Benign breast disease and subsequent breast cancer: English record linkage studies.

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.

Review: post-marketing surveillance of the safety of cimetidine--the problems of data interpretation.

Experience obtained during post-marketing surveillance of the safety of cimetidine emphasizes the difficulties in interpretation posed by the high background frequency of disease of all types in drug takers. The multiple sources of confounding factors, and their high prevalence, make it impossible to detect adverse events which mimic ordinary disease, particularly when a consistent relationship between adverse event and drug exposure is not observed. The inclusion of controls emphasizes the difficulties but does not ease interpretation.

Epidemiology of carpal tunnel syndrome in women of childbearing age. Findings in a large cohort study.

There are few epidemiological data in the scientific literature about the carpal tunnel syndrome. This paper describes the characteristics of the 154 women referred to hospital for management of this condition among the 17,032 taking part in the Oxford-Family Planning Association contraceptive study. Standardized first referral rates for carpal tunnel syndrome doubled as age increased from 25-29 to 50 or more, tripled as smoking increased from zero to 25 or more cigarettes per day, doubled as total duration of oral contraceptive use increased from zero to ten years or more and doubled as Quetelet's obesity index (weight(g)/height(cm)2) increased from up to 1.99 to 2.6 or more. All these trends were statistically significant. Carpal tunnel syndrome was also found to be positively associated with a history of menstrual disorders, gastrointestinal tract symptoms and various orthopaedic conditions. The findings on cigarette smoking are of particular interest but require confirmation or refutation in another study before firm conclusions can be drawn.

PIP: Researchers analyzed 1968-1974 data of 154 women attending 1 of 17 large family planning clinics in England and Scotland and referred to a hospital for treatment of carpal tunnel syndrome (CTS) to determine CTS characteristics. The women were part of the large Oxford-Family Planning Association cohort study. A strong association between age and CTS existed, but the crude hospital referral trend (p.001) declined somewhat when considering confounding variables, e.g., smoking, (adjusted rate p.01). Cigarette smoking had a significant effect regardless of the age group (20-44 year old, p.001; 45 years plus, adjusted p.05). The researchers reported that additional research is needed to explain the mechanism involved in smoking and CTS since a mechanism is not apparent. The results showed that the longer the interval since last use of oral contraceptives (OCs) the higher the chance of acquiring CTS, but this was less significant than smoking (20-44 year old, p..01; 45 years plus, adjusted p.05). The data indicated a strong positive relationship between Quetelet's obesity index and 1st referral for CTS (20-44 year old, p..01; 45 years plus, p..05). Other significant relationships, albeit less significant than between obesity and referral, included body weight (positive) and height (negative). A negative association occurred between varicose veins and CTS. The most significant positive association between an existing disease and CTS was menstrual disorders (p=.001). Additional similar associations existed for orthopedic conditions and gastrointestinal tract symptoms. The relationships between CTS and OC use, menstrual disorders, and obesity may be related to pressure on the median nerve due to fat or edema near the carpal tunnel.

Urinary tract infection in relation to diaphragm use and obesity.

We have examined factors influencing the rate of first referral to hospital for urinary tract infection among the 17,032 women taking part in the Oxford Family Planning Association contraceptive study. The risk of first referral declined with age, was higher in nulliparous women than in parous women, was higher in non-obese than in obese women and was higher in current users of the diaphragm than in current users of other methods or no method of contraception. The main increase in the risk of referral in current diaphragm users occurred during the first 24 months when overall rates were 2-3 times higher in users than in non-users or ex-users of the diaphragm. The negative association between hospital referral for urinary tract infection and obesity was unexpected. It was not explicable in terms of age, parity or diaphragm use. It may be that obese women are less likely to receive trauma to the genital area during sexual intercourse than non-obese women because adipose tissue offers them some protection. Another possibility is that increased oestrogenization in obese women, resulting from peripheral conversion of androstenedione to oestrone, has a beneficial effect on the bladder and urethra, thus reducing the liability to infection.

PIP: Throughout England and Scotland from 1968-74, 17,032 white, married women whose ages ranged from 25-39 years were studied in an attempt to observe the correlation of urinary tract infection to diaphragm use and obesity. The risk of urinary tract infection was not found to be linked to social class and cigarette smoking. Infection was, however, found to be connected to age, parity, obesity and contraceptive use. The risk of urinary tract infection was shown to decrease with age. The risk of UTI (urinary tract infection) was found to be more prevalent among nulliparous than parous women. Women who were non-obese and women who currently used the diaphragm were at greater risk than women who were obese and women who used other/none methods of birth control. The current study along with other studies confirm that a connection exists between the use of a diaphragm and an increased risk of urinary tract infection.

