Background: It has been hypothesized that thyroid function may influence cancer risk, but few studies with adequate statistical power have investigated this question, and the results have not been consistent. Methods: In a prospective study of 29,691 people (19,710 women and 9,981 men) without previously known thyroid disease, thyrotropin was measured at baseline, and cancer incidence was recorded during 9 years of follow-up. Using Cox regression analysis, we studied the associations (hazard ratios) of thyrotropin categories with total cancer risk, and specifically, with risk of lung, colon, prostate, and breast cancer adjusted for age, sex, and smoking status. Results: Low thyrotropin levels (<0.50 mU/L) were associated with increased cancer risk [adjusted hazard

Objective To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy. Design Nested case-control study during pregnancy and population based follow-up study after pregnancy. Setting Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous women in the United States during 1992-5, and a Norwegian population based study (Nord-Trondelag Health Study or HUNT-2) during 1995-7 with linkage to the medical birth registry of Norway. Participants All 141 women (cases) in the Calcium for Preeclampsia Prevention trial with serum measurements before 21 weeks' gestation (baseline) and after onset of pre-eclampsia (before delivery), 141 normotensive controls with serum measurements at similar gestational ages, and 7121 women in the Nord-Trondelag Health Study whose first birth had occurred in 1967 or later and in whom serum levels of thyroid stimulating hormone had been subsequently measured. Main outcome measures Thyroid function tests and human chorionic gonadotrophin and soluble fms-like tyrosine kinase 1 concentrations in the Calcium for Preeclampsia Prevention cohort and odds ratios for levels of thyroid stimulating hormone above the reference range, according to pre-eclampsia status in singleton pregnancies before the Nord-Trondelag Health Study. Results In predelivery specimens of the Calcium for Preeclampsia Prevention cohort after the onset of preeclampsia, thyroid stimulating hormone levels increased 2.42 times above baseline compared with a 1.48 times increase in controls. The ratio of the predelivery to baseline ratio of cases to that of the controls was 1.64 (95% confidence interval 1.29 to 2.08). Free triiodothyronine decreased more in the women with preeclampsia than in the controls (case ratio to control ratio 0.96, 95% confidence interval 0.92 to 0.99). The predelivery specimens but not baseline samples from women with pre-eclampsia were significantly more likely than those from controls to have concentrations of thyroid stimulating hormone above the reference range (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4). Both in women who developed pre-eclampsia and in normotensive controls the increase in thyroid stimulating hormone concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1 (P for trend 0.002 and <0.001, respectively). In the NordTrondelag Health Study, women with a history of preeclampsia in their first pregnancy were more likely than other women (adjusted odds ratio 1.7, 95% confidence interval 1.1 to 2.5) to have concentrations of thyroid stimulating hormone above the reference range (>3.5 mIU/l). In particular, they were more likely to have high concentrations of thyroid stimulating hormone without thyroid peroxidase antibodies (adjusted odds ratio 2.6, 95% confidence interval 1.3 to 5.0), suggesting hypothyroid function in the absence of an autoimmune process. This association was especially strong (5.8, 1.3 to 25.5) i...

