Skin tumours in the West of Scotland renal transplant population.

BACKGROUND: Organ transplant recipients have an increased risk of skin cancers. A specialist dermatology clinic for renal transplant recipients (RTRs) was established in 2005. OBJECTIVES: To analyse the type and incidence of skin cancers in prevalent patients in the West of Scotland after renal transplant, and to analyse the impact of the time since transplant and the immunosuppression regimen. METHODS: Skin cancer data for RTRs attending the transplant dermatology clinic over a 38-month period were collected and recorded in the West of Scotland electronic renal patient record. Skin cancer data were intrinsically linked to each individual's transplant and immunosuppression data. RESULTS: Overall, 610 patients attended. The median follow-up time from the date of first transplant was 10 years. Ninety-three patients (15.2%) had experienced a total of 368 skin cancers since transplant, and the prevalence increased with time since transplant. Basal cell carcinomas (BCCs) occurred in 74 patients (12.1%) and squamous cell carcinomas (SCCs) in 42 patients (6.9%). Three patients (0.5%) had experienced a melanoma. The SCC:BCC ratio was 0.7. Survival analysis showed significant reduction in the time to develop skin cancer in patients transplanted from 1995 onwards (P < 0.0001) and in patients who had been on triple immunosuppressant therapy at 1 year after transplant, compared with dual therapy (P < 0.0001). CONCLUSIONS: This is the first study of skin cancer in prevalent Scottish RTRs. The incidence of skin cancer is high and appears to have a direct relationship to the overall burden of immunosuppression. The SCC:BCC ratio, which is lower than reports from other centres, deserves further scrutiny.

Presence of beta human papillomaviruses in nonmelanoma skin cancer from organ transplant recipients and immunocompetent patients in the West of Scotland.

BACKGROUND: Nonmelanoma skin cancer (NMSC) has been linked to cutaneous human papillomaviruses of the genus beta (betaPV). OBJECTIVES: We sought to assess the presence of betaPV in NMSC biopsies from a group of Scottish skin cancer patients, both immunocompetent (IC) patients and immunosuppressed (IS) organ transplant recipients. METHODS: One hundred and twenty-one paraffin-embedded skin tumours (27 actinic keratosis, 41 intraepidermal carcinoma, 53 squamous cell carcinoma) and 11 normal skin samples were analysed for the presence of betaPV by a polymerase chain reaction-reverse hybridization assay designed to detect the presence of the 25 known betaPV genotypes. RESULTS: In IC patients, betaPV was detected in 30 of 59 (51%) tumours and two of 11 (18%) normal skin samples (P = 0.046). In IS patients, betaPV was found in 27 of 62 (44%) tumours; no normal skin samples were available for comparison. The most frequently found genotypes were HPV-24, HPV-15 and HPV-38. Of those tumours infected with betaPV, 28 of 57 (49%) were infected with more than one genotype (range 2-8). Tumours from IS patients were from a younger age group (mean age 57.4 years) than IC patients (mean age 73.8 years). Multiple infections were more common in tumours from IC patients (21 of 30; 70%) compared with those from IS patients (seven of 27; 26%) (P < 0.001). In the IC group, age did not appear to influence the distribution of single and multiple infections whereas in IS patients the proportion of multiple infections to single infections increased with age. There were no multiple infections in normal skin. CONCLUSIONS: A wide spectrum of betaPV types was detected in our samples. Further characterization of betaPV in vivo is needed in order to determine the mechanisms by which the virus contributes to cutaneous carcinogenesis.

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.

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 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.

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).

Combined oral contraceptives: risks and benefits.

By the age of 25 years, more than 95% of sexually active women have been exposed to combined oral contraceptives (COCs). Any effects associated with their use, therefore, carry important public health implications. COCs exert major protective effects against ovarian and endometrial cancer, which continue many years after cessation of use. COCs increase the risk of cardiovascular disease, but this risk is probably confined to current users. It is unclear whether lower dose preparations carry less risk. The precise relationship between COC use and risk of breast and cervical cancer is uncertain, although it is clear that COCs do not influence the overall risk of breast cancer. The risk-benefit equation for COC use depends crucially on assumptions about the true breast cancer risk. If there is no increased risk then COCs have a net beneficial effect on mortality, mainly due to the saving in ovarian cancer deaths. However, with more pessimistic assumptions about breast cancer, COCs have an adverse effect. The risk-benefit equation will vary for individual women. Most research has related to the developed world and extrapolation of findings to developing countries is inappropriate.

