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Job stress and breast cancer risk: the nurses' health study.

Workers tend to perceive certain features of their jobs as harmful to health and are alert to associations between job stress and health outcomes, but few observational studies have evaluated the role of job stress in carcinogenesis. The authors prospectively assessed the association between job strain, measured by Karasek and Theorell's job content questionnaire in four categories (low strain, active, passive, and high strain), and breast cancer risk among participants in the Nurses' Health Study. A total of 37,562 US female registered nurses were followed for up to 8 years (1992-2000), and 1,030 cases of invasive breast cancer were ascertained during that period. All participants were still in the workforce at baseline and completed the job content questionnaire. Adjusted for age, reproductive history, and other breast cancer risk factors, the multivariate relative risks of breast cancer, in comparison with women who worked in low-strain jobs, were 0.83 (95% confidence interval (CI): 0.69, 0.99) for women in active jobs, 0.87 (95% CI: 0.73, 1.04) for women in high-strain jobs, and 0.90 (95% CI: 0.76, 1.06) for women in passive jobs. Findings from this study indicate that job stress is not related to any increase in breast cancer risk.

Adult↗

Maternal recall of breastfeeding duration by elderly women.

Studies of long-term effects of breastfeeding on the health of both infants and mothers often rely on maternal recall of breastfeeding duration after several decades. The authors evaluated this recall by 140 college-educated, US women 69-79 years of age who breastfed a child in 1940-1956 and recorded the duration both prospectively in a diary for the Menstruation and Reproductive History Study and retrospectively in a questionnaire in 1990-1991. Mean prospective breastfeeding duration was 5.6 months (range, 1-12 months). Mean reporting difference, questionnaire minus diary duration, was 0.0 months, with a standard deviation of 2.7 months; women who recorded short durations tended to overreport, while women who noted long durations underreported. The weighted kappa statistic for reporting agreement was 0.55 (95% confidence interval: 0.42, 0.67), with better recall observed for women in the youngest quintile at recall, firstborns, and infants with more siblings. Ever having breastfed was recalled by 94% of women. For categories of 1-3, 4-6, 7-9, and 10-12 months, recalled breastfeeding duration was correctly classified by 54% of women and was classified within +/-1 category by 89%. The observed misclassification, if nondifferential with respect to outcome, would appreciably attenuate estimates of dose-response associations between breastfeeding duration and later health.

Aged↗

Adult-onset vulvodynia in relation to childhood violence victimization.

Researchers have failed to find a consistent association between childhood victimization and vulvodynia, a debilitating, unexplained vulvar pain condition. However, selection bias associated with case ascertainment, and differential reporting bias between clinic-based cases and controls, may explain in part the inconsistent findings. In 2000-2003, the authors identified 125 women experiencing symptoms of vulvar pain consistent with vulvodynia and 125 age- and community-matched controls from the Boston, Massachusetts-area general population. Telephone-administered questionnaires were used to obtain medical, psychiatric, and reproductive histories. Self-administered surveys assessed childhood exposure (age <12 years) to physical and sexual abuse and to poor family support. After author adjustment for socioeconomic position, women with vulvar pain versus controls were 2.6 times more likely to report never/rarely receiving childhood family support, such as comfort, encouragement, and love (95% confidence interval (CI): 1.3, 5.1). Adult-onset vulvodynia was strongly associated with abuse as a child more than a few times physically (odds ratio (OR) = 4.1, 95% CI: 1.7, 10.0) or sexually (OR = 6.5, 95% CI: 1.2, 35.1). When abused women were compared with those with no history of abuse, the association was largely confined to those harmed by a primary family member (OR = 3.6, 95% CI: 1.6, 8.0 for physical abuse; OR = 4.4, 95% CI: 0.9, 22.9 for sexual abuse). Additional population-based studies of clinically confirmed cases of vulvodynia are needed to replicate this association.

Adult↗

Pregnancy outcomes, infant mortality, and arsenic in drinking water in West Bengal, India.

