Prospective risk of Type 2 diabetes in 99 892 Nordic women with polycystic ovary syndrome and 446 055 controls: national cohort study from Denmark, Finland, and Sweden.

STUDY QUESTION: What is the prospective risk of Type 2 diabetes (T2D) in Nordic women with polycystic ovary syndrome (PCOS) compared to controls? SUMMARY ANSWER: A diagnosis of PCOS and BMI ≥30 kg/m2 is a high-risk phenotype for a prospective risk of T2D diagnosis across Nordic countries. WHAT IS KNOWN ALREADY: The risk of T2D in women with PCOS is increased. The risk of T2D is related to BMI and the magnitude of risk in normal weight women with PCOS has been discussed. However, prospective data regarding risk of T2D in population-based cohorts of women with PCOS are limited. STUDY DESIGN, SIZE, DURATION: This national register-based study included women with PCOS and age-matched controls. The main study outcome was T2D diagnosis occurring after PCOS diagnosis. T2D was defined according to ICD-10 diagnosis codes and/or filled medicine prescriptions of anti-diabetic medication excluding metformin. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort included women originating from Denmark (PCOS Denmark, N = 27 016; controls, N = 133 994), Finland (PCOS Finland, N = 20 467; controls, N = 58 051), and Sweden (PCOS Sweden, N = 52 409; controls, N = 254 010). The median age at cohort entry was 28 years in PCOS Denmark, Finland, and Sweden with a median follow-up time (interquartile range) in women with PCOS of 8.5 (4.0-14.8), 9.8 (5.1-15.1), and 6.0 (2.0-10.0) years, respectively. Cox regression analyses were adjusted for BMI and length of education. MAIN RESULTS AND THE ROLE OF CHANCE: The crude hazard ratio (HR, 95% CI) for T2D diagnosis in women with PCOS was 4.28 (3.98-4.60) in Denmark, 3.40 (3.11-3.74) in Finland, and 5.68 (5.20-6.21) in Sweden. In adjusted regression analyses, BMI ≥30 vs <25 kg/m2 was associated with a 7.6- to 11.3-fold risk of T2D. In a combined meta-analysis (PCOS, N = 99 892; controls, N = 446 055), the crude HR for T2D in PCOS was 4.64 (3.40-5.87) and, after adjustment for BMI and education level, the HR was 2.92 (2.32-3.51). LIMITATIONS, REASONS FOR CAUTION: Inclusion of more severe cases of PCOS in the present study design could have lead to an overestimation of risk estimates in our exposed population. However, some women in the control group would have undiagnosed PCOS, which would lead to an underestimation of T2D risk in women with PCOS. BMI data were not available for all participants. The present study should be repeated in study cohorts with higher background risks of T2D, particularly in populations of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: The prospective risk for diagnosis of T2D is increased in women with PCOS, and the risk is aggravated in women with BMI ≥30 kg/m2. STUDY FUNDING/COMPETING INTEREST(S): Funding in Denmark was from the Region of Southern Denmark, Overlægerådet, Odense University Hospital. Funding in Finland was from Novo Nordisk Foundation, Finnish Research Council and Sigrid Juselius Foundation, the National Regional Fund, Sakari Alhopuro Foundation and Finnish Diabetes Research Foundation. E.E. has received a research grant from Ferring Pharmaceuticals (payment to institution) and serves as medical advisor for Tilly AB, not related to this manuscript. The remaining authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Chronotype and metabolic syndrome in midlife: findings from the Northern Finland Birth Cohort 1966.