Characteristics of women using different methods of contraception--some preliminary findings from a prospective study.

PIP: Some items of information collected on admission from each of 8774 women attending clinics of the British Family Planning Association up to the end of April 1971 are reported. Patients selected were willing to participate, were married, aged 25-39 years, were white British subjects, and had completed at least 5 months use of some form of contraception. Each filled out an admission questionnaire and patient and medical histories were completed. Results showed that women using oral contraceptives were younger than those using the diaphragm. IUD users were of intermediate age. Users of oral contraceptives were more frequently nulliparous. Almost all with an IUD had married early and borne 1 or more children. Most of the women interviewed were in the upper social classes, especially those using the diaphragm. Smoking was more frequent among users of oral contraceptives. Thrombophlebitis affe cted 1% of the oral contraceptive users, 5% of the diaphragm users, and 11% of the IUD users. These variations may have been due to the fact that those with a past history of thrombophlebitis would most likely have been prescribed either an IUD or a diaphragm. Although the relationship between oral contraceptives and venous thrombosis and pulmo nary embolism is now established, prospective studies are still required to provice better quantification of the risk. Analysts will need to take into consideration the strong selective factors now operating which tend to place women at highest risk from contraceptive complications in other categories of contraception use. Vaginitis and cervicitis were common in all groups but more so in those using oral contraceptives. This variation may have been due to the closer supervision of these patients.^ieng

Early oral contraceptive use and breast cancer: theoretical effects of latency.

Many cancers and other chronic diseases are associated with a long delay between exposure to a putative risk factor and subsequent diagnosis. This presents well recognised problems in the elucidation of suspected risk factors by epidemiological methods. In this paper we discuss the interpretation in epidemiological studies of the effect of a possible risk factor when population exposure is recent and rapidly changing. An important contemporary example concerns the study of early oral contraceptive (OC) use in relation to the subsequent risk of breast cancer. Computer simulations reported here indicate that plausible delays in the manifestation of any effect on breast cancer incidence make it difficult to exclude early OC use as a risk factor for breast cancer, even when large well conducted epidemiological studies show no apparent increased risk. Methods for detecting a 'latent' effect are discussed.

Myocardial infarction and angina pectoris in young women.

The Oxford-Family Planning Association contraceptive study has now followed 17,000 women, predominantly of childbearing age, for a total of more than 200,000 woman-years. The incidence of myocardial infarction and angina in women aged less than 50 years has been low: 0.03/1,000 woman-years at ages 25-34 rising to 0.67/1,000 woman-years at ages 45-49. However, the overall incidence in women who were smokers at entry to the study is more than three times that in women who were non-smokers, the increase in individual risk being proportional to the number of cigarettes smoked. Observations on other risk factors must be treated with caution in view of the small numbers involved: in general, the differences and trends reported are not statistically significant. However, a consistent positive relation is observed between incidence rates and both relative weight and parity after adjustment for age and smoking, while no consistent trend is observed for social class. Ever use of oral contraceptives is associated with a twofold increased risk of myocardial infarction (not statistically significant), but there is no increased risk in current users as was suggested by earlier studies. This may reflect the adoption of lower dose preparations and the positive selection of healthy women for oral contraception.

Oral contraception and eye disease: findings in two large cohort studies.

PIP: The relationship between oral contraceptive (OC) use and eye disease was investigated through abstraction of salient data from the two large British cohort studies of the effects of OCs: the Royal College of General Practitioners' (RCGP) OC Study and the Oxford-Family Planning Association (FPA) Contraception Study. Together, these studies have accumulated over 850,000 person-years of observation since 1968 involving 63,000 women. The conditions considered in the analysis were conjunctivitis, keratitis, iritis, lacrimal disease, strabismus, cataract, glaucoma, retinal detachment, and retinal vascular lesions. The only eye disease for which there was consistent evidence of a notable increase in risk in OC users was retinal vascular lesions. The relative risk of retinal vascular lesions in OC users compared to never users was 2.0 (95% confidence interval (CI), 1.0-3.8) in the RCGP data set and 2.4 (95% CI, 0.4-9.2) in the Oxford-FPA Study. This increased risk was not concentrated in any one diagnostic category (e.g., retinal vascular occlusion, retinal vein thrombosis, retinal hemorrhage).^ieng

Hormone replacement therapy in a risk-benefit perspective.