Between 2001 and 2003, the authors studied pregnancy outcomes and infant mortality among 202 married women in West Bengal, India. Reproductive histories were ascertained using structured interviews. Arsenic exposure during each pregnancy, including all water sources used, was assessed; this involved measurements from 409 wells. Odds ratios for spontaneous abortion, stillbirth, neonatal mortality, and infant mortality were estimated with logistic regression based on the method of generalized estimating equations. Exposure to high concentrations of arsenic (> or =200 microg/liter) during pregnancy was associated with a sixfold increased risk of stillbirth after adjustment for potential confounders (odds ratio (OR) = 6.07, 95% confidence interval (CI): 1.54, 24.0; p = 0.01). Arsenic-related skin lesions were found in 12 women who had a substantially increased risk of stillbirth (OR = 13.1, 95% CI: 3.17, 54.0; p = 0.002). The odds ratio for neonatal death was 2.81 (95% CI: 0.73, 10.8). No association was found between arsenic exposure and spontaneous abortion (OR = 1.01, 95% CI: 0.38, 2.70) or overall infant mortality (OR = 1.33, 95% CI: 0.43, 4.04). This study adds to the limited evidence that exposure to high concentrations of arsenic during pregnancy increases the risk of stillbirth. However, there was no indication of the increased rates of spontaneous abortion and overall infant mortality that have been reported in some studies.

Arsenic Poisoning↗

The Inter-Regional, Epidemiological Study of Childhood Cancer (IRESCC): case-control study in children with germ cell tumours.

In 1980-1983 members of IRESCC interviewed parents of 555 children with newly diagnosed cancer on topics of possible aetiological significance. Identical questions were asked of the parents of 1100 control children chosen from hospital admissions and general practitioner lists. Medical information was confirmed whenever possible by cross-checking with NHS records. Data for the 41 children with germ cell tumours and their 82 controls are reported here. The cases had more major congenital malformations than controls, including one neural tube defect. More case than control mothers and fathers reported occupational exposure to chemicals. Nine close relatives of cases had multiple primary tumours, which were often benign or of low-grade malignancy, compared with 1 hospital control and 3 general practitioner control relatives. Cases and controls differed with respect to birth weight and paternal age. No case-control differences were shown for: birth rank, maternal age, chronic illnesses and smoking, mothers' reproductive histories and oral contraceptive usage. In index pregnancies there were no case-control differences for maternal illness, infections, alcohol intake and X-ray and ultrasound exposure. There was no difference between cases and controls for the frequency of twinning the families.

Adolescent↗

The relationship of menopausal hot flushes to medical and reproductive experience.

Information regarding the relationship of menopausal hot flushes to menstrual, reproductive and clinical events were obtained from women participating in a case-control study of breast cancer risk. Naturally menopausal women who reported the occurrence of menopausal hot flushes were compared with those without such complaints in an attempt to identify factors that might predict the occurrence of menopausal symptoms. Two-thirds of the women reported such symptoms. The symptomatic and asymptomatic groups did not differ in body weight, suggesting that extraglandular estrogen production in obese women does not protect against occurrence of menopausal symptoms. Neither past medical nor reproductive history were predictive of the occurrence of hot flushes. Women with hot flushes more commonly reported the occurrence of menstrual cycle variability and of long menstrual cycles during the 5 years before menopause. Since perimenopausal cycle variability probably reflects the irregular maturation of residual ovarian follicles accompanied by elevated gonadotropin concentrations, symptomatic women may have earlier activation of the neuroendocrine mechanism that has been associated with both pulsatile gonadotropin release and the hot flush.

Adolescent↗

Life after infertility treatment: a long-term investigation of marital and sexual function.

After leaving in-vitro fertilization (IVF) treatment, both successful and unsuccessful women are generally lost to follow-up. In order to assess overall life satisfaction as well as marital and sexual adjustment after the completion of infertility treatment, three groups of women were studied: group 1 (n = 41), successful IVF women; group 2 (n = 16), unsuccessful IVF women who adopted; and group 3 (n = 18), unsuccessful IVF women who remained childless. All women who had completed a minimum of three IVF cycles between the years 1982 and 1993 were invited to participate in a 'life after infertility' follow-up study. Those who agreed were mailed a lengthy questionnaire which included questions about their reproductive history and infertility treatment, the impact of infertility on their marital and sexual relationship and their final thoughts about treatment. Four standardized questionnaires were also administered. Results revealed that women who became biological mothers through IVF were significantly more satisfied with their lives than women who were unsuccessful in IVF and remained childless (F = 8.62, P < 0.001). Childless women reported that infertility had exerted a significantly greater negative impact on their marriages than that reported by the other two groups. There were no significant differences, however, between the three groups on the standardized measures of marital and sexual satisfaction.

Female↗

Y chromosome microdeletion in a father and his four infertile sons.