PIP: The evidence of the effects of combined oral contraceptives (COCs) on mortality and morbidity is reviewed. All the 11 case-control studies published since 1980 reported and approximate halving of endometrial cancer risk among COC users. The CASH study showed that the protective effect was apparent after 12 months' use, and users had 40% of the risk of non-users after 2 years' use. A study showed that 5 patterns of self-perceived prolonged, heavy, frequent, irregular, or painful bleeding during menstruation were reported less frequently in COC users than in users of other methods. Benign breast disease is rarer, and functional ovarian cysts are less frequent in COC users. Lower-dose preparations may carry a lower risk of myocardial infarction. Smoking possibly potentiates the risk associated with oral contraceptive (OC) use, and it is a major risk factor for myocardial infarction. The Oxford/FPA study found a 2-3-fold increase in incidence of non-haemorrhagic stroke among current OC users. The epidemiologic data on the current risk of venous thromboembolism in relation to OC use are equivocal. New lower dose COCs have a smaller adverse effect on the lipid profile: they cause a smaller increase in low density lipoprotein cholesterol (LDL) and a variable but smaller decrease in high density lipoprotein cholesterol (HDL). The large CASH study, based on 2088 cases, found a significantly elevated relative risk (2.7) of breast cancer, but only in women who had used the OC for at least 11 years. Of 6 case-control studies of hepatocellular carcinoma and OC use published since 1983, all but one showed a large elevated relative risk of around 4-fold. Delayed return of fertility has been observed in nulliparous women 30 who had 2 years; continuous exposure to COCs, although this may not be associated with low-dose, modern OCs. Malignant melanoma, pituitary adenoma, gallbladder disease, and chronic inflammatory bowel disease have been possibly associated with adverse side effects, but results are so far inconclusive.

Penicillamine-induced myasthenia in rheumatoid arthritis: its clinical and genetic features.

The clinical features and genetic background of 18 patients with rheumatoid arthritis were investigated following the development of penicillamine-induced myasthenia (PIM). The initial myasthenia symptoms in all patients consisted of variable diplopia and/or ptosis with progression to a more generalized involvement in 7 of them. No clinical, humoral, or genetic factor was determined which would allow identification of individuals developing generalized as opposed to ocular myasthenia. Withdrawal of penicillamine was associated over 4-60 weeks with a slow resolution of symptoms, facilitated in 12 patients by the use of anticholinesterase agents. In 2 patients a persistent partial unilateral ptosis remains after 15 and 25 months, while in a further patient diplopia is present 42 months after resolution of the other myasthenic symptoms. The patients with PIM when compared with a healthy 'control' population had a significant increase in HLA Dr1 (p corr less than 0.005) and an absence of HLA Dr 3. A genetic susceptibility to the development of PIM, distinct from that observed in myasthenia gravis of spontaneous onset, is suggested by this abnormal distribution of HLA Dr antigens.

Familial cheiroarthropathy without juvenile onset diabetes mellitus.

Cheiroarthropathy is a recently recognised complication of juvenile onset diabetes mellitus. It comprises inability to extend fully the fingers, contracted tendons, and waxy thickening of the skin overlying the fingers and to a lesser extent the hands. We report two families in which one parent and a number of siblings had the typical features of cheiroarthropathy without juvenile onset diabetes mellitus. The changes developed gradually during childhood and did not progress after adolescence. There were no other abnormal clinical findings, no persistently abnormal laboratory tests, and no association with a specific HLA phenotype. There are some similarities with scleroderma and its recognition is important to prevent unnecessary treatment and to reassure patients.

The completeness of cancer registration in England: an assessment from the Oxford-FPA contraceptive study.

The completeness of cancer registration in England for the period 1968-85 has been assessed in a cohort of 17,000 women who reported malignancies directly to the investigators. Of 325 cancers reported, 281 (86.5%) had been registered by mid-1987. Under-registration varied considerably between regional cancer registries. Eight (18%) of the 44 unregistered cancers were treated in private hospitals. Under-registration also varied considerably with cancer site: only 8% of 150 breast cancers were not registered, and at sites accounting for 79% of all tumours, under-registration was less than 15%; however, 40% of melanomas (20 cases) and 50% of lung cancers (6 cases) were not registered. Of 281 registered tumours, only 219 (78%) were notified to the investigators from the NHSCR at Southport, with a median lag-time of 2.5 years since diagnosis. There has been a tendency for notification of registered cancers to the investigator to become more prompt but less complete.

The effects of oral contraceptives and parity on ovarian cancer trends in women under 55 years of age.

Mortality from epithelial ovarian cancer is falling in women under 55 years of age in England and Wales. The decline does not appear to be a treatment effect nor to be attributable to changes in the rate of oophorectomy. Case-control studies have shown that high parity and oral contraceptive use are protective against the disease. We suggest that the decrease in mortality is compatible in timing and magnitude with exposure to oral contraceptives. No obvious effect on mortality attributable to parity was apparent in this analysis. Oral contraceptives may prove to be a widely acceptable means of preventing ovarian cancer, providing they do not increase breast cancer risk.