The relative cost-effectiveness of different treatment strategies for hormone replacement therapy (HRT) was assessed within the framework of a computer model. Where data were lacking, it was necessary to make assumptions about the effects of HRT, particularly in relation to combined oestrogen-progestogen therapy and cardiovascular disease; however, sensitivity analyses were performed to assess the impact of changing these assumptions on the cost-effectiveness equation. It appears that net expenditure by the NHS will depend critically on the direct costs of treatment, rather than on any indirect costs incurred or saved as a result of side-effects. In terms of mortality, a reduction in cardiovascular disease risk would have greatest impact and would overshadow any small increase in breast cancer risk which may be associated with long-term use. If the cardioprotective effect of oestrogen is real, our results suggest that long-term prophylactic treatment of hysterectomised women would be relatively cost-effective. Treatment of symptomatic menopausal women for any period of time appears to offer very good value for money. The lack of data relating to combined oestrogen-progestogen therapy and cardioprotection, and the major importance of the latter in the equation of benefits and risks, make it more difficult to draw conclusions about the cost-effectiveness of treating non-hysterectomised asymptomatic women for prophylactic reasons.

Oral contraceptives and reproductive factors in multiple sclerosis incidence.

Data from the Oxford.FPA prospective study show that oral contraceptive use and pregnancy have no discernible effect on the risk of developing multiple sclerosis (MS). Women of parity 0-2 developed MS twice as often as women of parity 3 or more but the difference did not reach statistical significance. Smoking may be a risk factor for developing MS. A nested case-control analysis did not identify any associations between MS onset and preceding illnesses.

PIP: Public health researchers analyzed data on 63 women who were 25-39 years old in 1968-1974 and had been followed up until at least December 1991 (the prospective Oxford Family Planning Association study in England) to study the effects of pregnancy, parity, and oral contraceptive (OC) use on the risk of developing multiple sclerosis (MS). MS onset was highest among 40-44 year olds (relative risk [RR], 1.7) and lowest among those less than 45 years old (RR, 0.4), but MS was not significantly related to age. Only 21% had developed MS symptoms by 34 years, while medical textbooks claim the peak ages to be 30-35. Women who had ever used OCs had a lower RR than nonusers (RR range, 0.5-0.8), but no trend with duration of OC use or time since last use existed. Women who had at least 3 children had a lower risk of developing MS than those of parity 2 or less and nulliparity (RR, 0.4); yet this was not significant. Further, pregnancy did not significantly affect MS onset, but there was a slight excess of low-birth-weight infants and a small deficit of miscarriages and terminations in women who later developed MS. The authors urged colleagues to conduct further research to examine the relationship between low birth weight and MS. Women who had ever smoked had a higher RR than those who had never smoked (RR for ex-smoker = 1.5, RR for 1-14 cigarettes/day = 1.6, and RR for at least 15 cigarettes/day = 1.8) and the association was almost statistically significant (p = .054). The nested case control analysis did not find any link between MS onset and preceding illnesses, including those identified by the literature as being linked with MS (bowel dysfunction, menstrual problems, endometriosis, preeclampsia/eclampsia, sinusitis, catarrh, and tonsillitis). In conclusion, the data did not provide new insights for understanding the etiology of MS.

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

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

Oral contraceptives and pregnancy in relation to peptic ulcer.

There is evidence in the scientific literature that peptic ulceration occurs less frequently during pregnancy than at other times. This encouraged us to examine the pattern of hospitalisation for peptic ulcer in the Oxford-Family Planning Association contraceptive study. In total, 175 women in the study had been hospitalised for peptic ulcer; 105 had duodenal disease, 55 had gastric disease and 22 had disease of unspecified site (some had disease at more than one location). Hospitalisation for peptic ulcer increased with age, parity and cigarette smoking. In addition, hospitalisation was at a low rate during pregnancy and was not seen at all during the 12 months following delivery. There was no relationship between hospitalisation for peptic ulcer and total duration of oral contraceptive use. Likewise, there was no significant relationship with recency of oral contraceptive use, but the lowest rate of hospitalisation was in current users of the pill.

