Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies.

BACKGROUND: Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. METHODS: Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. FINDINGS: During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31-1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29-1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40-1·66; p<0·0001) and endometrioid (1·42, 1·20-1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07-1·46, p=0·005). INTERPRETATION: The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users. FUNDING: Medical Research Council, Cancer Research UK.

Ovarian cancer and smoking: individual participant meta-analysis including 28,114 women with ovarian cancer from 51 epidemiological studies.

BACKGROUND: Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. METHODS: Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28,114 women with and 94,942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. FINDINGS: After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1·06, 95% CI 1·01-1·11, p=0·01). Of 17,641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)<0·0001). For mucinous cancers, incidence was increased in current versus never smokers (1·79, 95% CI 1·60-2·00, p<0·0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2·25, 95% CI 1·91-2·65 vs 1·49, 1·28-1·73; p(heterogeneity)=0·01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0·81, 95% CI 0·72-0·92, p=0·001) and clear-cell ovarian cancer risks (0·80, 95% CI 0·65-0·97, p=0·03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0·99, 95% CI 0·93-1·06, p=0·8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. INTERPRETATION: The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis. FUNDING: Cancer Research UK and MRC.

Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls.

BACKGROUND: Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We aimed to assess these effects. METHODS: Individual data for 23,257 women with ovarian cancer (cases) and 87,303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use was estimated, stratifying by study, age, parity, and hysterectomy. FINDINGS: Overall 7308 (31%) cases and 32,717 (37%) controls had ever used oral contraceptives, for average durations among users of 4.4 and 5.0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average of 56 years. The longer that women had used oral contraceptives, the greater the reduction in ovarian cancer risk (p<0.0001). This reduction in risk persisted for more than 30 years after oral contraceptive use had ceased but became somewhat attenuated over time-the proportional risk reductions per 5 years of use were 29% (95% CI 23-34%) for use that had ceased less than 10 years previously, 19% (14-24%) for use that had ceased 10-19 years previously, and 15% (9-21%) for use that had ceased 20-29 years previously. Use during the 1960s, 1970s, and 1980s was associated with similar proportional risk reductions, although typical oestrogen doses in the 1960s were more than double those in the 1980s. The incidence of mucinous tumours (12% of the total) seemed little affected by oral contraceptives, but otherwise the proportional risk reduction did not vary much between different histological types. In high-income countries, 10 years use of oral contraceptives was estimated to reduce ovarian cancer incidence before age 75 from 1.2 to 0.8 per 100 users and mortality from 0.7 to 0.5 per 100; for every 5000 woman-years of use, about two ovarian cancers and one death from the disease before age 75 are prevented. INTERPRETATION: Use of oral contraceptives confers long-term protection against ovarian cancer. These findings suggest that oral contraceptives have already prevented some 200,000 ovarian cancers and 100,000 deaths from the disease, and that over the next few decades the number of cancers prevented will rise to at least 30,000 per year.

Active and passive smoking and the risk of breast cancer in women aged 36-45 years: a population based case-control study in the UK.

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

Body fatness and physical activity at young ages and the risk of breast cancer in premenopausal women.

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

Risk factors for adenocarcinoma and squamous cell carcinoma of the cervix in women aged 20-44 years: the UK National Case-Control Study of Cervical Cancer.

We report results on risk factors for invasive squamous cell and adenocarcinomas of the cervix in women aged 20-44 years from the UK National Case-Control Study of Cervical Cancer, including 180 women with adenocarcinoma, 391 women with squamous cell carcinoma and 923 population controls. The risk of both squamous cell and adenocarcinoma was strongly related to the lifetime number of sexual partners, and, independently, to age at first intercourse. The risk of both types of cervical cancer increased with increasing duration of use of oral contraceptives, and this effect was most marked in current and recent users of oral contraceptives. The risk of squamous cell carcinoma was associated with high parity and the risk of both squamous cell and adenocarcinoma increased with early age at first birth. Long duration smoking (20 or more years) was associated with a two-fold increase in the risk of squamous cell carcinoma, but smoking was not associated with the risk of adenocarcinoma. Further studies are needed to confirm the suggestion from this and other studies of differences in risk related to smoking between squamous cell and adenocarcinomas of the cervix.

