of research studies, definitive answers on the long-term health risks associated with combined oral contraceptives (OCs) remain elusive. There is general agreement that the adverse vascular effects of first-generation OCs containing 50 mcg or more of estrogen are not influenced by duration of use and do not persist once OC use is stopped. On the other hand, the pill's protective effect against endometrial and epithelial ovarian cancer is strengthened with prolonged use and persists after discontinuation. Less certain is the impact of long-term OC use by young, nulliparous women on breast cancer risk. Also in need of investigation is the association between pill use and cervical cancer--the most common malignancy among women in developing countries. As the first generation of OC users reaches the age where long-term effects become evident, these risks can be more definitively assessed. However, the risks associated with the new, low-dose OCs will remain uncertain for several decades. Of concern is the finding that users of low-dose OCs have a greater risk of breast cancer than users of the earlier, high-dose formulations. In addition, the new pills are less suppressive of plasma gonadotropin levels and ovarian activity, raising concerns about ovarian cancer risk. Given these uncertainties, continued funding for OC research is urged.

Oral contraception and stroke. Evidence from the Royal College of General Practitioners' Oral Contraception Study.

BACKGROUND AND PURPOSE: A nested case-control analysis of data collected during the prospective Royal College of General Practitioners' Oral Contraception Study was performed to examine the relation between use of oral contraception and risk of stroke. METHODS: The 253 women who had a first-ever stroke (International Classification of Diseases, eighth revision, codes 4300 to 4389) or amaurosis fugax (code 3791) between 1968 and 1990 (case subjects) were compared with 759 women who did not have this diagnosis (control subjects). RESULTS: Smoking, social class, and history of hypertension were found to be important risk factors for stroke. Women who had ever used oral contraceptives had an increased risk of all stroke (odds ratio, 1.5; 95% confidence interval, 1.1 to 2.0, adjusted for smoking and social class) and of a fatal event (adjusted odds ratio, 2.3; 95% confidence interval, 1.2 to 4.4). A significant doubling of all stroke risk was observed among current users, an effect that was apparent in both smokers and nonsmokers. Former users had a small nonsignificant elevation in risk of all stroke but a stronger risk of a fatal event. The effects in former users appeared to be restricted to women who smoked. CONCLUSIONS: Current users of oral contraceptives appeared to be at increased risk of stroke. There is some evidence that former users may also have a persisting effect, although further research is needed to confirm these observations.

Effect of changes in maternal smoking habits in early pregnancy on infant birthweight.

BACKGROUND: The inverse relationship between maternal smoking and infant birthweight is well documented. AIM: The aim of the present study was to examine whether a change in maternal cigarette consumption in early pregnancy affects the infant's birthweight. METHOD: A total of 5980 women who presented to their general practitioners between 1976 and 1979 with an unplanned pregnancy and the babies resulting from these pregnancies were included in the study. Women were divided into four categories: non-smokers, smokers, quitters and reducers. RESULTS: In terms of mean infant birthweight, the non-smokers had a clear benefit over the smokers whose babies were 153 g lighter (P < 0.001), and over the quitters whose infants were 39 g lighter. There was also an advantage in stopping smoking: the smokers had babies whose mean birthweight was 120 g less than that of the quitters (P < 0.001). There was no demonstrable benefit from reducing cigarette consumption without entirely stopping. CONCLUSION: These findings may have important implications for where best to target health education.

Cigarette smoking and parity as risk factors for the development of symptomatic gall bladder disease in women: results of the Royal College of General Practitioners' oral contraception study.

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.

Cervical cancer and methods of contraception.

When evaluating whether the use of a particular method of contraception is associated with an increased or decreased risk of cervical cancer, it is important to be aware of the epidemiological factors which might lead to incorrect conclusions. After careful consideration of the issues, and examination of the available data, it is concluded that women who use oral contraceptives are possibly at increased risk of invasive cervical cancer; users of barrier methods probably have a decreased risk (although the protective effect may differ between the various types of barrier method); and that users of other methods of contraception do not have an altered risk.

Oral contraceptives and malignant melanoma.

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.