Microdeletions of Yq are associated with azoospermia and severe oligozoospermia. In general, men with deletions are infertile and therefore deletions are not transmitted to sons unless in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are performed. We report an unusual family characterized by multiple members with infertility and Yq microdeletion. Complete reproductive history, semen analyses and blood samples were elicited from relevant family members. DNA preparation and quantification were performed using commercial kits. A total of 27 pairs of sequence tagged sites based primer sets specific for the Y microdeletion region loci were used for screening. Southern blots using deleted in azoospermia (DAZ) and ribosomal binding motif (RBM) cDNAs were then analysed for confirmation. The proband, his three brothers and father were all found to be deleted for DAZ but not RBM. At the time of analysis, the proband's father was azoospermic whereas his four sons were either severely oligozoospermic or azoospermic. Unlike their father, the four sons are infertile and have no offspring, except for one of them who achieved a daughter only after IVF/ICSI treatment for infertility. Microdeletions of Yq involving the DAZ gene are associated with a variable phenotypic expression that can include evidently normal fertility.

Blotting, Southern↗

Sperm analysis by FISH in a case of t(17; 22) (q11; q12) balanced translocation: case report.

Individual sperm from men with balanced translocations have different chromosomal contents. Thus, an estimation of the overall sperm chromosomal imbalance of such patients could help to give the couple an adapted genetic counselling. We report here the study of a balanced translocation carrier, t(17;22) (q11;q12) whose reproductive history reported four miscarriages. Moreover, he had an abnormal semen analysis with oligoteratozoospermia. The meiotic segregation pattern was examined in 700 sperm, using fluorescence in-situ hybridization (FISH). Nineteen percent of the sperm had balanced translocations or were normal. All other sperm were unbalanced (81%) and their distribution was observed as follows: the frequencies of adjacent 1, adjacent 2 and 3:1 segregations were 12.9, 5.8 and 46.8% respectively. Among the segregations scored, 13.7% were related to second meiotic division abnormalities. Less than 2% of the total sperm scored were not explained. The 3:1 segregation was present at a very high rate, which is very unusual. In cases of balanced translocations, we believe that no general features can be drawn. Thus, the FISH technique may be very helpful for genetic counselling, which remains an important step and must be done with care.

Adult↗

Self-reported difficulty in conceiving as a measure of infertility.

BACKGROUND: This study aimed to explore the meaning and potential use of women's self-reported difficulties in conceiving as a measure of infertility in epidemiological studies, and to compare women's stated reasons for infertility with information in their medical records. METHODS: Data were available from a population-based case-control study of ovarian cancer involving 1638 women. The sensitivity and specificity of women's self-reported infertility were calculated against their estimated fertility status based on detailed reproductive histories. Self-reported reasons for infertility were compared with diagnoses documented in women's medical records. RESULTS: The sensitivity of women's self-reported difficulty in conceiving was 66 and 69% respectively when compared with calendar-derived and self-reported times taken trying to conceive; its specificity was 95%. Forty-one (23%) of the 179 women for whom medical records were available had their self-reported fertility problem confirmed. Self-reported infertility causes could be compared with diagnoses in medical records for only 22 of these women. CONCLUSIONS: Self-reported difficulty conceiving is a useful measure of infertility for quantifying the burden of fertility problems experienced in the community. Validation of reasons for infertility is unlikely to be feasible through examination of medical records. Improved education of the public regarding the availability and success rates of infertility treatments is proposed.

Case-Control Studies↗

Association of CYP1A1 gene polymorphism with recurrent pregnancy loss in the South Indian population.

BACKGROUND: We investigated the relationship between idiopathic recurrent pregnancy loss (RPL) and genetic polymorphisms in phase I and phase II detoxification genes which include CYP1A1, CYP2D6, GSTM1, GSTP1 and GSTT1. METHOD: A case-control study comprised 160 females with RPL and 63 healthy controls with a successful reproductive history. RESULTS: The CYP1A1 variant allele was present at frequencies of 0.61 and 0.44 in cases and controls, respectively (odds ratio=1.93; P=0.023, 95% confidence interval 1.10-3.38). The CYP2D6 variant allele was present at a frequency of 0.17 in females with RPL, while in the control population the frequency was 0.16. The GSTM1 and GSTT1 null genotypes were present at frequencies of 0.39 and 0.26 in RPL cases, whereas in controls the frequencies were 0.37 and 0.17, respectively. The mutant GSTP1 frequencies in case and control women were 0.38 and 0.40, respectively. We report a significant association of the CYP1A1*2A allele with RPL which is confirmed by logistic regression analysis. No association was observed for the other polymorphisms or in their combinations studied. CONCLUSIONS: The present study suggests the occurrence of the CYP1A1*2A allele as a probable risk factor in idiopathic recurrent miscarriages.

