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Biomedical subjects

H Kolstad

Publications and source records attributed to H Kolstad.

At least 19 recordsLinked to original sources

Adult and prenatal exposures to tobacco smoke as risk indicators of fertility among 430 Danish couples.

During 1992-1995, 430 Danish couples were recruited after a nationwide mailing of a letter to 52,255 trade union members who were 20-35 years old, lived with a partner, and had no children. The couples were enrolled into the study when they discontinued birth control, and they were followed for six menstrual cycles or until a clinically recognized pregnancy. At enrollment and each month throughout the follow-up, both partners completed a questionnaire that asked them about their smoking, alcohol consumption, and intake of caffeinated beverages. The effect of current smoking and smoking exposure in utero was evaluated by using a logistic regression model with pregnancy outcome of each cycle in a Cox discrete model calculating the fecundability odds ratio. After adjustment for female body mass index and alcohol intake, diseases in female reproductive organs, semen quality, and duration of menstrual cycle, the fecundability odds ratio for smoking women exposed in utero was 0.53 (95% confidence interval (CI) 0.31-0.91) compared with unexposed nonsmokers. Fecundability odds ratio for nonsmoking women exposed in utero was 0.70 (95% CI 0.48-1.03) and that for female smokers not exposed in utero was 0.67 (95% CI 0.42-1.06). Exposure in utero was also associated with a decreased fecundability odds ratio in males (0.68, 95% CI 0.48-0.97), whereas present smoking did not reduce fecundability significantly. It seems advisable to encourage smoking cessation prior to the attempt to conceive as well as during pregnancy.

Adolescent↗

Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners.

BACKGROUND: Semen analysis is part of the routine assessment of infertile couples. WHO defines a sperm concentration above 20x10(6) per mL seminal fluid as normal. We studied the association between semen quality and the probability of conception in a single menstrual cycle in Danish couples with no previous reproductive experience. METHODS: In 1992-94, we invited 52,255 trades-union members aged 20-35 years, who lived with a partner and had no children to take part in the study; 430 couples agreed. The couples discontinued use of contraception, and were followed up for six menstrual cycles or until a pregnancy was verified within this period. Each man was asked to provide a semen sample at enrolment (which was analysed without freezing). Women kept a daily record of vaginal bleeding and sexual activity. The association between semen quality and likelihood of pregnancy was assessed by logistic regression, adjusted for sexual activity and female factors associated with low fertility. RESULTS: There were 256 (59.5%) pregnancies among the 430 couples: 165 (65.0%) among those with a sperm concentration of 40x10(6)/mL or more and 84 (51.2%) among those with lower sperm concentrations. The probability of conception increased with increasing sperm concentration up to 40x10(6)/mL, but any higher sperm density was not associated with additional likelihood of pregnancy. The proportion of sperm with normal morphology was strongly related to likelihood of pregnancy independently of sperm concentration. Semen volume and motility were of limited value in pregnancy prediction. INTERPRETATION: Our study suggests that the current WHO guidelines for normal semen quality should be used with caution. Some men with sperm counts above the lower limit of the normal range defined by WHO may in fact be subfertile.

Adult↗

Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy.

OBJECTIVE: To examine the effect of alcohol consumption on the probability of conception. DESIGN: A follow up study over six menstrual cycles or until a clinically recognised pregnancy occurred after discontinuation of contraception. SUBJECTS: 430 Danish couples aged 20-35 years trying to conceive for the first time. MAIN OUTCOME MEASURES: Clinically recognised pregnancy. Fecundability odds ratio: odds of conception among exposed couples divided by odds among those not exposed. RESULTS: In the six cycles of follow up 64% (179) of women with a weekly alcohol intake of less than five drinks and 55% (75) of women with a higher intake conceived. After adjustment for cycle number, smoking in either partner or smoking exposure in utero, centre of enrolment, diseases in female reproductive organs, woman's body mass index, sperm concentration, and duration of menstrual cycle, the odds ratio decreased with increasing alcohol intake from 0.61 (95% confidence interval 0.40 to 0.93) among women consuming 1-5 drinks a week to 0.34 (0.22 to 0.52) among women consuming more than 10 drinks a week (P=0.03 for trend) compared with women with no alcohol intake. Among men no dose-response association was found after control for confounders including women's alcohol intake. CONCLUSION: A woman's alcohol intake is associated with decreased fecundability even among women with a weekly alcohol intake corresponding to five or fewer drinks. This finding needs further corroboration, but it seems reasonable to encourage women to avoid intake of alcohol when they are trying to become pregnant.