Mortality and cancer incidence in persons with Down's syndrome, their parents and siblings.

A cohort study of 1425 persons with Down's syndrome (DS), and of their parents (447 mothers, 435 fathers) and siblings (1176), was set up to investigate death rates from various causes and cancer incidence patterns. In individuals with DS the all-cause death rate was six times that of the national population (SMR = 622: 95% CI 559-693), the excess being attributable to many different causes. These included: leukaemia (SMR = 1304: 95% CI 651-2334); diabetes mellitus (SMR = 982: 95% CI 267-2515); Alzheimer's disease (SMR = 22028: 95% CI 7137-51326); epilepsy (SMR = 1727: 95% CI 744-3403); and congenital anomalies (SMR = 4987: 95% CI 4175-5955). The overall survival showed marked improvements for successive birth cohorts, particularly at young ages. For mothers and fathers of persons with DS, all-cause death rates were 20% lower than national rates and there were no significant excesses from any specific cause. For siblings, all-cause death rates were similar to national rates; the only condition with a significantly raised mortality ratio was colo-rectal cancer (SMR = 793: 95% CI 216-2031), but this may well be a chance finding.

Mortality and cancer incidence in persons with numerical sex chromosome abnormalities: a cohort study.

Mortality and cancer incidence were assessed in a cohort of 1373 patients with numerical sex chromosome abnormalities diagnosed at three cytogenetics centres in Britain during 1959-90, and were compared with expectations from national rates. Four hundred patients with Turner's syndrome were followed, of whom 62 died, with a relative risk (RR) of death of 4.16 (95% confidence interval (CI) 3.22-5.39). Turner's syndrome patients had greatly raised risks of death from diseases of the nervous, cardiovascular, respiratory, digestive and genitourinary systems. One hundred and sixty three deaths occurred among 646 patients with Klinefelter's syndrome with a 47,XXY constitution, giving an RR of 1.63 (1.40-1.91). Mortality in these patients was significantly raised from diabetes and diseases of the cardiovascular, respiratory and digestive systems. There was also significantly increased mortality for patients with X polysomy (RR = 2.11 (1.43-3.02)) and Y polysomy (RR = 1.90 (1.20-2.85)), the former with significantly increased mortality from cardiovascular disease and the latter from respiratory disease. The only significantly raised risks of cancer incidence or mortality in the cohort were for lung cancer and breast cancer in patients with Klinefelter's syndrome with a 47,XXY constitution, and non-Hodgkin's lymphoma in men with more than three sex chromosomes.

Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study.

OBJECTIVE: To describe the long term effects of the use of oral contraceptives on mortality. DESIGN: Cohort study with 25 year follow up. Details of oral contraceptive use and of morbidity and mortality were reported six monthly by general practitioners. 75% of the original cohort was "flagged" on the NHS central registers. SETTING: 1400 general practices throughout Britain. SUBJECTS: 46 000 women, half of whom were using oral contraceptives at recruitment in 1968-9. Median age at end of follow up was 49 years. MAIN OUTCOME MEASURES: Relative risks of death adjusted for age, parity, social class, and smoking. RESULTS: Over the 25 year follow up 1599 deaths were reported. Over the entire period of follow up the risk of death from all causes was similar in ever users and never users of oral contraceptives (relative risk=1.0, 95% confidence interval 0.9 to 1.1; P=0.7) and the risk of death for most specific causes did not differ significantly in the two groups. However, among current and recent (within 10 years) users the relative risk of death from ovarian cancer was 0.2 (0.1 to 0.8; P=0.01), from cervical cancer 2.5 (1.1 to 6.1; P=0.04), and from cerebrovascular disease 1.9 (1.2 to 3.1, P=0.009). By contrast, for women who had stopped use >/= 10 years previously there were no significant excesses or deficits either overall or for any specific cause of death. CONCLUSION: Oral contraceptives seem to have their main effect on mortality while they are being used and in the 10 years after use ceases. Ten or more years after use ceases mortality in past users is similar to that in never users.

