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Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown., Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus (T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls., Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively., Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication., Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.

Background: The human androgen receptor (AR) gene contains two polymorphisms of CAG and GGN repeats respectively. The GGN repeat function is still largely unknown and to date there are no in vivo data on this segment with respect to the general population., Methods: We investigated the impact of CAG and GGN repeats on male reproductive function, one by one and in interaction with each other, in 220 adolescent men from the general Swedish population. Physical examination and semen analysis, including accessory sex gland markers and measurement of reproductive hormone levels, were performed. Lifestyle-associated factors, including maternal smoking during pregnancy, were recorded. GGN and CAG repeat lengths were determined by sequencing., Results: GGN<23 was associated with lower semen volume when compared to GGN=23 (mean difference -0.6 ml, P=0.02) and GGN>23 (mean difference -0.9 ml, P=0.002). Men with GGN<23, exposed to maternal smoking during pregnancy, had higher body mass index compared to men with other GGN lengths, no matter whether their mother had smoked or not during pregnancy (mean difference 4.8 kg/m2, P<0.001)., Conclusions: Short GGN repeats seem to be associated with decreased semen volume, possibly due to suboptimal AR activity. Body composition may be influenced by the combination of fetal exposure to maternal smoking and certain AR genotypes.

Background: Both lifestyle factors and occupational and environmental factors have been suggested to affect the female reproductive system. In the present study, the separate and joint effects of several such factors are investigated., Methods: Information on time to pregnancy (TTP) was available for 1578 women randomly selected from the general Swedish population. The information was collected retrospectively by using self-administered questionnaires. By means of logistic regression of survival data, fecundability odds ratios were determined for many factors. Multivariate models were used to determine which factors had the most impact on TTP., Results: Several lifestyle factors were found to associate with TTP. However, only use of oral contraceptives prior to attempting to conceive, menstrual cycle length, age at conception and parity remained in the multivariate models. Together, these factors explained 14% of the variance in TTP. Excluding first and second month conceptions, only age at conception and menstrual cycle length remained in the multivariate models, together explaining only 8% of the variance in TTP., Conclusions: Although information on several factors was available, the multivariate model explained only a small fraction of the variation in the observed time to pregnancies. Furthermore, female biological factors seemed more important predictors of TTP than lifestyle factors.

Background: Persistent organochlorine pollutants (POP) may affect both the female and male reproductive system in animals as well as in humans., Methods: Blood samples were collected from pregnant women and their partners from Greenland, Warsaw and Kharkiv, and from a cohort of Swedish fishermen's wives. Blood samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). Information on the participants' fertility, measured as time to pregnancy (TTP), was collected. In total, 778 men and 1505 women were included in the analyses., Results: The data from Warsaw, Kharkiv and the Swedish fishermen's wives indicated no effect of either male or female exposure to POP on TTP. However, among men and women from Greenland, there seemed to be an association between serum concentrations of CB-153 and p,p'-DDE and prolonged TTP. Due to the strong intra-individual correlation between CB-153 and p,p'-DDE in the Greenlandic population, it was not possible to determine whether the risk was associated with CB-153 or p, p'-DDE or was an interaction between the two compounds., Conclusions: The overall results of the present study create a somewhat ambiguous pattern, but give some support to the idea that dietary POP exposure might be harmful for couple fertility.

Background: Persistent organochlorine pollutants (POP), such as polychlorinated biphenyls (PCB) and dichlorodiphenyldichloroethylene (p, p'-DDE), are widely found in the environment and considered potential endocrine-disrupting compounds (EDC). Their impact on male fertility is still unknown., Methods: To explore the hypothesis that POP is associated with altered sperm chromatin integrity, a cross-sectional study involving 707 adult males (193 Inuits from Greenland, 178 Swedish fishermen, 141 men from Warsaw, Poland, and 195 men from Kharkiv, Ukraine) was carried out. Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), as a proxy of the total PCB burden, and of p,p'-DDE were determined. Sperm chromatin structure assay (SCSA) was used to assess sperm DNA/chromatin integrity., Results: We found a strong and monotonically increasing DNA fragmentation index with increasing serum levels of CB-153 among European but not Inuit men, reaching a 60% higher average level in the highest exposure group. No significant associations were found between SCSA-derived parameters and p, p'-DDE serum concentrations., Conclusion: These results suggest that human dietary PCB exposure might have a negative impact on the sperm chromatin integrity of adult males but additional issues, including differences in the genetic background and lifestyle habits, still need to be elucidated.