Adult↗

Mortality of short-term workers in two international cohorts.

The purpose of this study was to compare the pattern of mortality of blue-collar workers employed less and more than 1 year in the man-made vitreous fiber (MMVF) and the reinforced plastic industries, the latter group being exposed to styrene. We conducted an analysis among 21,784 workers with less than 1 year of employment (short-term workers) and 19,117 workers with 1 or more years of employment (long-term workers) employed in eight European countries. We conducted analyses based on external as well as internal comparisons. In both cohorts, the standardized mortality ratio for all causes among short-term workers was approximately 40% higher, compared with that for longer-term workers. In internal comparisons, the difference was reduced to 9% in the MMVF cohort and 11% in the styrene cohort. Workers with less than 1 month of employment displayed an increased mortality in both cohorts and in most countries. The increased mortality among short-term workers was not concentrated shortly after they quit employment. In both cohorts, short-term workers had a higher mortality from external causes, while little difference was seen in mortality from ischemic heart disease and malignant neoplasms. Although extra-occupational factors may contribute to increase the mortality of short-term workers and, in particular, of those employed for less than 1 month, the difference observed in analyses adjusted for characteristics of employment suggested a relatively small difference in mortality from most causes.

Adult↗

Fertility of Danish battery workers exposed to lead.

BACKGROUND: Inorganic lead may impair male fecundity through its action on the germinal epithelium, the endocrine system or both, but information on possible impact on fertility in exposed populations is limited. METHODS: Fertility was examined in 1349 male battery plant employees and in 9596 reference company employees over a follow-up of 25,949 and 183,414 person years respectively. The cohorts were identified by records in a national pension fund and information on births was obtained from the Danish Population Register. In a subset of the battery worker cohort, the average level of lead in blood was 35.9 micrograms/dl (4639 blood samples on 1654 person years in 400 workers; SD 13.0; range 3-125). The birth rate was analysed by logistic regression on occupational exposure and several extraneous determinants (age, parity, calendar year, and previous children). RESULTS: The birth-rate was not reduced in years at risk from exposure to lead in comparison with years not-at-risk; either in comparison with not-at-risk years within the battery plant cohort (odds ratio [OR] = 0.997, 95% confidence interval [CI]: 0.88-1.13), or in comparison with the external reference population (OR = 0.983, 95% CI: 0.87-1.11). CONCLUSIONS: Inorganic lead seems not to impair fertility among Danish battery workers. This finding does not rule out that the time taken to achieve a pregnancy is increased among battery workers because most pregnancies in Denmark are planned.

Adult↗

Inhibin B as a serum marker of spermatogenesis: correlation to differences in sperm concentration and follicle-stimulating hormone levels. A study of 349 Danish men.

Recent studies have focused on reproductive health of men in the general population. However, semen samples are difficult to obtain within sampling frames that allow comparisons. Blood samples are easier to obtain than ejaculates. Therefore, serum biomarkers of spermatogenesis are of major interest for population studies. FSH has previously been used as a marker of spermatogenesis, although it is also influenced by the hypothalamus. Serum inhibin B was recently suggested as a possible, more direct serum marker of spermatogenesis in men with testicular disorders. In a Danish nationwide collaborative study, we found an unexpected difference in semen concentration between two groups of men recruited from two different centres. We, therefore, analyzed reproductive hormones in blood, including inhibin B, to test whether the observed difference in semen concentration was reflected in the reproductive hormones. From 1992 to 1995, a total of 430 men, 20-35 yr old, who lived with a partner and who had not previously attempted to achieve a pregnancy, were recruited. The couples were enrolled into the study in one of two centres (centre A, n = 231; and centre B, n = 199) when they discontinued birth control. At enrollment, they provided a semen sample (n = 419), and a blood sample was drawn (n = 349). The semen analysis was performed in accordance with the WHO 1992 guidelines, and interlaboratory differences were tested. Inhibin B was measured in an enzyme immunometric assay, which has previously been described. All blood samples were analyzed in the same laboratory. Median sperm concentration and the percentage of morphologically normal spermatozoa were significantly higher among men from centre A (56.0 mill/mL and 42.5%), compared with men from centre B (44.8 mill/mL and 39%). Men from centre B had a significantly higher median FSH (3.42 IU/L) and a lower inhibin B (186 pg/mL) than men from centre A (3.21 IU/L and 209 pg/mL). The differences persisted after control for potentially confounding variables. A significant correlation was found between the cubic root-transformed serum FSH and inhibin B levels (r = -0.61, P < 0.001), between the cubic root-transformed serum FSH and sperm concentration (r = -0.40, P < 0.001), and between the cubic root-transformed inhibin B and sperm concentration (r = 0.38, P < 0.001). The predictive power of detecting sperm counts below 20 mill/mL among men who's inhibin B and FSH both were below 80 pg/mL and above 10 IU/L, respectively, was 100%. The unexpected significant difference in semen concentration between two groups of normal Danish men was probably caused by differences in sampling procedures in the two centres where the men were recruited, rather than geographical differences. However, similar differences in serum levels of inhibin B and FSH between centres were found. These findings suggest that a real difference in spermatogenic potential between the two groups of men existed. We suggest that serum inhibin B, in future population studies on male reproductive health, may serve as a new marker of spermatogenesis, in addition to sperm concentration and serum FSH.

