Valerie Beral

Mortality of Shipham residents: 40-year follow-up.

The 1939 populations of Shipham, a village in Somerset with high soil-cadmium levels, and a nearby control village have been followed for 40 years. Death certificates were obtained for those who had died, and the mortality rates were compared with those for England and Wales. Small excesses of hypertensive, cerebrovascular, and genitourinary disease were noted in Shipman but not in the control village. These conditions have been associated wih cadmium toxicity, and so it is possible that cadmium had some influence on the disease pattern in Shipham; but if so, the effect was slight. By contrast, fewer deaths than expected from respiratory disease and cancers were observed in both villages. This gave rise to all-cause mortality rates in Shipham and the control village which were similar and well below the national average.

Oral contraceptive use and malignancies of the genital tract. Results from the Royal College of General Practitioners' Oral Contraception Study.

Of 47,000 women followed since 1968, those who had used oral contraceptives (ever-users) had a significantly higher incidence rate of cervical cancer than never-users. After standardisation of rates by age, parity, smoking, social class, number of previously normal cervical smears, and history of sexually transmitted disease, the excess was 41 per 100,000 woman-years for carcinoma-in-situ and 8 per 100,000 woman-years for invasive cervical cancer. Incidence increased with increasing duration of use: the standardised incidence rate for cervical cancer in women who had taken the pill for more than 10 years was four times than in never-users. Ever-users had a lower incidence of other uterine cancers (deficit 5 per 100,000 woman-years); a lower incidence of ovarian cancer was also found (deficit 4 per 100,000), but was not statistically significant. Overall, ever-users had an excess incidence for genital tract cancers 37 per 100,000 woman-years. This excess was mainly from carcinoma-in-situ of the cervix; the excess incidence of invasive cervical cancer was offset by the deficits in other uterine and ovarian cancers. Standardised mortality rates from genital cancer were similar in ever-users and never-users. Of relevance to clinical practice is the substantially different distribution of primary cancer sites: cervical cancer accounted for 75% of the invasive genital cancers and 74% of deaths from genital cancer in ever-users, but only 31% of the invasive cancers and 30% of deaths in never-users.

Cancer of the cervix: A sexually transmitted infection?

n It has been established that sexual activity is a major factor in the genesis of cervical cancer. There are 2 current etiological hypotheses based on these observations. The 1st hypothesis stresses the association of cervical cancer with factors related to an early age at 1st intercourse. The 2nd hypothesis stresses the association of cervical cancer with factors related to the multiplicity of sexual partners, not only of the woman herself, but also of her husband. It proposes that malignant change is induced by a sexually transmitted infection. It is assumed that during a womans life her risk of exposure to gonorrhea is limited to a relatively short period in early adulthood. It is also assumed that a womans chance of becoming infected depends on the level of gonorrhea in the community when her risk of infection is greatest, i.e., the incidence of gonorrhea when she is aged 20. When mortality patterns for cancer of the uterine cervix were compared with trends in incidence of sexually transmitted diseases in both England and Wales and in Scotland, there were striking associations between the temporal, social class, occupational, and geographic distributions of these diseases. The data examined were mortality rates from cervical cancer in successive generations of women in England and Wales born between 1902 and 1947 and between 1902 and 1942 for Scotland. The data were taken from the annual reports of the Registrar Generals of England and Wales and of Scotland. Both venereal disease and cervical cancer mortality are more common in urban areas and around seaports than in the country as a whole. Cervical cancer mortality shows a strong social class gradient. Social class is determined by occupation, and for married women by husbands occupation. Wives of professional men experienced mortality rates only 35% as high as the rates for all married women, and wives of unskilled laborers experienced rates 181% of those of all married women. The correlation between mortality from syphilis among males and cervical cancer in their wives was pronounced, both by social class and by occupation. In sum, the data suggest that exposure to sexually transmitted infection is an important determinant of cervical cancer. If cervical cancer prevention and therapy remain unchanged, the high risk of death from cervical cancer of the generation of women born after 1940 will probably continue to operate throughout their lives.n

Cutaneous factors related to the risk of malignant melanoma.

In a case‐control study, 287 women with malignant melanoma were compared with 574 age‐matched controls. Red hair colour at age 5 years was associated with a tripling of risk [relative risk (RR) = 3.0], blonde hair with a 60% increase (RR=1.6) and fair skin with a doubling (RR = 2.1). Women with melanoma also reported that they tended to burn (RR = 1.4) and to freckle (RR =1.9) after exposure to sunlight. Since fair skin, red hair, and the tendency to burn or freckle after exposure to sunlight all cluster in the same individuals, the extent to which each of these factors had an independent influence on susceptibility to melanoma was investigated. Hair colour, especially red hair, proved to be the major determinant, followed by skin colour.

An epidemiological study of recent trends in ectopic pregnancy.