The concerted action EXASRUB was initiated to create a database management system for information on occupational hygiene measurements that could be used to develop exposure models in the European rubber manufacturing industry. Quality of coding was assessed by calculating percentages of agreement and Cohen's kappa statistics (kappa) for an intra- and inter-centre recoding of randomly selected subsets of the measurements. In a 6-month period, 59 609 measurements from 523 surveys in 333 factories from as early as 1956 to 2003 were coded. The database consists primarily of measurements of N-nitrosamines (36%), rubber dust (23%), solvents (14%) and rubber fumes (10%). Coding of epidemiologically relevant information was done consistently with inter-centre kappa between 0.86 and 1.00. For occupational hygiene information, values of kappa were estimated to be between 0.67 and 1.00. The proposed method resulted in a large quantity of exposure measurements with auxiliary information of varying completeness and quality. Analyses showed that coding of epidemiologically relevant information in such a multi-centre, multi-country study was coded consistently. Larger errors however, occurred in coding of occupational hygiene information. This was primarily caused by lack of information in the primary records of measurements, emphasizing the importance of having a universal system in place to collect and store measurement information by occupational hygienists for future use.

Background: A major exposure route for persistent organochlorine pollutants (POPs) in Sweden is through consumption of fatty fish from the Baltic Sea. Endocrine disruptors, such as POPs, may have a negative impact on sperm quality. The present study aimed to investigate whether exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) affects epididymal and accessory sex gland function., Methods: 157 fishermen from the coastal stretches of Sweden, aged 27-67 years, provided semen samples which were analyzed for prostate-specific antigen (PSA), neutral alpha-glucosidase (NAG), fructose and zinc levels. Serum levels of CB-153 and p'p-DDE were determined., Results: The median CB-153 serum level was 189 ng/g lipid (range 40-1460) and a median p,p'-DDE serum level 231 ng/g lipid (range 40-2252). There was a significant linear association between CB-153 and total amount of PSA (slope [beta] = -2.5, 95% confidence interval [CI] -4.0, -0.9; P = 0.02). With age, abstinence time and smoking included in the model the association became non-significant (beta = -1.4, 95% CI-3.0, 0.1; P = 0.07). There were no significant associations between CB-153 and zinc, fructose and NAG. As for the exposure variable p,p'-DDE and the outcome variables, no significant associations were found., Conclusions: The study gives only very limited support of an association between CB-153 in serum and total PSA, and a random finding cannot be excluded.

Background: During the last decades, there has been concern that exposure to endocrine disruptors, such as persistent organochlorine pollutants (POPs), may contribute to sex ratio changes in offspring of exposed populations., Methods: To investigate whether exposure to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE) affect Y:X chromosome proportion, semen of 149 Swedish fishermen, aged 27-67 years, was investigated. The men provided semen and blood for analysis of hormone, CB-153 and p,p'-DDE levels. The proportion of Y- and X-chromosome bearing sperm in semen samples was determined by two-colour fluorescence in situ hybridization (FISH) analysis., Results: Log transformed CB-153 as well as log transformed p,p'-DDE variables were both significantly positively associated with Y chromosome fractions (P-values = 0.05 and <0.001, respectively). Neither age, smoking nor hormone levels showed any association with Y-chromosome fractions., Conclusions: This is the first study to indicate that exposure to POPs may increase the proportion of ejaculated Y-bearing spermatozoa. These data add to the growing body of evidence that exposure to POPs may alter the offspring sex ratio.

Background: During the last decades, there has been concern that exposure to endocrine disruptors, such as persistent organochlorine pollutants (POPs), may contribute to an impairment of male reproductive function. To investigate whether exposure to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) affects semen quantity and quality and reproductive hormones, 195 Swedish fishermen, aged 24-65 years, were investigated., Methods: The men provided semen samples which were analysed in a mobile laboratory unit. Blood samples and information relating to lifestyle, medical and reproductive history were obtained., Results: The subjects had a median CB-153 serum level of 193 ng/g lipid (range 39-1460) and a median p,p'-DDE serum level of 240 ng/g lipid (range 334-2251). When CB-153 was categorized into quintiles, the subjects in the quintile with the highest concentration (> 328 ng/g lipid), tended to have decreased sperm motility compared with the subjects in the lowest quintile (< 113 ng/g lipid). The age-adjusted mean difference was 9.9% (95% confidence interval -1.0 to 21% P = 0.08). We found no significant associations between p,p'-DDE and semen characteristics or reproductive hormones., Conclusion: The association between CB-153 and sperm motility, although not formally significant, is of interest considering the possible endocrine-disrupting effects of polychlorinated biphenyls (PCBs).