ObjectiveBiochemical changes associated with obesity may accelerate osteoarthritis beyond the effect of mechanical factors. This study investigated whether metabolic syndrome and its components (visceral obesity, hypertension, dyslipidemia and insulin resistance) were risk factors for subsequent total hip replacement (THR) or total knee replacement (TKR) due to primary osteoarthritis.DesignIn this prospective cohort study, data from the second survey of the Nord-Trøndelag Health Study 2 (HUNT2) were linked to the Norwegian Arthroplasty Register for identification of the outcome of THR or TKR. The analyses were stratified by age (<50, 50–69.9 and ≥70 years) and adjusted for gender, body mass index, smoking, physical activity and education.ResultsOf the 62,661 participants, 12,593 (20.1%) were identified as having metabolic syndrome, and we recorded 1,840 (2.9%) THRs and 1,111 (1.8%) TKRs during a mean follow-up time of 15.4 years. Cox regression analyses did not show any association between full metabolic syndrome and THR or TKR, except in persons <50 years with metabolic syndrome who had a decreased risk of THR (hazard ratio [HR] 0.58, 95% CI 0.40–0.83). However, when including only participants whose exposure status did not change during follow-up, this protective association was no longer significant. Increased waist circumference was associated with increased risk of TKR in participants <50 years (HR 1.62, 95% CI 1.10–2.39) and 50–69.9 years (HR 1.43, 95% CI 1.14–1.80). Hypertension significantly increased the risk of TKR in participants <50 years (HR 1.38, 95% CI 1.05–1.81), and this risk was greater for men.ConclusionThis study found an increased risk of TKR in men <50 years with hypertension and persons <70 years with increased waist circumference. Apart from this, neither metabolic syndrome nor its components were associated with increased risk of THR or TKR due to primary osteoarthritis.

We found that increasing age at menarche reduced the risk of TKR. Past users and users of systemic HRT were at higher risk of TKR compared to never users. Parity did not increase the risk of THR or TKR.

Objective: Smoking has been associated with a reduced risk of hip and knee osteoarthritis and subsequent joint replacement. The aim of the present study was to assess whether the observed association is likely to be causal.Method: 55 745 participants of a population-based cohort were genotyped for the rs1051730 C>T single-nucleotide polymorphism, a proxy for smoking quantity among smokers.A Mendelian randomization analysis was performed using rs1051730 as an instrument to evaluate the causal role of smoking on the risk of hip or knee replacement (combined as total joint replacement (TJR)). Association between rs1051730 T alleles and TJR was estimated by hazard ratios (HRs) and 95% confidence intervals (CIs). All analyses were adjusted for age and sex. Conclusion:This study suggests that smoking may be causally associated with the reduced risk of TJR. Our findings add support to the inverse association found in previous observational studies. More research is needed to further elucidate the underlying mechanisms of this causal association.

To investigate the total effect of smoking on total hip or knee replacement (THR/TKR) due to primary osteoarthritis (OA) and to quantify the indirect effect of smoking through body mass index (BMI). Participants from the Nord-Trøndelag Health Study (the HUNT Study) were linked to the Norwegian Arthroplasty Register to detect the first THR or TKR due to primary OA. A mediation analysis was used to decompose the total effect of smoking into a direct and indirect effect. BMI was considered a mediator in the analysis. All effects were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs). The indirect effect of smoking mediated through BMI was expressed as a percentage (proportion*100). In total 55 188 participants were followed up during 17.2 years (median). We identified 1322 THRs and 754 TKRs. For men, the total effect of current vs. never smoking revealed a decreased risk of THR (HR 0.59, 95% CI 0.46–0.76) and TKR (HR 0.47, 95% CI 0.32–0.66). For women, current smoking increased the risk of THR (HR 1.34, 95% CI 1.11–1.60). For men, 6% and 7% of the risk reduction for THR and TKR, respectively, was mediated by BMI. We found a negative association between smoking and THR or TKR for men. On the contrary, smoking was associated with increased risk of THR for women. Most of the effect of smoking on joint replacement risk remained unexplained by BMI.

