Are the effects of risk factors for timing of menopause modified by age? Results from a British birth cohort study

OBJECTIVES: This study investigated the influence of mother's age at menopause, early life and adult behavioral factors on the timing of menopause until age 57 years, and whether these effects vary according to the women's age at menopause. DESIGN: A nationally representative cohort of 1,583 British women born in March 1946 with prospective data across the life course. For factors that vary with age at menopause, analyses were stratified by age at menopause younger than 50 years or 50 years or older. RESULTS: Cox regression models indicated that for women with earlier menopause, those who were heaviest at 2 years had a 59% lower hazard ratio for menopause than those who were the lightest (hazard ratio [HR]=0.41, 95% CI: 0.16-1.01), whereas this figure was 35% lower (HR=0.65; 95% CI: 0.42-1.00) for the later menopause group. For women in the earlier group with parental divorce during childhood, the HR was 6.5 (95% CI: 2.021.3) times higher than that of other women. This rate decreased to 2.5 (95% CI: 1.5-4.2) for those with later menopause. In both groups, increasing mother's age at menopause was associated with decreasing HR (P<0.0001). For all women, being breast-fed (P=0.05), increasing cognitive ability (P=0.009), and increasing parity (P=0.001) delayed menopause. CONCLUSIONS: This study found that the impact of weight at 2 years, parental divorce during childhood, and mother's age at menopause varied according to the women's age at menopause. There was further evidence that being breast-fed, higher childhood cognitive ability, and increasing parity delayed menopause. These results suggest the interaction of genetic and environmental factors in determining age at menopause.     

Does early growth influence timing of the menopause? Evidence from a British birth cohort

BACKGROUND: Few adult environmental or behavioural factors have been consistently associated with age at menopause. The peak number of follicles attained in utero or lost before ovulation begins may be more important. This study investigates whether birthweight, childhood body size, having been breastfed and early socioeconomic circumstances are associated with age at menopause. METHODS: Menopausal status and risk factor information have been collected prospectively from 1572 British women followed up since their birth in 1946, so far until 53 years. Cox's regression models were used to investigate the relationships between early life factors and rate of menopause. RESULTS: Age at menopause varied by duration of breastfeeding, weight at age 2 years, childhood socioeconomic status, but not birthweight. In a multiple regression model, women of low weight at 2 years had an earlier menopause [hazard ratio (HR) = 0.75 for highest versus lowest quarter: 95% confidence interval (CI) 0.54-1.02] and those who had been breastfed had a later menopause (HR = 0.69 for vertical line 7 months versus never breastfed: 95% CI 0.51-0.92) than others. The influence of socioeconomic status was attenuated. CONCLUSIONS: Early life influences may influence ovarian ageing, highlighting the importance of investigating factors from across the life course.     

Cognitive function across the life course and the menopausal transition in a British birth cohort

OBJECTIVE: Despite biological plausibility, relationships between menopause and cognitive function are inconsistent. We investigated whether menopause status and menopause age were associated with general cognitive ability, verbal memory, and visual search speed and concentration in a large cohort of women while considering vasomotor and psychological symptoms, previous childhood and adult measures of cognitive function, lifetime socioeconomic circumstances, educational attainment, lifestyle factors, and chronic diseases. DESIGN: A nationally representative British cohort of 1261 women born in March 1946 and all aged 53 years at cognitive testing, with prospective information on previous cognitive function, menopausal characteristics, and potential confounders. RESULTS: There was only weak evidence of the effect of natural menopause on cognitive function and no evidence of any effects of hormone therapy use or hysterectomy status. There was a trend across the phases of the natural menopausal transition (pre-, peri-, and postmenopause) for the National Adult Reading Test (P = 0.005) and search speed and concentration (P = 0.042), with postmenopausal women having the lowest cognitive function, but there was no trend in verbal memory. Variation in vasomotor and psychological symptoms did not explain these trends. In postmenopausal women, there was a positive trend across menopause age for verbal memory (P = 0.004) and a weak positive trend for the National Adult Reading Test (P = 0.052), with women who reached menopause later having higher cognitive function. Previous cognitive function generally explained the associations, which were further weakened by adjusting for socioeconomic and educational confounders. One exception was the association between the natural menopause transition and search speed and concentration, which remained after adjustment for these factors. CONCLUSION: Menopause adversely affects cognitive function, but this effect may be largely explained by premenopausal cognitive function. These findings suggest that common environmental or genetic factors, operating through long-term or lifelong hormonal mechanisms, may influence the timing of natural menopause and lifetime cognitive function.     