Seasonal, daylight-dependent variation in human spermatozoa counts, with lowest values during summer, has been suggested. To test this hypothesis, we performed a longitudinal study of semen quality and reproductive hormone levels in Norwegian men living north and south of the Arctic Circle. An ejaculate and a serum specimen were obtained both in summer and in winter from 92 volunteers in Tromsoe (69 degrees north latitude) and 112 in Oslo (60 degrees north latitude). Semen analyses were performed, and serum was assayed for FSH and inhibin B. The median spermatozoa concentration in Tromsoe after adjustment for abstinence period length was 49 x 10(6)/ml in summer and 54 x 10(6)/ml in winter. Corresponding values for Oslo were 59 x 10(6)/ml and 54 x 10(6)/ml. The seasonal differences in spermatozoa concentration were not statistically significant, nor were significant differences observed in median total spermatozoa count, semen volume, percentage progressive motile spermatozoa, or FSH. In Tromsoe, but not Oslo, inhibin B concentration was slightly, but significantly (P = 0.02) higher in winter than summer (229 ng/liter vs. 223 ng/liter). The length of the daylight period may have a slight impact on hormonal markers of spermatogenesis but does not cause substantial changes in spermatozoa numbers and motility.

Background: Reduced life expectancy has been shown in patients with hypopituitarism, mainly caused by cardiovascular diseases. A major cause of hypopituitarism is pituitary adenomas, and radiotherapy may be employed as a treatment modality to reduce the post-operative regrowth rate of these tumours. Recently, we showed that in patients with craniopharyngiomas, tumour regrowth foreshadowed a fourfold risk increase for death. For patients with pituitary adenomas, the impact of regrowth on life expectancy is, however, not known., Objective: To assess the impact of a reoperation due to a regrowth of a pituitary macroadenoma on mortality, taking into account other candidate prognostic factors., Design and Patients: In 281 patients with operated and irradiated macroadenomas, excluding acromegaly and Cushing's disease, 35 patients had a regrowth (median follow-up 16.6 years). Possible risk factors for tumour regrowth were investigated by Cox regression models., Results: For tumour regrowth, age, calendar time at primary surgery, gender and extension of tumour growth had no statistically significant impact. For younger patients, the proportion of regrowths was higher, but after age-stratified Cox regression analysis only regrowth was shown to have a significant impact on mortality, with a more than doubled mortality risk for patients with tumour regrowth as compared with the non-regrowing tumour patients (hazard ratio=2.24, P<0.001). This finding was corroborated by cohort analyses using the general population as an external comparison group., Conclusion: Among patients with irradiated pituitary macroadenomas, excluding acromegaly and Cushing's disease, a doubled mortality rate was observed for those reoperated for tumour regrowth as compared with patients with non-regrowing tumours.

The paper presents the exposure assessment method and quality control procedure used in an international, multi-centre case-control study within a joint Nordic and Italian cohort. This study was conducted to evaluate whether occupational exposure to carcinogens influenced the predictivity of high frequency of chromosomal aberrations (CA) in peripheral lymphocytes for increased cancer risk. Occupational hygienists assessed exposures in each participating country: Denmark, Finland, Italy, Norway and Sweden. The exposure status to a carcinogen or a clastogen was coded in the cohort according to the original CA studies at the time of CA testing, but not for the whole work life. An independent occupational hygienist coordinated harmonization of the assessment criteria and the quality control procedure. The reliability of the exposure assessments was calculated as deviation from the majority of the assessors, as Cohen's kappa and as overall proportion of the agreements. The reassessment of the exposures changed the exposure statuses significantly, when compared with the original cohort. Harmonization of the exposure criteria increased the conformity of the assessments. The prevalence of exposure was higher among the original assessors (the assessor from the same country as the subject) than the average prevalence assessed by the other four in the quality control round. The original assessors classified more job situations as exposed than the others. Several reasons for this are plausible: real country-specific differences, differences in information available to the home assessor and the others and misunderstandings or difficulties in translation of information. To ensure the consistency of exposure assessments in international retrospective case-control studies it is important to have a well-planned study protocol. Due to country-specific environments a hygienist from each participating country is necessary. A quality control study is recommended, to be performed as described, combined with round-table meetings to minimize information bias between the assessors.