Evening chronotype is known to be associated with various chronic diseases and cardiovascular risk factors. Metabolic syndrome is a group of conditions that together raise the risk of coronary heart disease, diabetes, stroke, and other serious health problems. Only a few studies have been published on the association between chronotype and metabolic syndrome in unselected population data, with conflicting results. The aim of this study was to evaluate the association between chronotype and metabolic syndrome at population level by using unselected Northern Finland Birth cohort 1966 (NFBC1966) database. The study population consists of participants with NFBC66 (n = 5,113, 57% female) at the age of 46 yr old. Chronotype was determined with shortened Morningness-Eveningness Questionnaires and expressed as morning (44%), intermediate (44%), and evening types (12%). Metabolic syndrome was determined according to the definition of International Diabetes Federation. One-way ANOVA, Kruskal-Walli's test, and χ2 tests were used to compare the chronotype groups, followed by logistic regression analysis (adjusted with alcohol consumption, smoking, marital status, level of education, and leisure-time physical activity). In women, the prevalence of metabolic syndrome was statistically significantly higher in the evening type group: 23, 24, and 34% for morning, intermediate, and evening groups, respectively (P < 0.001). In logistic regression analysis, evening chronotype was associated with higher risk of having metabolic syndrome (OR 1.5; CI 95% 1.2 to 2.0). In this population-based birth cohort study, the evening chronotype was independently associated with higher prevalence of metabolic syndrome in women.NEW & NOTEWORTHY Only a few studies have been conducted on the association between chronotype and metabolic syndrome in unselected population data, with conflicting results. In this population-based cohort study of 5,113 participants, the evening chronotype associated with metabolic syndrome in women when there was no such association in men. The result supports a previous South Korean population study of 1,620 participants, in which the association was also found in women, but not in men.

Polycystic ovary syndrome presents as a multimorbid condition by age 50: birth cohort linkage to national register data.

OBJECTIVE: This population-based follow-up study investigated register-based disease diagnoses and medication use up till age of 50 years among women with polycystic ovary syndrome (PCOS) that were identified from a population-based birth cohort. DESIGN: Population-based longitudinal cohort study. PATIENTS: Women reporting oligo/amenorrhea and hirsutism at age 31 and/or who were diagnosed with PCOS by a physician by age 46 (n = 244) and women without PCOS symptoms or diagnosis (n = 1556) in the Northern Finland Birth Cohort 1966. MAIN OUTCOME MEASURES: National register data on diagnosed diseases (International Statistical Classification of Diseases [ICD]-8-10) and medication use (Anatomical Therapeutic Chemical) until the age of 50. RESULTS: Women with PCOS had a 26% higher risk for any registered diagnosis (risk ratio [RR]: 1.26 [1.09-1.46]) and a 24% higher risk for medication use (RR: 1.24 [1.05-1.46]) compared with non-PCOS women, even after adjusting for several confounders. Several main ICD categories were more prevalent among women with PCOS versus non-PCOS controls, eg, endocrine, metabolic, nervous system, musculoskeletal, and genitourinary diseases in addition with different symptoms and injuries. Surprisingly, even though the overall morbidity was only increased in women with PCOS with a body mass index (BMI) ≥ 25 kg/m2, there were several ICD main categories that showed higher comorbidity risk especially in women with PCOS with a BMI < 25 kg/m2. Several medications were prescribed more often to women with PCOS versus non-PCOS controls, eg, medications related to the alimentary tract and metabolism, the cardiovascular system, genitourinary system drugs and sex hormones, dermatologic and hormonal preparations, and medications to treat the musculoskeletal, nervous, and respiratory systems. CONCLUSION: Women with PCOS are burdened with multimorbidity and higher medication use, independent of BMI and other confounders. Accordingly, preventive strategies are needed to alleviate the disease burden and improve the health outcomes of women with PCOS.

Radiological features and treatment of erupting maxillary canines in relation to the occurrence of dental developmental abnormalities.

OBJECTIVE: This study aimed to investigate the radiological features of the permanent canines and the treatment carried out to ensure their eruption relative to certain features involved in Dental Anomaly Patterns (DAP). MATERIAL AND METHODS: The cross-sectional part of this retrospective register--based study focused on 1,315 dental panoramic tomographs (DPTs) of children aged 8.5-10.5 years, while the longitudinal part involved information on the treatment provided for 1,269 canines after the DPTs and on their eruption into the oral cavity. RESULTS: The canines of the DAP children more often showed evidence of early treatment (p = 0.014), with girls having more frequently interceptive treatment (p = 0.004) and boys early headgear (p = 0.022). Delayed dental age was associated with early treatment (OR 3.29, 95% CI 1.08-9.99). Either no or clear overlapping of a canine with the lateral incisor occurred more often in the DAP children, whereas canine inclination did not differ between the groups. The root development stage of the canine was more often either beginning or well advanced in the DAP children. CONCLUSIONS: The children with dental developmental abnormalities more often showed evidence of early treatment for the canines. Monitoring of the erupting canines after the first mixed stage is important to enable timely early treatment.