Abortion, Habitual↗

Fecundability according to male serum inhibin B--a prospective study among first pregnancy planners.

BACKGROUND: New biological markers of male fecundity are needed for use in large-scale epidemiological studies. We studied the association between male inhibin B and fecundability. METHODS: Four hundred and thirty Danish couples without previous reproductive experience were followed from termination of contraception until pregnancy or for a maximum of six menstrual cycles. At enrolment we obtained semen samples (n = 418) and blood samples to measure reproductive hormones, including inhibin B (n = 343). RESULTS: The fecundability odds ratio for an increment of male inhibin B by 1 log pg/ml was 1.428 (95% confidence interval 1.022-1.994), adjusted for factors influencing the crude estimate. Only inhibin B values below 100 pg/ml were strongly related to fecundability. We designed a receiver operating characteristic curve based on the 29 males with serum inhibin B #100 pg/ml. The area under the curve (AUC) for inhibin B was 0.787 and the corresponding AUCs for sperm density and FSH were 0.913 and 0.800, respectively. CONCLUSION: Serum inhibin B may be a reliable marker of male fecundity for epidemiological research and may have some advantages over sperm density. Our findings do not support the replacement of sperm density by male inhibin B when obtaining sperm data is an option.

Adult↗

The miscarriage-associated HLA-G -725G allele influences transcription rates in JEG-3 cells.

BACKGROUND: HLA-G is a non-classical HLA with important immunomodulatory roles in pregnancy. A polymorphism in the promoter region, -725G, was previously associated with sporadic miscarriage in women who were unselected with respect to reproductive history. In this study, the transcription levels of different HLA-G promoter haplotypes were examined to determine whether the miscarriage-associated -725G allele influences transcription. METHODS: Five naturally occurring promoter haplotypes and three variant haplotypes created by site-directed mutagenesis were sub-cloned into luciferase expression vectors and transfected into JEG-3 cells. Expression levels of these eight haplotypes were examined in cultured cells before and after treatment with interferon-beta (IFN-beta), cytosine-5-DNA methyltransferase (M. SssI) and 5-aza-2'-deoxycytidine. Differences in expression levels between haplotypes were determined by analysis of variance (ANOVA). RESULT: Promoter haplotypes with the miscarriage-associated -725G allele were expressed at significantly higher levels in all culture conditions compared with otherwise identical haplotypes that had a -725C or -725T allele. CONCLUSION: Variation in the HLA-G promoter region influences transcription rates. Contrary to expectations, increased expression of HLA-G may be disadvantageous in some pregnancies.

Abortion, Spontaneous↗

Prevalence and socioeconomic correlates of subfecundity and spontaneous abortion in Denmark.

This paper provides an estimate of the prevalence of subfecundity and spontaneous abortion in Denmark, and examines social factors associated with these problems of reproduction. The data of this study were collected by interviewing a stratified random sample of 1.4 women per thousand in Denmark between the ages 25 and 45. The interview generated detailed information on reproductive history and sociodemographic data for 709 women. The survey results indicate that reduced fecundity is a relatively common health problem. The proportion of women that either could not achieve a wanted conception or experienced a delay of one or more years before achieving conception was 0.16 in a first pregnancy and 0.17 in a second or subsequent pregnancy attempt. Four per cent of the women interviewed never produced a desired first child and an additional four per cent reported failure to produce a second or subsequent desired child. Social factors relating to subfecundity and spontaneous abortion were studied using logistic regression. No significant associations were found between the occurrence of subfecundity and family net income, employment status of the 'head of the household', area of residence, type of housing or age at time of interview. Women without a college education were more likely to exhibit primary subfecundity than college-educated women (p less than .05). The rate of spontaneous abortion was not found to be associated with socioeconomic class. A significantly higher rate of abortion was found among women with a history of subfecundity than among women with no such history.

Abortion, Incomplete↗

The influence of secular effects and gravidity on the rate of ectopic pregnancy in a Norwegian population.