This study investigated whether excess amounts of soluble fms-like tyrosine kinase 1 in patients with pre-eclampsia might be associated with reduced thyroid function during and after pregnancy. The first part of the study was a nested case-control study within the Calcium for Pre-eclampsia Prevention trial conducted between 1992 and 1995 in the United States. Thyroid function during pregnancy was compared in nulliparous singletons with pre-eclampsia (case group, n ϭ 141) and without pre-eclampsia (normotensive control group, n ϭ 141). The second part was a follow-up population-based study, the Nord-Trondelag Health Study (HUNT-2), that investigated whether pre-eclampsia in a previous pregnancy increased the risk of reduced thyroid function later in life. The HUNT-2 study participants were 7121 women who had delivered their first child during or after 1967.In the Calcium for Pre-eclampsia Prevention trial, after the onset of pre-eclampsia and before delivery, the increase in thyroid-stimulating hormone (TSH) concentrations from baseline levels was higher in the case than in the control group (2.48 vs. 1.48 times above baseline). Comparison of the TSH predelivery to baseline ratios in the cases and controls showed that the case ratio was 1.64 times higher (95% confidence interval [CI], 1.29-2.08). Significantly greater reductions occurred in levels of free triiodothyronine in women with pre-eclampsia compared to controls; the case ratio to control ratio was 0.96, with a 95% CI of 0.92-0.99. In predelivery but not baseline specimens, women with pre-eclampsia were significantly more likely than controls to have concentrations of TSH above the reference range (adjusted odds ratio [OR], 2.2; 95% CI, 1.1-4.4). The increase in TSH concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1, in both women who developed pre-eclampsia and in normotensive controls (P for trend Ͻ0.002 and Ͻ0.001, respectively). In the HUNT-2 study, the probability of having serum TSH concentrations greater than the clinical reference range (Ͼ3.5 mIU/L) was higher among women with a history of pre-eclampsia in their first pregnancy in comparison to those who did not develop pre-eclampsia in their first pregnancy (adjusted OR, 1.7; 95% CI, 1.1-2.5). The association of pre-eclampsia in the first pregnancy with high concentrations of TSH (Ͼ4.0 mIU/L) was more likely in the absence of thyroid peroxidase antibodies (adjusted OR, 2.6; 95% CI, 1.3-5.0).The association with hypothyroid function was particularly strong in women who had experienced pre-eclampsia in 2 pregnancies (adjusted OR, 5.8; 95% CI,.These findings suggest that increased serum concentration of soluble fms-like tyrosine kinase 1, especially after onset of pre-eclampsia, is associated with a greater subsequent risk of subclinical hypothyroidism during pregnancy and that a history of pre-eclampsia increases the risk of sub-clinical hypothyroidism in later years. EDITORIAL COMMENT(Levine et ...

BackgroundThe relationship between leisure time physical activity (LPA) and hip and knee OA and subsequent joint replacement has not yet been clearly defined. Some studies have found the risk of knee replacement (TKR) to increase with high levels of LPA, while others have found no overall relationship to either TKR or hip replacement (THR). The aim was to investigate the association between LPA and the risk of severe end-stage OA, defined as THR or TKR due to primary OA, in a large population-based cohort.MethodsParticipants in the Nord-Trøndelag Health Study (HUNT) were followed prospectively to identify THR and TKR using the Norwegian Arthroplasty Register. Self-reported LPA was classified as inactive, low, moderate or high. The Cox proportional hazards model was used to calculate hazard ratios (HRs) according to levels of LPA with adjustments for confounding variables. Analyses were performed by age (<45, 45–59 and ≥60 years) and sex.ResultsA total of 66 964 participants (mean age 46.8 years (SD 16.3) were included in the analyses. We identified 1636 THRs and 1016 TKRs due to primary OA during 17.0 years (median) of follow-up. High LPA was significantly associated with THR for women <45 years (HR 1.78, 95 % CI 1.08–2.94) and men between 45–59 years (HR 1.53, 95 % CI 1.10–2.13) at baseline. A significant trend was found only among women < 45 years at baseline (p = 0.02). We found that LPA was significantly associated with TKR for women only (HR 1.45, 95 % CI 1.03–2.04). No measures of LPA were associated with TKR for men.ConclusionIn this population-based study, high level of LPA was associated with increased risk of THR where a significant trend of LPA was seen among women <45 years at baseline. For TKR, high LPA was associated with increased risk only in women. In contrast to previous studies, this study shows a possible association between high LPA and the risk of THR.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-0937-7) contains supplementary material, which is available to authorized users.