Climacteric status at age 46 is associated with poorer work ability, lower 2-year participation in working life, and a higher 7-year disability retirement rate: a Northern Finland Birth Cohort 1966 study.

OBJECTIVE: To study the association between an advanced climacteric status at 46 years of age and current perceived work ability, the consequent 2-year accumulation of disability and unemployment days, and the 7-year incidence of disability pensions. METHODS: Study participants (n = 2,661) were recruited from the Northern Finland Birth Cohort 1966 study's 46-year follow-up in 2012. The participants' perceived work ability was investigated using the Work Ability Score (0-7 = poor vs 8-10 = good), along with potential covariates. Data concerning their consequent disability days, unemployment days, and disability pensions were collected from national registers. The association between their climacteric status at age 46 years, work ability, and working life participation was assessed using regression models. RESULTS: The climacteric women were more often smokers and more often had a lower level of education. The odds ratio for poor perceived work ability was 1.41 (95% CI, 1.06-1.87), and the incidence rate ratios for disability and unemployment days during the 2-year follow-up were 1.09 (95% CI, 1.07-1.11) and 1.16 (95% CI, 1.14-1.18), respectively, for the climacteric women compared with the preclimacteric women in models adjusted for smoking and education. The 7-year hazard ratio for disability pensions was 1.72 (95% CI, 1.02-2.91) for the climacteric women. CONCLUSIONS: An earlier menopausal transition is associated with poorer perceived work ability, and it predicts lower recorded work participation and a higher disability pension rate in subsequent years.

Previous cancers in women diagnosed with premature ovarian insufficiency: A nationwide population-based case-control study.

INTRODUCTION: To investigate the occurrence of previous cancer diagnoses in women suffering from premature ovarian insufficiency (POI) and compare it with the general population, shedding light on the association between cancer, cancer treatments, and POI. MATERIAL AND METHODS: We conducted a nationwide case-control study based on registry data from various sources, including the Social Insurance Institution, Finnish Population Information System, and Finnish Cancer Registry spanning from 1953 to 2018. Our participants comprised all women in Finland who, between 1988 and 2017, received hormone replacement therapy reimbursement for ovarian insufficiency before the age of 40 years (n = 5221). Controls, matched in terms of age and municipality of residence, were selected from the Finnish Population Information System (n = 20 822). Our main exposure variable was a history of cancer diagnosis preceding the diagnosis of POI. We analyzed odds ratios (OR) to compare the prevalence of previous cancers in women with POI with that in controls, stratifying results based on cancer type, age at cancer diagnosis, and the time interval between cancer diagnosis and POI. We also assessed changes in OR for previous cancer diagnoses over the follow-up period. RESULTS: Out of the women diagnosed with POI, 21.9% had previously been diagnosed with cancer, resulting in an elevated OR of 36.5 (95% confidence interval [CI] 30.9 to 43.3) compared with 0.8% of the controls. The risk of developing POI was most pronounced during the first 2 years following a cancer diagnosis, with an OR of 103 (95% CI 74.1 to 144). Importantly, this risk remained elevated even when the time interval between cancer and POI exceeded 10 years, with an OR of 5.40 (95% CI 3.54 to 8.23). CONCLUSIONS: This study reveals that 21.9% of women with POI have a history of cancer, making the prevalence of cancer among these women 27.5 times higher than age-matched controls in the Finnish population. The risk of developing POI is most substantial in the first 2 years following a cancer diagnosis. These findings underscore the role of cancer treatments as an etiological factor for POI and emphasize the importance of recognizing the risk of POI in cancer survivors for early diagnosis and intervention.