Data from two independent sources in England and Wales, the first based upon persons discharged from hospital and the second upon general practitioner consultations, indicate that the incidence of ectopic pregnancy has been increasing since the late 1950s, with a particularly sharp increase since 1970. Time trends in the age and regional distribution of ectopic pregnancy suggest that the increasing use of intrauterine contraceptive devices may be a major factor contributing to this recent increase in extrauterine gestations. In contrast, recent age and regional trends in tubal infection appear to be unrelated to the trends in ectopic pregnancy. The possible contribution of progestogen‐only contraceptives, induced abortion and tubal surgery to the recent increase in extrauterine pregnancy cannot be assessed from the available data.

CARDIOVASCULAR-DISEASE MORTALITY TRENDS AND ORAL-CONTRACEPTIVE USE IN YOUNG WOMEN

Analysis of mortality trends in 21 countries indicates that, since oral contraceptives first became available, changes in mortality from non-rheumatic heart-disease and hypertension (I.C.D. 400-429), cerebrovascular disease (I.C.D. 430-439), and all non-rheumatic cardiovascular diseases (I.C.D. 400-469) among women aged 15-44 years have been strongly associated with changes in the prevalence of oral-contraceptive use in each country. This relationship is highly specific for women of reproductive age. The relative risks of death from heart-disease and hypertension, cerebrovascular disease, and all cardiovascular diseases for women using oral contraceptives compared with non-users were estimated to be 5 to 1,2 to 1, and 3 to 1 respectively. These findings suggest that the range of vascular diseases affected by oral-contraceptive use and the size of the associated risks may be greater than previously recognised. Furthermore, the increased risks of cardiovascular disease might exist not only with the pills containing high oestrogen doses, but also with the new lower dose pills.

DOES PREGNANCY PROTECT AGAINST OVARIAN CANCER

A clear inverse relation between average completed family size and mortality from ovarian cancer in different populations of women is seen from one country to another; for successive generations of women living within the same country; in married and single women; and in different social, religious, immigrant, and ethnic groups. The findings suggest that pregnancy--or some component of the child-bearing process--protects directly against ovarian cancer. This protection seems to persist throughout life. The more-than-twofold increase in the age-standardised ovarian-cancer death-rate in England and Wales since 1931 can be explained largely by changes in the average completed family size.

Cholecystectomy and changing mortality from gallbladder cancer.

Over the past decade, mortality from gallbladder cancer has declined sharply in England and Wales, Scotland, the United States, and Canada, but has risen by 33% in Sweden. In all these countries, gallbladder cancer mortality rates are inversely related to cholecystectomy rates in the previous year. It is suggested that changes in cholecystectomy rates produce changes in the prevalence of cholelithiasis, and consequently in gallbladder cancer incidence and mortality. It is estimated that 1 fewer death from gallbladder cancer occurs for about every 100 cholecystectomies done during the preceding year. The possibility of preventing death from gallbladder cancer in the patient with asymptomatic cholelithiasis must be balanced, however, against the risks of surgery.

Fetal loss, gravidity, and pregnancy order.

An investigation of the reproductive history of 3068 women doctors showed that the risk of fetal loss at a given pregnancy order varied with their gravidity--that is, the total number of pregnancies that has occurred before the survey. Fetal loss rates in even the first pregnancy varied with eventual gravidity in a J-shaped manner. They fell from 12.4% in women with only one pregnancy at the time of the study, to 5.7% in women with two, and then increased steadily to 36.8% in those with six pregnancies. This variation in risk remained when allowance was made for the incomplete nature of some of the reproductive histories. When gravidity was held constant, fetal loss rates decreased with each successive pregnancy. This finding conflicts with previous suggestions that the risk of fetal loss increase with pregnancy order and age.

POOR REPRODUCTIVE OUTCOME IN INSULIN-DEPENDENT DIABETIC WOMEN ASSOCIATED WITH LATER DEVELOPMENT OF OTHER ENDOCRINE DISORDERS IN THE MOTHERS

In a prospective study of insulin-dependent diabetic women who in the 1950s were involved in a drug trial, 13 (14%) of those who were still alive 27 years later were reported to have acquired thyroid disease or pernicious anaemia during the follow-up period. This suggests that their diabetes mellitus was a manifestation of a more generalised polyendocrine disorder. The pregnancy history of these 13 women differed strikingly from that of the other 82 insulin-dependent diabetic women: in the diabetic women who subsequently acquired other endocrine disease 69% of pregnancies resulted in a fetal or infant death, compared with 44% in other insulin-dependent diabetic women (p less than 0.01). This risk increased with pregnancy order, the odds ratio of an unfavourable outcome in women who later acquired thyroid disease or pernicious anaemia, compared with the other diabetic women, being 1.2 for the first pregnancy, 3.1 for the second pregnancy, 7.3 for the third pregnancy, and 14.0 for the fourth pregnancy. The mean birthweight of offspring of the women with other endocrine disease was substantially lower than the mean birthweight of offspring of other diabetic mothers (2977 g and 3430 g, respectively). These differences in birthweight and mortality could not be explained by the severity of the mothers diabetes at the time of their pregnancies, and were evident even before the diabetes was diagnosed.