PIP: Researchers analyzed data from the Oxford-Family Planning Association contraceptive study on 175 women hospitalized for peptic ulcer in England or Scotland to determine whether an association existed between oral contraceptive (OC) use and peptic ulcers and pregnancy and peptic ulcers. Hospitalization for peptic ulcer increased consistently with age (peptic ulcer hospitalization rate for ages 25-29 years vs. 50+ years was .3 total women years [TWY] vs. .84; p = .006). It also rose steadily with the number of cigarettes smoked/day (0.51 TWY for never smoked vs. 0.89 TWY for 15+; P = .001). It was positively associated with parity (0.6 TWY for nulliparity vs. 0.8 TWY for =or 3 children; p = .04), but parity off 1-2 appeared to have somewhat of a protective effect (0.55 TWY). Pregnant women were less likely to experience a peptic ulcer than never pregnant women (0.29 TWY vs. 0.67 TWY), but the difference was not significant. None of the once-pregnant women who had been pregnant within the last 12 months were hospitalized for peptic ulcer. Neither duration nor recency of OC use had a protective effect against peptic ulcer. Yet, current OC users did have a lower hospitalization rate for peptic ulcer than non-OC users (0.42 TWY vs. 0.68 TWY). Therefore OCs may indeed have some protective effect, but researchers must carefully design a study with a large sample size to detect any possible protective effect.

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.

The community prevalence of chronic pelvic pain in women and associated illness behaviour.

BACKGROUND: Chronic pelvic pain has often been described as a major women's health issue, but no information exists on the extent of the problem in the United Kingdom. AIM: To investigate the community prevalence of chronic pelvic pain and its effect on the lives of consulting and non-consulting women. DESIGN OF STUDY: Postal questionnaire survey. SETTING: Women aged 18 to 49 (n = 3916) randomly selected from the Oxfordshire Health Authority Register. METHOD: The questionnaire response rate (adjusted for non-deliveries) was 74% (2304/3106). Chronic pelvic pain was defined as recurrent or constant pelvic pain of at least six months' duration, unrelated to periods, intercourse, or pregnancy. Case subgroups comprised recent consulters, past consulters, and non-consulters. Women who reported dysmenorrhoea alone formed a comparison group. RESULTS: The three-month prevalence of chronic pelvic pain was 24.0% (95% CI = 22.1% to 25.8%). One-third of women reported pain that started more than five years ago. Recent consulters (32% of cases) were most affected by their symptoms in terms of pain severity, use of health care, physical and mental health scores, sleep quality, and pain-related absence from work. Non-consulters (41% of cases) did not differ from women with dysmenorrhoea in terms of symptom-related impairment. Irrespective of consulting behaviour, a high rate of symptom-related anxiety was found in women with chronic pelvic pain (31%) compared with women with dysmenorrhoea (7%). CONCLUSIONS: This study showed a high community prevalence of chronic pelvic pain in women of reproductive age. Cases varied substantially in the degree to which they were affected by their symptoms. The high symptom-related anxiety in these women emphasises the need for more information about chronic pelvic pain and its possible causes.

Benefits and risks of combined oral contraceptives.

The use of combined oral contraceptives carries a number of well-established major non-contraceptive benefits. Of these, the most important protective effects are suppression of the risk of epithelial cancer of the ovary and cancer of the endometrium. Also of great importance is a reduction in the risk of pelvic inflammatory disease. Needless to say, there are also some established risks of combined oral contraceptives. The most important of these are the vascular ones, comprising effects on acute myocardial infarction, thrombotic stroke, haemorrhagic stroke, and venous thrombosis and embolism. Possible risks which are still under evaluation include an adverse effect on breast cancer and, likewise, on carcinoma of the cervix. More information is needed about both these conditions. A number of authors have provided analyses of varying degrees of complexity in which they have attempted to weigh the benefits and risks of combined oral contraceptives. Results from some of these studies are presented in the paper. On the whole, the findings are reasonably reassuring.

Quality of life and patient preference for sequential versus continuous combined HRT: the UK Kliofem multicenter study experience. UK Continuous Combined HRT Study Investigators.