Age at natural menopause and cognition

OBJECTIVES: To examine associations between age at natural menopause, childhood IQ and cognition at age 65 years. To determine if lower age at menopause partly mediates the effect of childhood IQ on cognition at age 65 years. METHODS: Data were provided by a sub-cohort of women participating in a longitudinal study of brain ageing and health. Main variables were childhood IQ from a 1947 national survey of children born in 1936, age at natural menopause and five cognitive tests measured in 2000-2001. RESULTS: Age at menopause was associated with childhood IQ (r = 0.221, P = 0.008) and with general cognitive function age 65 years (r = 0.246, P = 0.004). Multiple regression showed 44.4% of the reliable variance in cognitive ability age 65 years is contributed by IQ at an age of 11 years to which, years of education contributed an additional 3.9%. Structural equation modelling suggested that childhood IQ differences contribute 4.8% of the variance to age at natural menopause and that the relation between age at menopause and cognition at age 65 years was accounted for by childhood IQ. CONCLUSION: Childhood IQ and age at menopause each have significant relations with general cognitive function age 65 years but the link between cognition age 65 years and age at menopause might be wholly explained by childhood IQ. The association between childhood IQ and age at menopause may be attributed to central neural mechanisms or, as argued here, to the effects of childhood IQ on adult general health.     

Body mass index trajectories and age at menopause in a British birth cohort

OBJECTIVE: This study investigates the influence of body mass index (BMI) at ages 15, 20, 26, 36, and 43, and of BMI trajectories from 20 to 36 years on the timing of menopause and hormone therapy (HT) use until age 57 years. METHODS: A nationally representative British cohort of 1583 women born in March 1946 with prospective data across the life course. RESULTS: By age 57, a total of 695 women had experienced natural menopause while 431 women had started HT prior to menopause. Cox regression models indicated no significant associations between BMI at any age, or BMI trajectory, and timing of natural menopause. At every age BMI was strongly (p< or =0.01) and linearly associated with age at HT use and BMI from 26 years onwards was associated with age at first event (menopause or HT use). Decreasing BMI was associated with earlier HT use at all ages. These associations were not accounted for by parity, cigarette smoking or childhood and adult social class. CONCLUSION: BMI across the reproductive lifespan did not influence age at menopause to an extent that would be clinically relevant for postmenopausal health. Lower BMI at all ages and underweight trajectory were related to an earlier start of HT. Further studies are required to understand whether such relationships are due to underweight women experiencing menopause earlier (and because of menopausal symptoms starting HT earlier) than heavier women, or having behavioural characteristics related to earlier HT use, independent of menopause.     

Childhood exposure to the 1944-1945 Dutch famine and subsequent female reproductive function

BACKGROUND: Childhood caloric restriction may lead to permanent changes in the hypothalamo-pituitary-gonadal axis, which could lead to impaired female reproductive ability. We assessed the effect of childhood exposure to the 1944-1945 Dutch famine on subsequent female reproductive function. METHODS: This was a population-based cohort study in Utrecht, The Netherlands. Between 1983 and 1985, 6030 women born between 1932-1941 were classified by questionnaire according to their famine exposure experiences. Dates of marriage, first and second childbirth, and information on a medical reason for having no children or fewer children than wanted were available from questionnaires, as well as ages and type of menopause. RESULTS: Severe famine exposure during childhood significantly decreased chances of first and second childbirth at any given time after marriage or first childbirth [adjusted hazard ratios (HR) 0.86, 95% confidence interval (CI) 0.76-0.96; and HR 0.87, 95% CI 0.78-0.97, respectively). Risk of a medical reason for having no or fewer children than wanted was increased in the severely exposed (odds ratio 1.88; 95% CI 1.29-2.74), as was the risk of a surgical menopause (HR 1.53; 95% CI 1.27-1.84). CONCLUSIONS: Our findings support the presence of longstanding modest effects of childhood famine exposure on reproductive function in women.     