Adult↗

Exposure to styrene and mortality from nervous system diseases and mental disorders.

Chronic low-dose exposure to solvents has been associated in epidemiologic studies with chronic neurotoxicity, but the evidence is not consistent. Styrene causes acute disturbances in the central and peripheral nervous systems. To determine if exposure to styrene may contribute to chronic diseases of the central nervous system, the authors examined mortality from nervous system diseases, mental disorders, and suicide in relation to styrene exposure in an international historical cohort study. The cohort involved 35,443 workers employed during 1945-1991 in the reinforced plastics industry, where high exposures to styrene occur. Indicators of exposure were reconstructed through job histories and environmental and biologic monitoring data. Poisson regression was used for internal comparisons. Mortality from diseases of the central nervous system (27 deaths) increased with time since first exposure, duration of exposure, average level of exposure, and cumulative exposure to styrene. A quadratic model described best the dose-response shape for cumulative exposure and duration of exposure with the highest risks at around 300 ppm-years and 5 years, respectively, and a subsequent decrease in risk in the highest exposure categories. Mortality from epilepsy increased monotonically with all styrene exposure indicators, while associations for degenerative diseases of the central nervous system were generally weaker. Mortality from mental disorders and suicide decreased with increasing duration of exposure and cumulative exposure, while there was no trend with time since first exposure and average exposure to styrene. These findings suggest that, in addition to the known acute effects, exposure to styrene may contribute to chronic diseases of the central nervous system.

Cause of Death↗

Exposure to styrene and mortality from nonmalignant respiratory diseases.

A cohort of 34,560 men and 6128 women employed in 660 European factories manufacturing reinforced plastic products, followed up originally to assess the risk of cancer, was used to assess the risk of non-malignant respiratory diseases associated with exposure to styrene. Mortality from pneumonia was associated with intensity of exposure to styrene, but this may have been due to chance. Mortality from bronchitis, emphysema, and asthma was not associated with styrene exposure.

Cohort Studies↗

Exposure to styrene and mortality from nonmalignant diseases of the genitourinary system.

OBJECTIVES: A historical cohort study was carried out to investigate mortality from nonmalignant diseases of the genitourinary system among workers in the reinforced plastics industry, where high workroom concentrations of styrene are encountered. METHODS: The external comparisons in this report were based on an average of 12.6 years of retrospective follow-up of 35 443 workers who were first employed in the reinforced plastics industry during 1945-1991 and were known to have been exposed to styrene in their work. For the internal comparisons, 2641 subjects with incomplete occupational histories were excluded, leaving 32 802 subjects. Previous individual exposure histories to styrene were reconstructed through job histories and environmental and biological monitoring data. RESULTS: Mortality from nonmalignant diseases of the genitourinary system (N = 20) was associated with average exposure to styrene (P for trend 0.05). Weaker increasing trends in risk were seen for time since first exposure and cumulative exposure, while no increase was identified for duration of exposure. There was a significant increasing trend in mortality from nephritis and nephrosis (N = 5), associated with an increasing average level of exposure to styrene (P for trend 0.03). No clear trend was observed for time since first exposure, duration of exposure, or cumulative exposure. CONCLUSIONS: In this large cohort study of workers exposed to styrene, mortality from nonmalignant diseases of the genitourinary system increased as the average intensity of exposure increased. This finding indicates that other data should be scrutinized.

Air Pollutants, Occupational↗

Cancer mortality in a historical cohort study of workers exposed to styrene.