PIP: Age-specific mortality and incidence data for each calendar year (between 1950-86 for mortality and 1971-84 for incidence) were obtained from the Registrar General's Statistical Review for England and Wales and the Office of Population Censuses and Surveys publication series to consider whether the hypotheses generated by case-control studies on the effects of parity and oral contraceptive (OC) use are compatible with ovarian cancer trends in England and Wales. Rates were calculated on the basis of the mid-year female population within each 5-year age group. Initial examination of the data showed that the age-adjusted mortality rate from ovarian cancer for all women over 25 increased considerably between 1950-70 but changed little thereafter. The decline did not appear to be a treatment effect nor to be attributable to changes in the rate of oophorectomy. Case control studies have shown that high parity and OC use are protective against ovarian cancer. The disease in mortality emerges as compatible both in timing and magnitude with exposure to OCs. Ocs may prove to be an effective and widely acceptable means of preventing ovarian cancer, as long as they do not increase the risk of breast cancer.

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.

The epidemiology of hysterectomy: findings in a large cohort study.

OBJECTIVE: To examine patterns of hysterectomy in the Oxford-Family Planning Association (Oxford-FPA) study in relation to age, parity, social class and calendar period (-1974, 1975-79. 1980-84, 1985-89). DESIGN: The Oxford-FPA study is a large scale prospective study of 17,032 women recruited from 1968-74 and still under observation. SETTING: Seventeen family planning centres throughout England and Scotland. SUBJECTS: At recruitment the 17,032 women were all white, British, married, aged 25-39 and willing to co-operate. In addition, they were using the pill or an intrauterine device or a diaphragm as their method of contraception. MAIN OUTCOME MEASURE: Hysterectomy rates per 1000 woman-years of observation in various subclasses of the data. RESULTS: Up to the end of 1989, 1885 (11.1%) of the 17,032 women in the study were known to have undergone hysterectomy. Fibroids were the most common cause followed closely by menstrual disturbances in the absence of fibroids (hereafter referred to as 'menstrual disturbances'). Social class had a modest influence on hysterectomy rates. Hysterectomy for fibroids, prolapse, endometriosis and 'other reasons' showed little trend with calendar period while hysterectomy for menstrual disturbances and for cancer showed a sharp increase with calendar time especially at ages 30-39. Hysterectomy generally tended to increase with age and showed a strong relation to parity; in particular, hysterectomy for fibroids fell with parity and hysterectomy for menstrual disturbances rose sharply with parity. Using lifetable methods, it was estimated that almost 20% of the women in the study would have had a hysterectomy by age 55. CONCLUSIONS: The results give insights into factors affecting hysterectomy rates. Of particular interest is the modest influence of social class, the strong influence of parity and the rise in rates with calendar time at ages 30-39 for those undergoing hysterectomy for menstrual disturbances or cancer, but since the cohort is not directly representative of the population, some caution is required in extrapolating these findings. The estimated hysterectomy rate of about 20% by age 55 is in line with other similar estimates for the United Kingdom.

Oral contraceptives and breast cancer: latest findings in a large cohort study.

During the interval 1968-74, 17,032 women aged 25-39 years were recruited to the Oxford-Family Planning Association contraceptive study, more than half of whom were using oral contraceptives. These women have been followed up over the years and breast cancer has been diagnosed in 189 of them. We have analysed the available data in two ways. First, we have calculated standardised breast cancer incidence rates in non-users and users of oral contraceptives according to total duration of use, interval since first use, interval since last use, duration of use before first term pregnancy and duration of use before age 25. Secondly, we have conducted case-control within cohort analyses to examine the possible effects of different types of pill and to search for evidence of a latent effect of oral contraceptive use before first term pregnancy on breast cancer risk. We have found no evidence of any adverse effect of oral contraceptive use on the risk of breast cancer in this study. There was, however, little exposure to the pill before first term pregnancy among the participants and virtually no such exposure at a very young age (i.e. below 20 years). Accordingly, the results of this study strengthen the evidence that oral contraceptive use by mature women does not increase breast cancer risk, but add little to the uncertainty about the effects of early use.

PIP: No evidence of increased risk for breast cancer was found in a study of potential adverse effects of oral contraceptives use. The 1988 study was based on 189 diagnosed cases of breast cancer among 17,032 women aged 25-39 in England and Scotland during 1968-74. More than half of all the women studied were using an oral contraceptive. The study examined breast cancer incidence rates in nonusers and users of oral contraceptives according to total duration of use, interval since 1st use, interval since last use, duration of use before 1st term pregnancy, and duration of use before age 25. The study also attempted to analyze possible effects of different types of pills and search for latent effects of oral contraceptive use before 1st-term pregnancy on breast cancer risk. The study supports other studies showing that the use of oral contraceptives by women during the middle fertile years (ages 25-39) has no adverse effect on breast cancer risk. Because so few women included in the study were younger than age 25, the study's findings were inconclusive regarding the risk of breast cancer associated with early use of oral contraceptives. Regarding the possible effects of different types of pills and the possible latent effects of oral contraceptive use before 1st-term pregnancy, the study was unable to discern any clear pattern or trend.