PIP: The Royal College of General Practitioners' oral contraception (OC) study was launched in 1968 to monitor the health of women who had used OCs. The results of the 25-year follow-up of a cohort of OC users are presented with regard to the effect of PC use upon mortality over the long term. Over 14 months from May 1968, 1400 general practitioners throughout the UK recruited to the study 23,000 women who were using OCs and a similar number who had never used them. The median age of study participants at the end of follow-up was 49 years. Over the follow-up period, 1599 deaths were reported. Over the entire period of follow-up, the risk of death from all causes was similar in ever users and never users of OCs, while the risk of death from most specific causes did not differ significantly in the 2 groups. However, among current users and those who had used OCs within the past 10 years, the relative risk of death from ovarian cancer was 0.2, 2.5 from cervical cancer, and 1.9 from cerebrovascular disease. The P-values for these relative risks are 0.01, 0.04, and 0.009, respectively. Among women who had stopped OC use at least 10 years ago, no significant excesses or deficits were observed either overall or for any specific cause of death. OCs therefore appear to have their main effect upon mortality while they are being used and in the 10 years after use is terminated.

Cigarette smoking and urinary oestrogen excretion in premenopausal and post-menopausal women.

Cigarette smoking is associated with a reduction in the risk for endometrial cancer in post-menopausal women and it has been suggested that this is because smoking has an anti-oestrogenic effect. To investigate this, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 167 premenopausal women (53 smokers, 114 non-smokers) and 200 post-menopausal women (54 smokers, 146 non-smokers). Among premenopausal women there were no significant differences in oestrogen excretion between smokers and non-smokers. Among post-menopausal women, geometric mean excretion rates for oestrone and oestradiol did not differ significantly between groups, but oestriol excretion was 19% lower (95% confidence interval -34% to -1%) in smokers than in non-smokers. This may partly explain the reduced risk for endometrial cancer among post-menopausal smokers.

A prospective study of urinary oestrogen excretion and breast cancer risk.

To test the hypothesis that high levels of endogenous oestrogens increase the risk for developing breast cancer, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 1000 women participants in a prospective study of breast cancer on the island of Guernsey. Sixty-nine subjects were diagnosed with breast cancer subsequent to urine collection. Among women who were premenopausal at the time of urine collection, cases excreted less oestrogen than controls; the odds ratios (95% CI) for breast cancer in the middle and upper thirds of the distribution of oestrogen excretion, in comparison with the lower third (reference group, assigned odds ratio = 1.0), were 0.5(0.2-1.2) and 0.4(0.2-1.1) respectively for oestrone, 0.8(0.4-1.8 and 0.4(0.2-1.1) for oestradiol, 0.7(0.3-1.6) and 0.7(0.3-1.6) for oestriol and 0.9(0.4-2.0) and 0.5(0.2-1.3) for total oestrogens. Among women who were post-menopausal at the time of urine collection, the trend was in the opposite direction, with an increase in risk associated with increased oestrogen excretion; the odds ratios were 0.9(0.3-2.2) and 1.1(0.5-2.8) for oestrone, 0.8(0.3-2.3) and 1.9(0.8-4.6) for oestradiol, 1.5(0.6-3.9) and 1.8(0.7-4.6) for oestriol and 0.9(0.4-2.6) and 1.9(0.7-4.7) for total oestrogens. The trends of increasing risk with increasing oestrogen excretion among post-menopausal women were statistically significant for oestradiol (P = 0.022) and for total oestrogens (P = 0.016). We conclude that high levels of endogenous oestrogens in post-menopausal women are associated with increased breast cancer risk, but that the relationship of oestrogens in premenopausal women with risk is unclear.

Breast cancer mortality rates are levelling off or beginning to decline in many western countries: analysis of time trends, age-cohort and age-period models of breast cancer mortality in 20 countries.