OBJECTIVES: The goal of this study was to determine whether exposure to styrene is associated with an increased risk for neoplasms of the lymphatic and hematopoietic tissues. METHODS: A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden, and the United Kingdom. It involved 40,688 workers ever employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories and environmental and biological monitoring data. Cause-specific national death rates were used as the reference. Poisson regression was applied for internal comparisons. RESULTS: Among the exposed workers, no excess was observed for mortality from all neoplasms. Mortality from neoplasms of the lymphatic and hematopoietic tissues increased with time since first exposure and average level of exposure to styrene, but was not consistently associated with duration of exposure or with cumulative exposure. CONCLUSIONS: These findings leave open the possibility of an excess risk of neoplasms of the lymphatic and hematopoietic tissues among workers exposed to styrene.

Cohort Studies↗

Cancer mortality in an international cohort of workers exposed to styrene.

Increased risks for leukaemia and lymphoma have been suggested in studies of workers exposed to styrene in the rubber and plastics industry. A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden and the United Kingdom involving 40,683 workers employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories, environmental and biological monitoring data and production records of the plants in the study. Cause-specific national death rates were used as the reference. Among exposed workers, no excess was observed for mortality from all causes (2195 deaths, standardized mortality ratio [SMR], 95; 95% confidence interval [CI], 91-99), from all neoplasms, from lung cancer or from other major epithelial cancers. Mortality from neoplasms of the lymphatic and haematopoietic tissues was not elevated (50 deaths; SMR, 96; CI, 71-126) and was not consistently associated with length of exposure. The rate of mortality from leukaemias and lymphomas increased with time since first exposure. Among subjects who had been exposed for more than one year, a two-fold risk was observed 20 years after first exposure (eight deaths; SMR, 197; CI, 85-387). These results are inadequate to exclude the possibility that styrene causes leukaemia and lymphoma.

Cohort Studies↗

Survival of Danish cancer patients 1943-1987. Digestive organs.

Cancers of the digestive organs and peritoneum constituted 28% of all cancers in Denmark in 1943-87. The lack of a common trend in incidence rates for the different tumour types indicates different aetiologies. Survival is worst for cancer of the oesophagus and improves gradually for cancer of the stomach, cancer of the small intestine and colorectal cancers. Survival from these tumours differ little between the sexes, but females have a slightly more favourable prognosis, which is most pronounced for sites with the best survival. The changes in survival over the study period, 1943-87, show virtually no change in the prognosis for oesophageal cancer, very slight, if any, improvement in that for stomach cancer, a detectable improvement in survival from cancer of the small intestine and substantial improvements in survival from colorectal cancer. Survival rates after colorectal cancer appear to be lower in Denmark than those seen in the USA. This finding may be due to the exclusion of certain precancerous lesions from the Danish material, which is not possible in US studies. Cancers of the liver, gallbladder and pancreas all carry extremely high mortality rates, with five-year survival rates below 5%, and one-year survival rates below 5% for cancers of the liver and pancreas.

Age Factors↗

Low birthweight, congenital malformations, and spontaneous abortions among dry-cleaning workers in Scandinavia.

With a common study protocol, case-referent studies within cohorts were performed in Denmark, Norway, Sweden, and Finland to study reproductive hazards of women doing dry-cleaning work. Due to national differences not all of the studies could follow exactly the same procedures in data collection, but they were all based on the linkage of cohorts of dry-cleaning and laundry workers to national registers of births and reproductive failures. Summary measures from each study were combined without the data being pooled. The most significant finding was an increased risk of spontaneous abortion among the most exposed women in the Finnish data. This finding was only supported by the results of the other studies to a minor degree, and the combined odds ratio had confidence limits which included unity.

Abortion, Spontaneous↗

A follow-up study of environmental and biologic determinants of fertility among 430 Danish first-pregnancy planners: design and methods.

This paper presents design and methods of a follow-up study of fecundability (defined as the probability of conception during one menstrual cycle) in first-pregnancy planners. We recruited 430 couples by postal letter among 52,255 members of four trade unions. Couples without earlier reproductive experience were enrolled when they discontinued contraception and were followed in six complete menstrual cycles or until a pregnancy was recognized. Data included daily recordings of coitus and menstrual bleeding. Blood, semen, and urine specimens were collected to assess endocrine profile, semen quality, occult embryonal loss, and occupational exposures. Information was obtained about 1661 menstrual cycles (94% of expected). The proportion of couples obtaining a clinical pregnancy during 6 months of follow-up was 65%, and the average probability to obtain a pregnancy across all cycles was 16% (95% CI 14-18%). Among all conceptions the proportion of early embryonal loss was 17% (95% CI 12-22%). This study demonstrates the feasibility of a prospective study of fertility and that the established study base can provide useful information on environmental risk to subfertility.

Adult↗