Hormone replacement therapy (HRT) must be taken for many years to attain the long-term benefits on osteoporosis and cardiovascular disease. However, this level of compliance with HRT is rarely achieved. This analysis documents the effect of continuous combined HRT with Kliogest on the relief of menopausal symptoms, and the patient preference for HRT over a 9-month treatment period. A total of 2151 postmenopausal women, of whom 1435 were currently on sequential therapy and 716 had not been previously treated, were enrolled from 55 centers in the UK. Women received a daily tablet of Kliogest for 9 months. Quality of life was assessed using the Greene Climacteric Scale, and the women completed patient preference questionnaires. Treatment with continuous combined therapy was at least as effective as previous sequential regimens in alleviating menopausal symptoms. By the study conclusion, patient preference was strongly in favor of Kliogest with 91% of completers preferring it to their previous sequential therapy. Improved quality of life and patient preference for continuous combined therapy may encourage long-term compliance with treatment, allowing more women to experience the long-term beneficial effects of HRT on osteoporosis and cardiovascular disease.

Exogenous hormones in the aetiology of cancer in women.

PIP: Both animal experimental work and epidemiological, clinical, and laboratory research on the effects of endogenous hormones in the human have made it clear that some influence of administered female sex hormones on the risk of certain cancers would be anticipated, and this has turned out to be the case. This review focuses on the administration of hormones during pregnancy, around the time of the menopause, and to prevent pregnancy. In the daughters who were exposed in utero to stilbestrol during the 1950s and 1960s, the most important effect is the development of clear cell adenocarcinoma of the vagina or cervix. Few cases of this disease have been reported before puberty, but the cumulative risk thereafter up to the age of 24 years is estimated to be between 1.4 and 4/10,000 exposed. Much less attention has been paid to the mothers who actually took the stilbestrol than to their daughters, but the published data fail to provide any convincing evidence of an increased risk of either breast or reporductive cancer among them. Regarding the administration of hormones around the time of menopause, it is well established that unopposed estrogen therapy in menopausal women can cause endometrial cancer. This has been demonstrated in a large number of case control studies reported since 1975. Most of these studies were conducted in the US and most concern the drup Premarin (conjugated equine estrogens). Some cohort studies also have been reported, and they largely support the results of the case control studies. There is now little doubt that combined oral contraceptives (OCs) protect against both epithelial ovarian cancer and endometrial cancer. Preliminary findings in the major cohort studies concerned with the longterm effects of OC use also are encouraging. A series of large case control studies conducted during the 1970s showed clearly that there is no general association between oral contraceptive use and breast cancer risk, but these large studies included few women with appreciable OC use at an early age and accordingly the publication by Pike et al. in 1981 caused much concern. Pike's study involved 163 women in Los Angeles County in whom breast cancer has been diagnosed at age 32 or less, together with a like number of neighborhood controls. Vessey et al. (1982) and the Centers for Disease control subsequently published results which did not support the California findings. Preliminary results from a new case control study conducted in Oxford and in London since 1980 suggest an increased risk of breast cancer in young women who have prolonged OC use before 1st pregnancy. The situation is very confusing and it may be some time before there is a conclusive answer. In a large cohort study conducted in Los Angeles, rates of progression from cervical dysplasia to carcinoma in situ were much higher in women using Ovulen than in women using IUDs.^ieng

Epidemiology of endometriosis in women attending family planning clinics.

OBJECTIVE: To describe the epidemiology of endometriosis in women attending family planning clinics with special reference to contraceptive methods. DESIGN: Non-randomised cohort study with follow up of subjects for up to 23 years. Disease was measured by first hospital admission rates since endometriosis can be diagnosed with accuracy only at laparotomy or laparoscopy. SETTING: 17 family planning centres in England and Scotland. SUBJECTS: 17,032 married white women aged 25-39 years at entry during 1968-74 who were taking oral contraceptives or using an intrauterine device or diaphragm. About 99% of the women approached agreed to participate and annual loss to follow up was about 0.3%. MAIN OUTCOME MEASURES: Diagnosis of endometriosis, age, parity, and history of contraceptive use. RESULTS: Endometriosis was significantly related to age, peaking at ages 40-44 (chi 2 for heterogeneity = 30.9, p < 0.001). Endometriosis was not linked to duration of taking oral contraceptives. Nevertheless, the risk of endometriosis was low in women currently taking oral contraceptives (relative risk 0.4; 95% confidence interval 0.2 to 0.7), but higher in women who had formerly taken them (1.8; 1.0 to 3.1 in women who had stopped 25-48 months previously) compared with women who had never taken the pill. A similar pattern was seen for use of intrauterine devices (relative risk 0.4 (0.2 to 0.7) in current users and 1.4 (0.4 to 3.2) in users 49-72 months previously compared with never users). No association was found between endometriosis and use of the diaphragm. CONCLUSIONS: Oral contraceptives seem to temporarily suppress endometriosis. Endometriosis may be diagnosed late in women using intrauterine devices as pain and bleeding occur with both.