Vascular mortality, especially cerebrovascular disease (CVD), are the most pronounced cause of mortality in women with hypopituitarism. In a cohort of 342 patients operated and irradiated for pituitary tumors, 31 died from CVD (CVD patients) between 1952 and 1996. The study assessed whether the radiation regimens and duration of symptoms of hypopituitarism before operation differed between the 31 CVD patients and the 62 matched patients from the same cohort who had not died from CVD (control patients). Furthermore, the infarction/hemorrhage ratio, type of clinical stroke syndrome, and time to death after stroke were investigated in the CVD patients and in matched controls from the general population who had died from CVD (population controls). No significant differences in maximum or centrally absorbed dose, maximum or central biological equivalent dose, field size, or number of fraction were recorded between CVD and control patients. A significant difference in the duration of symptoms of hypopituitarism before operation was recorded, but only in women (P = 0.01). There were no significant differences in the infarction/hemorrhage ratio (P > 0.3) of lacunar or posterior circulation syndrome compared with middle cerebral artery syndrome with cortical features (P = 0.22) or the proportion of patients who died within the first month after stroke onset (60% vs. 59%, respectively) between CVD patients and population controls. In conclusion, no significant effect on CVD deaths could be detected for any radiation parameter. A long history of unsubstituted pituitary insufficiency may be a contributing factor to the very high CVD mortality among women. There were no indications of significant differences in type of stroke, clinical stroke syndromes, or stroke fatality between the CVD patients and the population controls.

Background: A common aetiology behind time-related deterioration of male reproductive function, including decline of sperm concentration and rising incidence of testicular cancer and cryptorchidism, has been suggested. Accordingly, a high incidence of testicular cancer and low sperm counts have been observed in Denmark, while in Finland opposite figures were found. This may be due to genetic factors. The incidence of testicular cancer is 50% lower in Sweden than in Denmark. Data on sperm counts in a population of Danish military conscripts have been published and we wished therefore to compare them with semen parameters in a corresponding cohort from Southern Sweden, geographically and genetically very closely related to Denmark., Methods: A total of 305 military conscripts was recruited and investigated in an identical way as those in the Danish study including a questionnaire, physical examination and semen analysis., Results: Men born and raised in Sweden had a 23% higher mean sperm concentration, a 31% higher mean total sperm count and a 14% higher seminal volume compared with their Danish counterparts., Conclusions: The differences in reproductive parameters between the two genetically very similar populations could not be explained by possible confounders and may be due to unknown environmental or lifestyle-related factors.

Objective: To explore the risk factors that have been suggested to be associated with the development of SLE., Methods: A case-control study was performed and a questionnaire was developed to obtain the data. Consecutive female incident cases diagnosed between 1981 and 1999 in a defined geographical area in southern Sweden were included. Controls, matched for calendar year of birth, were selected randomly from the same area. In total, 85 cases and 205 controls agreed to participate. The questionnaire included questions about formal education, body weight and height, medical history, family history of autoimmune diseases, exposure to ultraviolet radiation, animals, hair-colouring dyes, alfalfa (lucerne) sprouts, smoking and alcohol habits, history of physical traumata, blood transfusion, silicone breast implants, exogenous oestrogens, other medication, and significant negative life events., Results: Using a multivariate model, a history of hypertension [odds ratio (OR)=3.7, 95% confidence interval (CI) 1.4-9.8], drug allergy (OR=3.6, 95% CI 1.4-9.5), a type I/II sun-reactive skin type (OR=2.3, 95% CI 1.1-4.8) and a family history of SLE (OR=6.8, 95% CI 1.4-32) were all significantly associated with an increased risk of developing SLE, whereas consumption of alcohol was inversely associated with the risk of SLE (use of alcohol very seldom, OR=1.0; 1-150 g/month, OR=0.4, 95% CI 0.2-1.0; >150 g/month, OR=0.2, 95% CI 0.1-0.5). A suggested association with increased SLE risk was seen for smoking (OR=1.8, 95% CI 0.9-3.6) and blood transfusions (OR=2.3, 95% CI 0.9-5.8). Neither exposure to exogenous oestrogen nor exposure to hair-colouring dyes was associated with SLE., Conclusions: Risk factors of both exogenous and endogenous origin were identified in this population-based series of SLE patients.