Oral contraceptive use in relation to age at menopause in the DOM cohort

BACKGROUND: We investigated the hypothesis that long-term use of oral contraceptives (OCs), in particular high-dose OCs, could postpone age at menopause. METHODS: Data was used from 8701 women who participated in a breast cancer screening programme in Utrecht (DOM-3 cohort), and who did not use hormone replacement therapy (HRT) or OCs in the 4 years prior to their last menses. Data on OC-use, menopausal status, age at menopause, year of birth, parity, smoking behaviour, socio-economic status, body mass index and age at menarche was available. Use of high-dose OCs has been defined in this study as OC-use before 1972. The data was analysed by means of linear regression and Cox's proportional hazards analysis. Women still menstruating, women with surgical menopause and women lost to follow-up were censored at their last known date of menstruation. Endpoint was the natural menopause (n = 4589). RESULTS: The use of high-dose OCs advanced the onset of menopause by approximately 1.2 months for every year of OC-use compared with no OC-use. High-dose OC-use for > or = 3 years, adjusted for confounding variables, increased the risk of earlier menopause compared with no OC-use (adjusted hazard ratio 1.12; 95% CI 1.03--1.21). The use of lower dose OCs did not increase the risk of earlier menopause (adjusted hazard ratio 1.00; 95% CI 0.91--1.09). CONCLUSIONS: These results are inconsistent with the hypothesis that long-term use of OCs could postpone the onset of menopause by inhibiting follicle depletion. Possible explanations are discussed.     

Scholastic achievement at age 16 and risk of schizophrenia and other psychoses: a national cohort study

BACKGROUND: There is abundant evidence that schizophrenia is associated with cognitive deficits in childhood. However, previous studies investigating school performance have been inconclusive. Furthermore, there are several biological and social factors that could confound the association. We investigated whether school performance at age 16 is associated with risk of adult schizophrenia and other psychoses in a large national cohort, while controlling for multiple confounders. METHOD: Using a national sample of 907 011 individuals born in Sweden between 1973 and 1983, we used Cox regression to assess whether scholastic achievement at age 15-16 predicted hospital admission for psychosis between ages 17 and 31, adjusting for potential confounders. RESULTS: Poor school performance was associated with increased rates of schizophrenia [hazard ratio (HR) 3.9, 95% confidence interval (CI) 2.8-5.3], schizo-affective disorder (HR 4.2, 95% CI 1.9-9.1) and other psychoses (HR 3.0, 95% CI 2.3-4.0). Receiving the lowest (E) grade was significantly associated with risk for schizophrenia and other psychoses in every school subject. There was no evidence of confounding by migrant status, low birthweight, hypoxia, parental education level or socio-economic group. CONCLUSIONS: Poor school performance across all domains is strongly associated with risk for schizophrenia and other psychoses.     

Caloric restriction reduces age at menopause: the effect of the 1944-1945 Dutch famine

OBJECTIVE: To assess the effect of caloric restriction, as endured during the 1944-1945 Dutch famine, on the age at which natural menopause occurs and to identify specific vulnerable age periods in which caloric restriction has the largest effect. DESIGN: This was a population-based cohort study conducted in Utrecht, the Netherlands. Between 1983 and 1986, 9,471 women aged 40 to 73 years at the time of interview were classified regarding their exposure to the famine. Age at natural menopause was obtained from all available data, retrospectively as well as prospectively. We estimated differences in mean age at natural menopause between famine exposure categories (not, moderately, and severely exposed), with adjustment for smoking, parity, socioeconomic status, body mass index, age at menarche, and year of birth. RESULTS: Women experienced natural menopause on average 0.36 years earlier (95% CI: -0.60, -0.11) when severely exposed to the famine and 0.06 years earlier (95% CI: -0.22, 0.09) when moderately exposed compared with the unexposed women. This effect was particularly pronounced in those severely exposed from 2 to 6 years of age: -1.83 years (95% CI: -3.03, -0.63). CONCLUSIONS: Our findings suggest that caloric restriction decreases age at natural menopause. Early childhood seems to be a particularly sensitive age period for this effect.     