PIP: Between 1968-1990, the Oxford Family Planning Association followed 313 women attending 17 family planning centers in England and Scotland who had been diagnoses with endometriosis as confirmed by laparoscopy and laparotomy to examine the epidemiology of endometriosis and its relation with contraceptive use. Only 4 women were infertile. Endometriosis rates rose significantly between the 25-29 year age group and the 40-44 year age group (0.13 vs. 0.81; p .001), so that the relative risk (RR) at 40-44 years was 6.1. Diaphragm use and endometriosis were not associated. Endometriosis was less likely to occur during pregnancy (RR = 0.05) and 4 years after pregnancy (RR = 0.4-0.6) than at most other times, but this was not significant. Current or recent (=or 12 months) use of oral contraceptives (OCs) appeared to protect against endometriosis (RR = 0.4). Yet, the risk of developing endometriosis was greater at least 1 year after stopping OC use (RR = 1.4-1.8). The researchers believed, however, that OCs only temporarily concealed the symptoms of endometriosis. Like OC use, current and recent IUD users and women who had last used an IUD 25-48 months earlier had a low risk of developing endometriosis (RR = 0.4 an 0.5, respectively). The RR increased for those who had last used an IUD at least 49 months prior to developing endometriosis (1.4). The researchers surmised that, since pain and bleeding are common clinical features of IUD use a endometriosis, providers removed the IUD rather than perform a laparoscopy or laparotomy to detect endometriosis, thereby accounting for the apparent protective effect. Further, providers probably diagnosed endometriosis later in IUD users because of the shared clinical features.

Mortality among oral contraceptive users: 20 year follow up of women in a cohort study.

OBJECTIVE: To see whether the use of oral contraceptives influences mortality. DESIGN: Non-randomised cohort study of 17,032 women followed up on an annual basis for an average of nearly 16 years. SETTING: 17 Family planning clinics in England and Scotland. SUBJECTS: Women recruited during 1968-74. At the time of recruitment each woman was aged 25-39, married, a white British subject, willing to participate, and either a current user of oral contraceptives or a current user of a diaphragm or intrauterine device (without previous exposure to the pill). MAIN OUTCOME MEASURES: Overall mortality and cause specific mortality. RESULTS: 238 Deaths occurred during the follow up period. The main analyses concerned women entering the study while using either oral contraceptives or a diaphragm or intrauterine device. The overall relative risk of death in the oral contraceptive users was 0.9 (95% confidence interval 0.7 to 1.2). Though the numbers of deaths were small in most individual disease categories, the trends observed were generally consistent with findings in other reports. Thus the relative risk of death in the oral contraceptive users was 4.9 (95% confidence interval 0.7 to 230) for cancer of the cervix, 3.3 (95% confidence interval 0.9 to 17.9) for ischaemic heart disease, and 0.4 (95% confidence interval 0.1 to 1.2) for ovarian cancer. There was a linear trend in the death rates from cervical cancer and ovarian cancer (in opposite directions) with total duration of oral contraceptive use. Death rates from breast cancer (relative risk 0.9; 95% confidence interval 0.5 to 1.4) and suicide and probable suicide (relative risk 1.1; 95% confidence interval 0.3 to 3.6) were much the same in the two contraceptive groups. In 1981 the relative risk of death in oral contraceptive users from circulatory diseases as a group was reported to be 4.2 (95% confidence interval 2.3 to 7.7) in the Royal College of General Practitioners oral contraception study. The corresponding relative risk in this study was only 1.5 (95% confidence interval 0.7 to 3.0). CONCLUSIONS: These findings contain no significant evidence of any overall effect of oral contraceptive use on mortality. None the less, only small numbers of deaths occurred during the study period and a significant adverse (or beneficial) overall effect might emerge in the future. Interestingly, the mortality from circulatory disease associated with oral contraceptive use was substantially less than that found in the Royal College of General Practitioners study.