Age-standardised mortality rates for breast cancer were examined for 20 countries in Europe, North America, Australia and New Zealand from 1950 to 1992 and age-birth cohort and age-period of death models were fitted to the data. Breast cancer mortality rates generally increased in the earlier decades, but more recently rates have levelled off or begun to decline in most countries. Only in 4 of the 20 countries studied, Belgium, Hungary, Poland and Spain, was there no evidence of a decline or leveling off or mortality in recent birth cohorts or in recent years. In the other countries the decline in mortality appeared to be in part due to birth cohort effects and in part due to period effects. The birth cohort effects were suggestive of a decline in breast cancer rates among women born after about 1920 and were evident in many countries especially Canada, The Netherlands, The United Kingdom and the United States. The decline in mortality in women born after 1920 appeared to be in part related to a reduction in childlessness and a reduction in age at first birth in those generations. As well as the birth cohort effects, there was some evidence of a recent overall decline in mortality rates in several countries, e.g. Austria, FRG, Greece and the UK, and this may be due to an increase in survival resulting from improved management and treatment of women with breast cancer.

General practitioner notes as a source of information for case-control studies in young women. UK National Case-Control Study Group.

STUDY OBJECTIVE: The UK National Case-Control Study was carried out to investigate the relationship between oral contraceptive use and breast cancer risk. This study investigates whether general practitioner notes could be used as the sole data source for epidemiological studies of young women and what the effect would be on non-response and recall bias. DESIGN: Case-control study with data on gynaecological, obstetric, and contraceptive history collected at interview and from general practitioners' notes. Information from these two sources was compared. SETTING: This was a population-based study. PARTICIPANTS: Altogether 755 women with breast cancer aged under 36 years at diagnosis, each with an age-matched control, participated in the study. Response rates at interview were 72% and 89% for cases and controls but GP data were available for 90% of the 1049 case and first-selected control pairs. MAIN RESULTS: There was generally good agreement between the two data sources with respect to obstetric history and gynaecological procedures (hysterectomy, oophorectomy, and tubal ligation). The use of intra-uterine devices, or diaphragm, and partner's vasectomy were not reliably recorded in the GP's notes. The overall results of the UK study would have been qualitatively the same with respect to the relationship between oral contraceptive use and breast cancer risk if GP notes only had been used, in spite of the fact that only about half of all oral contraceptive usage was recorded in the notes. Response rates would have been higher, recall bias eliminated, and the cost of the study halved. CONCLUSIONS: When planning case-control studies in young women, the possibility of using GP notes as the primary data source should be considered. Lack of data on potential confounding factors is a possible drawback to such use. The practice of destroying GP's notes shortly after the death of patients seriously restricts the possibility of using these notes when studying rapidly fatal conditions.

Cervical cancer.

The overall incidence of and mortality from cervical cancer has declined in western countries and in most developing countries. In women under 40 years of age, however, mortality rates are levelling off or increasing in most countries. The earliest and most marked increases in young women occurred in England and Wales, Scotland, Ireland, New Zealand and Australia. Mortality rates in young women from eastern European countries began to increase later than in the UK, but the increases are of concern because baseline mortality rates are high in these countries. The reasons for the overall decline in cervical cancer are largely unknown but appear to be linked to improvements in the general standard of living. The increases in young women may well be due to the increasing prevalence of HPV infection. Screening for cervical cancer has undoubtedly led to a decline in cervical cancer incidence and mortality in many countries, but its contribution to the trends is difficult to assess without further information.

Antibodies to human papillomavirus and to other genital infectious agents and invasive cervical cancer risk.

Human papillomaviruses (HPVs) play an important part in the development of cervical cancer, but the role of other infectious agents, such as herpes simplex virus (HSV), is not clear. We assayed serum samples collected from 219 women with cervical cancer and from 387 controls for antibody to infectious agents. HPV 16-E7 and/or HPV 18-E7 antibodies were significantly related to cervical cancer risk (RR 1.9, 95% CI 1.2-3.2). Antibodies to HSV types 1 and 2, Chlamydia trachomatis, and to multiple infectious agents were associated with cervical cancer when seroprevalence rates in all cases and controls were compared, but when HPV-seropositive cases and controls were compared these associations were weaker and non-significant. This finding suggests that past infections with sexually transmitted infections other than HPV may be surrogate markers of exposure to HPV, and of no separate aetiological significance.