Sun exposure and age at natural menopause: a cross-sectional study in Turkish women

OBJECTIVES: In a cross-sectional study of 157 Turkish women attending outpatient clinics of a university hospital during April-May 2003, association between various subject characteristics and menopause timing was investigated. METHODS: Characteristics were self-reported by women aged 45-60. Of the lifestyle factors, sun exposure, physical activity, food intake and dressing with headscarf were obtained as recalled average lifelong practices up to time of menopause. Cox proportional hazard modeling was used, censoring for hysterectomy, oopherectomy and HRT use. RESULTS: Median age at natural menopause was 52 years. In multivariate analysis, earlier natural menopause was associated with low level of lifelong sun exposure (HR=6.381, 95% CI: 2.996-13.588, p< or =0.0001), heavy physical activity (HR=2.335, 95% CI: 1.305-4.177, p=0.0043), current calcium supplement use (HR=3.191, 95% CI: 1.361-7.485, p=0.0076), diagnosis of hypertension (HR=2.002, 95% CI: 1.186-3.378, p=0.0093), not owning a house (HR=3.002, 95% CI: 1.148-7.852, p=0.0250) and longer years on oral contraceptives (HR=1.085, 95% CI: 1.000-1.176, p=0.0487). Engagement in farming (HR=2.043, 95% CI: 1.056-3.952, p=0.0339), height (cm) (HR=0.953, 95% CI: 0.907-0.994, p=0.0279) and fish consumption (servings/week) (HR=0.600, 95% CI: 0.375-0.960, p=0.0331) were associated with age at menopause in univariate analysis only. For n=109 women who recalled whether maternal menopausal age was <50 or > or =50, sun exposure (HR=7.221, 95% CI: 2.971-17.547, p<0.0001) was a stronger predictor of age at natural menopause than maternal menopausal age (HR=2.882, 95% CI: 1.477-5.621, p=0.0019). CONCLUSIONS: We identify some previously unrecognized correlates of age at natural menopause, namely self-reported lifelong sun exposure, lifelong physical activity, house-ownership, current use of calcium supplements, and lifelong fish consumption. These findings should be confirmed in larger studies.     

A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity

BACKGROUND: Anti-Müllerian hormone (AMH) inhibits primordial follicle recruitment in the mouse ovary. We hypothesize that in women AMH signaling also regulates the usage of the primordial follicle pool and hence influences the onset of menopause. Since age at menopause has a strong genetic component, we investigated the role of AMH signaling using a candidate gene approach. METHODS: In two large population-based cohorts of Dutch post-menopausal women (n = 2381 and n = 248), we examined the association between two polymorphisms, one in the AMH gene and one in the AMH type II receptor (AMHR2) gene, and natural age at menopause. RESULTS: The AMH Ile(49)Ser polymorphism (rs10407022) was not associated with age at menopause in either cohort. In the Rotterdam cohort, the AMHR2 -482 A > G polymorphism (rs2002555) was associated with age at menopause in interaction with the number of offspring (P = 0.001). Nulliparous women homozygous for the G-allele entered menopause 2.6 years earlier compared with nulliparous women homozygous for the A-allele (P = 0.005). In the LASA cohort, women with the G/G genotype tended to enter menopause 2.8 years earlier compared with the A/A genotype (P = 0.063). CONCLUSIONS: The observed association of the AMHR2 -482 A > G polymorphism with natural age at menopause suggests a role for AMH signaling in the usage of the primordial follicle pool in women.     

Time-related trends of age at menopause and reproductive period of women in a Chuvashian rural population

OBJECTIVE: The objective of this study was to examine in an observational, cross-sectional, community-based study the secular trend of age at menopause among women in a rural Chuvashian population and to identify factors associated with age at menopause. DESIGN: The sample included 316 postmenopausal women born between 1920 and 1950 with mean age at menopause of 48.47 +/- 4.63 (34-58) years. Statistical analyses included simple and multiple linear regression and "whiskers" plots. RESULTS: Significant association was found between year of birth and age at menopause (beta = 0.194, P < 0.001) and reproduction period (P = 0.193, P < 0.001). Mean values of age at menopause increased from 47.0 years (born during 1920-1925) to maximal values of 49.7 years (born during 1940-1945) and 49.3 years (born during 1945-1950). Mean values of their reproductive period increased from 30.7 (born during 1920-1925) to maximal values of 34.1 (born during 1940-1945) and to 33.7 (born during 1945-1950). Multiple linear regression analysis demonstrated that year of birth was the only statistically significant (P = 0.19, P < 0.01) predictor of age at menopause. Age at menarche can also be a possible predictor of age at menopause (beta = -0.12, P = 0.04). CONCLUSIONS: The study confirmed certain secular trends of age at menopause and reproductive periods in Chuvashian women. The authors also observed a negative association between age at menarche and age at menopause. The number of children and medical abortions as well as body mass index showed no association with age at menopause.     