Recently, an association between increased blood levels of insulin-like growth factor I (IGF-I) and increased risks of prostate, breast, lung, and colorectal cancers has been suggested. As today adults with GH deficiency are subjected to GH substitution, there is a pressing need for baseline tumor incidence data. The aim of the study was to assess the risk for a second tumor in a cohort of 328 patients with hypopituitarism treated for a pituitary tumor from 1958--1992. The patients were receiving conventional hormone treatment, but without GH substitution. The overall tumor incidence [standardized incidence ratio (SIR)] was lower than expected (0.85), but the 95% confidence interval (CI) did not exclude unity (0.59--1.21). Only two prostate cancers occurred (SIR, 0.34; 95% CI, 0.04--1.24). Two brain tumors (SIR, 1.96; 95% CI, 0.24--7.08) and two endocrine tumors (part of multiple endocrine neoplasm syndromes; SIR, 4.00; 95% CI, 0.48--14.5) had occurred. When excluding brain and endocrine tumors, the overall SIR decreased to 0.77, but did still not differ significantly from unity (0.52--1.13). Thus, a tendency for a decreased overall tumor risk, although not statistically significant, was noted, especially when excluding brain and endocrine tumors. This tendency was more emphasized for prostate cancer, but low numbers hamper a firm conclusion. These results may serve as a baseline for tumor risk among adult patients with pituitary insufficiency supplemented with GH.

We recently reported that female patients with hypopituitarism receiving controlled thyroid and steroid hormone substitution, but without GH replacement, had a more than 2-fold increase in cardiovascular mortality compared to the general population. In the present study we investigated the incidence of cardiovascular disease as well as the prevalence of cardiovascular risk factors in 33 females with hypopituitarism for 6-46 yr (median, 18) compared to those in 33 control subjects recruited from the general population in the same geographical area and matched for sex, age, smoking habits, educational level, and residence location. The patients were with a very high probability GH deficient, as 29 had subnormal serum insulin-like growth factor I levels, and the other 4 were GH deficient, as assessed by an insulin tolerance test. The incidence of cardiovascular disease was significantly higher among the hypopituitary patients (incidence ratio, 3.7; 95% confidence interval, 1.2-11.3), and the consumption of cardioactive drugs was also significantly higher (P = 0.002). Hypopituitary patients had a lower degree of physical exercise during their spare time (P = 0.02), a higher waist/hip ratio (P = 0.01), lower high density lipoprotein cholesterol (P = 0.002), and higher low density/high density lipoprotein ratio (P = 0.009). Furthermore, the patients had a significantly increased left atrium size (P = 0.05), but no difference was observed for other cardiac measures. In the patients, serum insulin-like growth factor I levels significantly correlated with left ventricular mass index (r = 0.48; P = 0.006), suggesting that GH has a strong impact on cardiac size. More episodes of bradycardia (P = 0.05), but no increased occurrence of extrasystolies, were encountered in the patients during 24-h continuous electrocardiogram monitoring. Carotid artery intima-media thickness and plaque numbers did not differ between patients and controls. In conclusion, hypopituitary females exhibit an increased incidence of cardiovascular disease, higher cardioactive drug consumption, and an increased prevalence of cardiovascular risk factors. The increased cardiovascular morbidity could not be ascribed to inadequate estrogen or thyroid hormone treatment, and unsubstituted GH deficiency is probably an important contributing factor.

Specific causes of death, survival, and recurrence rates were assessed in a cohort of 60 patients who had undergone surgery for craniopharyngioma between 1951 and 1988. Compared to the general population, the standardized mortality ratio (SMR) was increased [5.55; 95% confidence interval (CI), 3.68-8.22], and it was higher among females (SMR, 11.4) than males (SMR, 4.79). The risk of cardio- and cerebrovascular mortality (SMR, 3.21; 95% CI, 1.29-6.61) was also enhanced. The cumulative survival rates 10 and 15 yr after the initial operation were 68% (95% CI 54-78) and 59% (95% CI 30-63), respectively. A multivariate survival analysis adjusting for age showed a protective effect of radiotherapy (hazard ratio, 0.3; 95% CI, 0.1-0.8) and an increased risk of death after recurrence (hazard ratio, 4.4; 95% CI, 1.4-14), but no obvious effect of radicality at surgery. However, when patients who had died within 6 months after surgery were excluded, no significant protective effect of radiotherapy remained. The cumulative frequency of recurrence after 10 yr was 33% (95% CI, 22-48%), and that after 15 yr was 40% (95% CI, 28-56%). The incidence of recurrence did not differ significantly with respect to age, radicality at surgery, or postoperative radiotherapy. The determinants for long term outcome in patients with craniopharyngioma are interrelated in a complex way, which calls for strict selection criteria in follow-up studies and the use of multivariate statistical models.