In order to assess the influence of secular effects and gravidity on the incidence rate of ectopic pregnancy, information from reproductive history questionnaires was obtained for 7804 gravid females identified through the Norwegian Twin Panel. The overall ectopic pregnancy incidence rate was 5.6 per 1000 estimated conceptions, with rates increasing for women born after 1950. Women experiencing their first pregnancy were at lowest risk for that pregnancy being ectopic. When women were stratified by whether they were born before or after 1950, gravidity still had an effect on the incidence rate of ectopic pregnancy. Conversely, year of birth was influential when stratifying by gravidity. The results obtained here suggest that the recent increase in the incidence of ectopic pregnancy is unrelated to the number of prior pregnancies.

Diseases in Twins↗

Oral contraceptive use and premenopausal breast cancer in Sweden and Norway: possible effects of different pattern of use.

Different use of oral contraceptives (OCs) in relation to reproductive histories and age might explain the conflicting results found in studies from different countries of OC use and premenopausal breast cancer. A population-based case-control study in Sweden and Norway has been analysed separately for the two countries. The study consists of 317 Swedish and 105 Norwegian cases diagnosed 1984-1985 with 317 Swedish and 210 Norwegian controls. The results for each country separately are consistent with the joint analysis showing increased risk for breast cancer with increased duration of OC use with the exception of that for women with more than 15 years since first use. The relative risk of breast cancer for more than four years of use among Norwegian women was 0.6 (95% confidence internal (Cl), 0.2-1.8). In both countries there was a non-significant higher risk associated with increasing duration of use before first full-term pregnancy. Analyses for surveillance bias show no evidence of bias as explanation for the association between total duration of OC use and breast cancer.

Adult↗

Maternal and gestational factors in cryptorchidism.

Previous epidemiological studies of cryptorchidism have led to the hypothesis that the risk of undescended testis is associated with excess oestrogen exposure during pregnancy. A case-control study was undertaken to test this hypothesis, comparing mothers of affected boys (244) and normal male births (488) born within six months of a case selected randomly from the British Columbia population. Information was collected on the mother's reproductive history, family history, and past medical history, and events surrounding all pregnancies ending in a birth. The results were analysed using both the population-based sample of male births and the male sibs of cases as control groups. Neither exogenous oestrogen exposure, nor any of the pregnancy-related variables hypothesized to be indirect indicators of endogenous oestrogen exposure, including bleeding and nausea and/or vomiting, were found to be significantly associated with risk of undescended testes in either comparison. More mothers with later index births reported menstrual irregularity greater than half the time, and smoking, thought to have a protective effect, was more prevalent among case mothers than control mothers. No other variables were significantly different between case and control mothers. The results of this study do not support the hypothesis that elevated exogenous or endogenous oestrogen exposure during pregnancy increases the risk of undescended testis in male children.

Body Weight↗

Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes. A prospective cohort study.

BACKGROUND: Most studies of the reproductive consequences of cigarette smoking base exposure on self-reported smoking habits. This study examines the relationship of birth outcomes to the timing and intensity of maternal active and passive smoking estimated both from self-reports and from cotinine concentration in maternal urine during early, middle, and late gestation. METHOD: This cohort study included 740 white and Hispanic women who obtained antenatal care at the East Boston Neighborhood Health Center between 1986 and 1992. At each antenatal visit, information on maternal active and passive smoking was obtained by a detailed questionnaire, and by measurement of urine cotinine concentrations. Infant birth outcomes were obtained from hospital records. Multiple linear regression was used to evaluate antenatal smoking variables on birth outcomes, with adjustment for maternal demographic characteristics, reproductive history, alcohol use, maternal weight and height, and infant gender. RESULTS: The percentage of mothers who ever smoked cigarettes during pregnancy was 55.5% for white and 10.2% for Hispanic women. A significant inverse exposure-response relationship between cotinine concentration in maternal urine and infant size at birth was demonstrated. However, the relationship was less clear between maternal self-reported smoking status and these outcomes. For the entire gestation, a 1000 ng increase in mean urine cotinine concentration was associated with a 59 +/- 9 g reduction in birthweight, a 0.25 +/- 0.05 cm reduction in length, and a 0.12 +/- 0.03 cm reduction in head circumference, respectively. For maternal passive smoking, the much smaller magnitude of effect precludes firm conclusions. CONCLUSIONS: These data suggest that preventing and reducing active maternal smoking during pregnancy may have a beneficial impact on infant size at birth.

Adult↗