Season of birth influences the timing of menopause

BACKGROUND: Seasons may influence prenatal growth and future fertility. This study investigated whether season and month of birth influenced the timing of menopause in a group of women attending three Italian menopause clinics. METHODS and RESULTS: Age at menopause of 2822 post-menopausal women (>12 months of amenorrhoea) was stratified by month and season of birth. Mean age at menopause was 49.42 years (SEM: 0.78 years). Menopause occurred earlier for women born in the spring (age 49.04+/-0.15 years) than in the autumn (49.97+/-0.14 years). The earliest menopause was found in women born in March (48.9+/-0.25 years) and the latest in women born in October (50.3+/-0.25 years). The effect of season of birth on age at menopause remained even when considering factors that in our analysis were capable of significantly interfering with the timing of menopause, such as age at menarche, body mass index, smoking habit, level of education and type of job. CONCLUSIONS: Taking into consideration the retrospective design of the study, and a possible recall bias, the present data seem to suggest that environmental factors linked to seasons are capable of interfering with the timing of a woman's ovarian exhaustion by an action exerted in the prenatal period.     

How the 1932 and 1947 mental surveys of Aberdeen schoolchildren provide a framework to explore the childhood origins of late onset disease and disability

Objectives

To describe the discovery and development of the Aberdeen 1921 and 1936 birth cohort studies.

Study Design

The Aberdeen birth cohort studies were started in 1998 when the Scottish Mental Survey archives of the Scottish Council for Research in Education were re-discovered and permissions granted to follow-up survivors born in 1921 or 1936 and then aged about 77 or 64 years and who had entered (or were about to enter) the age of greatest risk for Alzheimer's disease (AD).

Main outcome measures

Sources of attrition from the study, exposures to childhood adversity, nutritional, genetic and life style factors of possible relevance to extent of age-related cognitive decline and the timing of onset of dementia.

Results

By 2010, the feasibility of following up more than 75% of Scottish Mental Survey survivors living in the Aberdeen area without dementia was well-established, dementia ascertainment to age about 88 years was completed in the 1921 birth cohort and was underway in the 1936 born cohort.

Conclusion

These databases are available to other bone fide research groups wishing to test specific hypotheses that may either replicate their own findings or make best use of the data collected in the Aberdeen studies.     

Reproductive and general lifestyle determinants of age at menopause.

Determinants of age at menopause were evaluated using data of control subjects collected in the framework of a case-control study on breast and female genital tract neoplasms. After exclusion of women with surgical or pharmacological menopause, a total of 863 post-menopausal women aged 55-74 years admitted to a network of general and university hospitals for non-neoplastic, non-gynecological, non-endocrine-related acute conditions were considered for this analysis. No relationship emerged between cohort of birth, marital status and mean age at menopause. No association was observed with education, but women with 12 years of schooling or more reported a slightly later mean age at menopause (50.2 years vs. 49.3 for < 7 years of schooling). There was a strong, statistically significant association with smoking, mean age at menopause being more than 1 year earlier in ever-smokers than in never-smokers. Nulliparous women tended to report an earlier age at menopause (49.0 years) than parous ones (49.5) and mean age at menopause rose with number of births, being 49.8 in women reporting three or more births. This trend was of borderline statistical significance. No association emerged between age at menopause and number of spontaneous abortions, lifelong menstrual pattern and age at menopause. The significant association between smoking, parity and age at menopause observed in the univariate analysis was confirmed after taking into account the potential confounding effects of age and education in multivariate analysis.     

The protective role of trait anxiety: a longitudinal cohort study

BACKGROUND: Most research has indicated that neuroticism (or trait anxiety) is associated with only negative outcomes. Such a common, heritable and variable trait is expected to have beneficial as well as detrimental effects. We tested the hypothesis that trait anxiety in childhood reduces the risk of dying from accidental causes in early adult life. METHOD: A longitudinal, population-based, birth cohort study of 4,070 men and women born in the UK in 1946. Trait anxiety as judged by teachers when the participants were 13 and 15 years old, and the neuroticism scale of a Maudsley Personality Inventory (MPI) when the participants were 16 years old. Outcomes were deaths, deaths from accidents, non-fatal accidents, and non-fatal accidents requiring medical intervention. RESULTS: Adolescents with low trait anxiety had higher rates of accident mortality to age 25 [low anxiety at 13, hazard ratio (HR) 5.9, low anxiety at 15, HR 1.8]. Low trait anxiety in adolescence was associated with decreased non-accidental mortality after age 25 (low anxiety at 13, HR 0; low anxiety at 15, HR 0.7; low neuroticism at 16, HR 0.7). CONCLUSIONS: High trait anxiety measured in adolescence is associated with reduced accidents and accidental death in early adulthood but higher rates of non-accidental mortality in later life.     