The authors examined the hypothesized association between the body burden of polychlorinated biphenyls (PCB) in women and the risk of low birth weight for their infants. In Sweden, a main exposure route for PCBs and other persistent organochlorine compounds is through the consumption of fatty fish from the Baltic Sea (on the Swedish east coast). A previous comparison between a cohort of consumers of large quantities of fish from the Swedish east coast and a reference population, together with a following analysis based on questionnaire data from a case-control study within the east coast cohort, supported the hypothesized association. In 1995, blood samples were collected from the wives and ex-wives of fishermen from the Swedish east coast (n = 192) who had given birth during the period 1973-1991. Cases (n = 57), i.e., infants with low birth weight (1,500-2,750 g), were matched with controls (n = 135; birth weight, 3,250-4,500 g) on gender, parity, and calendar year of birth. The concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma was analyzed; it has been suggested that CB-153 is a relevant biomarker of exposure to PCBs. The concentration of CB-153 in the plasma of mothers during the year of childbirth was "estimated" using some alternative plausible kinetic models. For two alternative estimated exposure datasets, which were focused on separately, an increase in the risk of a low birth weight was observed at a CB-153 concentration of 300 and 400 ng/g lipid weight, respectively (adjusted odds ratios of 2.1 (95% confidence interval (CI) 1.0-4.7) and 2.3 (95% CI 0.9-5.9)). The present results strengthen the findings reported previously for this study population.

In an attempt to study further the age-specific influence on the hypothalamo-pituitary-gonadal axis as well as the hypothalamo-pituitary-thyroid axis, we have now investigated young and middle-aged men, considering possible confounding factors. Both serum total testosterone, free testosterone and the total ratio of testosterone to sex-hormone binding globulin were significantly lower among middle-aged men as compared with young men (p = 0.02, p = 0.002 and p = 0.0003, respectively). In accordance with these findings there was also a decrease in the luteinizing hormone response to gonadotrophin-releasing hormone in the middle-aged men (p = 0.02). Free testosterone was correlated significantly with the luteinizing hormone response (r = 0.32, p = 0.02). Serum free triiodothyronine was significantly higher among young men as compared with middle-aged men (p = 0.002) and the thyrotrophin-releasing hormone-stimulated thyrotrophin response was also higher in the young group compared with the middle-aged group. The present results may indicate that the age effect on serum levels of testosterone and free triiodothyronine is mediated at the pituitary level.

There are 209 congeners of polychlorinated biphenyls (PCBs), the metabolism and toxicity of which vary by congeners. Use of PCBs is now restricted, but environmental contamination and human exposure persist. Analysis for "total PCBs" in biological samples gives limited information; congener-specific analysis is far more informative, but more complicated. Concentrations of congeners in serum/plasma, adipose tissue, or milk are useful biomarkers of exposure. Lipids may contain similar concentrations and congener patterns, but these vary between exposures and are different from those of the corresponding exposure mixtures; hence, analysis of lipids cannot be used to identify the original exposure. Some non- and mono-ortho congeners may attain a coplanar conformation, which renders them capable of a dioxin-like action. Toxic equivalency factors (TEFs) have been used to sum that risk as toxic equivalents (TEQs), which are considerably different from congener concentrations. No reliable data have been developed on the relationship between concentrations of "total PCBs" or congeners in biological samples and effects of PCBs on human health, mainly because of the various analytical procedures involved and confounding exposures.

In a cross-sectional study adjusting for age, gender, and catchment area, the prevalence of thyroid antibodies was assessed in 51 consecutive subjects with biopsy-proven glomerulonephritis and in 112 control subjects admitted for extracorporeal shock-wave lithotripsy treatment for renal stones. Women with glomerulonephritis had both a significantly greater prevalence of thyroid peroxidase antibodies (odds ratio 3.85, 95% confidence interval 1.04-14.3) and an increased prevalence of elevated serum TSH values (P = 0.007). No such difference was found in men. The prevalence of thyroglobulin antibodies did not differ between the groups. It is suggested that the possibility of an autoimmune thyroid disease should be taken into consideration in patients with glomerulonephritis, particularly in women.