PIP: The objective of this study is to see whether the use of oral contraceptives (OC) influences mortality. A non-randomized cohort study of 17,032 women was followed up on an annual basis for an average of nearly 16 years in 17 family planning clinics in England and Scotland. Women were recruited during 1968-74. At the time of recruitment each woman was aged 25-39, married, a white British subject, willing to participate, and either a current user of OC or a current user of a diaphragm or intrauterine device (without previous exposure to the pill). Overall mortality and cause specific mortality were measured. 238 deaths occurred during the follow-up period. The main analyses concerned women entering the study while using either OC or a diaphragm or intrauterine device. The overall relative risk of death in the OC users was 0.9 (95% confidence interval 0.7 to 1.2). Though the numbers of deaths were small in most individual disease categories, the trends observed were generally consistent with findings in other reports. Thus the relative risk of death in the OC users was 4.9 (95% confidence interval 0.7 to 230) for cancer of the cervix, 3.3 (95% confidence interval 0.9 to 17.9) for ischemic heart disease, and 0.4 (95% confidence interval 0.1 to 1.2) for ovarian cancer. There was a linear trend in the death rates from cervical cancer and ovarian cancer (in opposite directions) with total duration of OC use. Death rates from breast cancer (relative risk 0.9; 95% confidence interval 0.5 to 1.4) and suicide and probable suicide (relative risk 1.1; 95% confidence interval 0.3 to 3.6) were much the same in the 2 contraceptive groups. In 1981 the relative risk of death in OC users from circulatory diseases as a group was reported to be 4.2 (95% confidence interval 2.3 to 7.7) in the Royal College of General Practitioners OC study. The corresponding relative risk in this study was only 1.5 (95% confidence interval 0.7 to 3.0). These findings contain no significant evidence of any overall effect of OC use on mortality. Nonetheless, only small numbers of death occurred during the study period and a significant adverse (or beneficial) overall effect might emerge in the future. Interestingly, the mortality from circulatory disease associated with OC use was substantially that found in the Royal College study. (author's modified).

A randomised controlled trial of surgery for glue ear.

OBJECTIVE: To assess the effect of five different surgical treatments for glue ear (secretory otitis media) on improvement in hearing and, assuming one or more treatments to be effective, to identify the appropriate indications for surgery. DESIGN: Randomised controlled trial of children receiving (a) adenoidectomy, bilateral myringotomy, and insertion of a unilateral grommet; (b) adenoidectomy, unilateral myringotomy, and insertion of a unilateral grommet; (c) bilateral myringotomy and insertion of a unilateral grommet; and (d) unilateral myringotomy and insertion of a grommet. Children were followed up at seven weeks, six months, 12 months, and 24 months by symptom history and clinical investigations. SETTING: Otolaryngology department in an urban hospital. PATIENTS: 149 Children aged 4-9 years who were admitted for surgery for glue ear and who had no history of previous operations on tonsils, adenoids, or ears and no evidence of sensorineural deafness. Inadequate follow up information on levels of hearing and on middle ear function was obtained from 22. MAIN OUTCOME MEASURES: Mean hearing loss (dB) of the three worst heard frequencies between 250 and 4000 Hz, results of impedance tympanometry, and parental views on their child's progress. RESULTS: In the 127 children for whom adequate information was available ears in which a grommet had been inserted performed better in the short term (for at least six months) than those in which no grommet had been inserted, irrespective of any accompanying procedure. Most of the benefit had disappeared by 12 months. Adenoidectomy produced a slight improvement that was not significant, though was sustained for at least two years. The ears of children who had had an adenoidectomy with myringotomy and grommet insertion, however, continued to improve so that two years after surgery about 50% had abnormal tympanometry compared with 83% of those who had had only myringotomy and grommet insertion, and 93% of the group that had had no treatment. Logistic regression analyses identified preoperative hearing level as the single best predictor of good outcome from surgery. Other variables contributed little additional predictive power. CONCLUSIONS: If the principal objective of surgery for glue ear is to restore hearing then our study shows that insertion of grommets is the treatment of choice. The addition of an adenoidectomy will increase the likelihood of restoration of normal function of the middle ear but will not improve hearing. When deciding appropriate indications for surgery, a balance has to be made between performing unnecessary operations and failing to treat patients who might benefit from surgical intervention. Preoperative audiometry scores might be the best predictor in helping to make this decision.