Menarcheal age in Turkey: Secular trend and socio-demographic correlates

Background: Menarche is an important indicator for assessing the developmental status of pubertal girls. Despite its importance, there is no nationwide information on menarcheal age in Turkey.

Aim: This paper is the first attempt to examine age at menarche for Turkey as a whole. The aim is to present the secular trend of menarcheal age and variations across different socio-demographic groups.

Methods: Data were employed from the Turkey Demographic and Health Survey, 2008. Mean menarcheal ages were estimated for birth cohorts and socio-demographic sub-groups. The pace of decline in menarcheal age has been estimated using multiple linear regression analysis, controlling for year of birth and other variables.

Results: Mean age at menarche was estimated as 13.30 (95% CI = 13.26–13.35). It was estimated as 13.17 years (95% CI 12.95–13.38) for the youngest birth cohort (1989–1993), as opposed to 13.44 (95% CI 13.37–13.52) years for the cohort born in 1959–1968.

Conclusion: Regression analysis indicated a decrease of 1.44 months per decade, providing evidence of a secular trend in menarcheal age in Turkey. Further results suggested childhood place of residence, education, welfare status and number of siblings to be significantly associated with menarcheal age.     

Major depression and cigarette smoking: results of a 21-year longitudinal study

BACKGROUND: The aim of this paper was to examine the association between major depression and cigarette smoking among young adults in a birth cohort before and after adjusting for confounding factors. METHOD: Data were gathered over the course of the Christchurch Health and Development Study (CHDS). The CHDS is a longitudinal study of a birth cohort of 1265 New Zealand children studied to age 21. Data were gathered by interview on: (a) major depression over the period 16-21 years; (h) daily smoking and nicotine dependence over the period from 16-21 years. In addition, the study included extensive information on social, family, and behavioural factors in childhood and adolescence. RESULTS: Young people meeting DSM-IV criteria for major depression had elevated rates of daily smoking and nicotine dependence. These associations were reduced substantially by control for potential confounding child and adolescent factors. Nonetheless, even after such control, major depression was associated with increased rates of daily smoking (IRR = 1.19; 95% CI = 1.03, 1.39) and elevated rates of nicotine dependence (OR = 1.75; 95% CI = 1.13, 2.70). CONCLUSIONS: The results suggest that much of the association between smoking and depression reflects common confounding factors that are associated with both outcomes. Nonetheless, even after control for these factors there is evidence of a possible causal linkage between smoking and depression. The direction of causality between smoking and depression remains unknown.     

Breast cancer in relation to childhood parental divorce and early adult psychiatric disorder in a British birth cohort

BACKGROUND: Jacobs and Bovasso reported (Psychological Medicine 2000, 30, 669-678) that maternal death in childhood and chronic severe depression in adulthood were associated with subsequent breast cancer. We have examined the effects of parental loss in childhood and psychiatric disorder in adult life on breast cancer risk using a national birth cohort study. METHOD: Eighty-three cases of breast cancer were diagnosed in a study of 2253 women followed from birth to age 59 years. Cox proportional hazards models were used to test whether breast cancer rates were higher in women who experienced parental death and divorce before age 16, psychiatric disorders between 15 and 32 years, symptoms of anxiety and depression at 36 years, or use of antidepressant medication at 31 or 36 years than in women who did not have these experiences. RESULTS: There was no overall association between parental death, parental divorce or psychiatric disorder and the incidence of breast cancer. There was some evidence that women with more severe psychiatric disorders between the ages of 15 and 32 years were more likely to develop breast cancer early. The interaction between parental divorce and severe psychiatric disorder was non-significant (p=0.1); however, the group who experienced both these events had an increased breast cancer risk compared with those who experienced neither [hazard ratio (HR) 2.64, 95% confidence interval (CI) 1.13-6.19]. CONCLUSIONS: Our study does not provide strong support for the hypothesis that early loss or adult psychiatric disorders are associated with breast cancer. A meta-analysis is needed that uses data from all available cohort studies and investigates possible interactive effects on breast cancer risk.