Spontaneous abortion and work with visual display units.

OBJECTIVE: To determine whether women who work with visual display units are at increased risk of spontaneous abortion. DESIGN: Case-control study. SETTING: Women were recruited during the three years 1987-9 from the Royal Berkshire Hospital in Reading, and from a large group practice situated within the hospital's catchment area. SUBJECTS: Cases were 150 nulliparous working women with a clinically diagnosed spontaneous abortion and controls were 297 nulliparous working women attending for antenatal care. MAIN OUTCOME MEASURES: Cases and controls were contacted and personally interviewed using the same structured questionnaire. Exposure to visual display units (VDUs) at work was assessed from information supplied at interview. RESULTS: No evidence of an increased risk of spontaneous abortion was found in women who reported that they used a VDU at work compared with women who reported that they did not (odds ratio (OR) = 0.9, 95% confidence interval (95% CI) = 0.6-1.4); and no relation with the amount of time spent actively using a VDU was evident (OR = 0.9, 95% CI = 0.5-1.6 for women who worked with a VDU for 21 hours or more each week). No effect of passive exposure to VDUs at work was found (OR = 0.9, 95% CI = 0.6-1.6 for women who reported working less than 10 feet away from a VDU that was usually switched on). These findings were not explained by maternal age, marital state, housing tenure, partner's social class, educational level, smoking, alcohol consumption, or number of previous spontaneous abortions. CONCLUSION: Given the findings and their consistency with the results from other recent studies it is concluded that pregnant women who work with VDUs are not at increased risk of clinically diagnosed spontaneous abortion. For the many women who use VDUs in their jobs, this finding provides reassurance.

A prospective study of obesity, lipids, apolipoproteins and ischaemic heart disease in women.

The aim of the study was to examine the relationships of obesity, lipids and apolipoproteins with the risk for subsequent ischaemic heart disease in middle-aged women, using a case-control study nested within a cohort study. A total of 3634 women aged 26-88 were recruited in Guernsey between 1977 and 1985 and followed until June 1986 by abstraction of their general practitioners' records. Fifty-one cases of incident ischaemic heart disease (11 myocardial infarction, 40 angina) were identified. For each case up to 4 controls were selected, matched for age and date at recruitment. Odds ratios for the development of ischaemic heart disease in the middle and upper thirds of the distribution for each variable in the controls, relative to the lowest third (and two-sided P-values for linear trends), were: 3.0, 2.6 (0.015) for Quetelet's index; 3.3, 5.1 (0.003) for total cholesterol; 0.5, 0.6 (0.102) for apolipoprotein A-I; 1.8, 2.4 (0.015) for apolipoprotein B; 1.3, 2.1 (0.155) for apolipoprotein(a). The increased risks associated with increased Quetelet's index and total cholesterol were independent of each other and these variables were more strongly related to myocardial infarction than to angina. The relationships of risk with serum cotinine, fatty acids, dehydroepiandrosterone sulphate and sex hormone binding globulin were weak and did not approach statistical significance.

Does lithium reduce the mortality of recurrent mood disorders?

Numerous follow-up studies have shown that patients with mood disorders who do not receive prophylactic medication are at increased risk of death, particularly from suicide. After 11 years follow-up we compared the mortality of 103 patients attending a lithium clinic with that expected on the basis of age/sex/year-specific rates for England and Wales. Only 10 patients died during the study, although the expected number of deaths was 18.31 (P = 0.052, two-tailed) and no deaths from suicide were observed. After correcting for the prevalence of mood disorder in the general population, the relative risk was 0.60 (95% CI 0.29-1.12) which suggests that lithium reverses the excess mortality associated with recurrent mood disorders, including that from suicide.