Sleep disturbances in women with early-onset menopausal transition: a population-based study.

OBJECTIVE: The aim of this study was to investigate sleep disturbances in 46-yr-old women and their association with early-onset menopausal transition. METHODS: The women of this cross-sectional birth cohort study were divided into climacteric (n = 359) and preclimacteric (n = 2,302) groups by their menopausal status, defined by follicle-stimulating hormone levels and menstrual history. Sleep disturbances were evaluated with Athens Insomnia Scale 5. We performed univariable and multivariable logistic regression models in which sleep parameters were dependent variables and climacteric status, hot flashes, smoking, and education level were independent variables. The use of hormone therapy was also evaluated in women suffering from sleeping disturbances. RESULTS: On the basis of the scale questions, climacteric women experienced significantly delayed sleep induction (12.2% vs 8.7%, P = 0.047), more problems with awakenings during the night (23.4% vs 14.6%, P < 0.001), earlier final awakening (13.8% vs 9.9%, P = 0.039), and more unsatisfying sleep quality (11.9% vs 7.9%, P = 0.023). Climacteric women who were experiencing hot flashes reported unsatisfactory sleep quality more frequently compared with climacteric women who did not experience hot flashes (17.0% vs 9.2%, P = 0.047). In the univariable and multivariable logistic regression models, being climacteric was independently associated with different impaired sleeping parameters. Most climacteric women who had a scale score of 4 or greater were not using hormone therapy, according to their medicine purchases over the past year. CONCLUSIONS: Being climacteric was associated with sleep disturbances in women in their mid-40s. However, this association seemed to be particularly driven by hot flashes. Most climacteric women with clinically significant sleeping disturbances were not using hormone therapy.

1,25(OH)2D3 and its analogue calcipotriol inhibit the migration of human synovial and mesenchymal stromal cells in a wound healing model - A comparison with glucocorticoids.

Vitamin D analogue calcipotriol is currently used in the local treatment of psoriasis. However, it also has antiproliferative and anti-inflammatory effects in the cells of the joint - suggesting a possible benefit in local treatment of arthritis. In this study, calcipotriol was studied in different in vitro methods to find out its effect on synovial and mesenchymal stromal cells. Primary human cell lines of osteoarthritis or rheumatoid arthritis patients (five mesenchymal stromal cells, MSC, and four synovial stromal cells, SSC) were cultured to study migration and proliferation of the cells in a wound healing model. The media was supplemented with calcipotriol, 1,25(OH)2D3, dexamethasone, betamethasone, methylprednisolone or control solution in 1-100 nM concentrations. To see possible toxic effects of calcipotriol, concentrations up to 10 µM in SSCs and MSCs were studied in apoptosis and necrosis assays in four cell lines. Calcipotriol and 1,25(OH)2D3, as well as the three glucocorticoids, reduced the migration of both SSCs and MSCs. In SSCs, the effect of calcipotriol and 1,25(OH)2D3 was at least as effective as with glucocorticoids, while with MSCs, the glucocorticoids were stronger inhibitors of migration. The antimigratory of calcipotriol and 1,25(OH)2D3 was consistently maintained in 10 µM and 1 µM. Calcipotriol was not toxic to MSCs and SSCs up to concentrations of 10 µM. Calcipotriol, as well as 1,25(OH)2D3, exerts antimigratory and antiproliferative effects on human SSCs and MSCs of the joint. These effects are not caused by apoptosis or necrosis. Both calcipotriol and 1,25(OH)2D3 have similar effects as glucocorticoids without apparent toxicity, suggesting that calcipotriol might be an eligible candidate to the local treatment of arthritis with a broad therapeutic window.

Low and high serum IgG associates with respiratory infections in a young and working age population.

BACKGROUND: We investigated health consequences and genetic properties associated with serum IgG concentration in a young and working age general population. METHODS: Northern Finland Birth Cohort 1966 (NFBC1966, n = 12,231) health data have been collected from birth to 52 years of age. Relationships between life-long health events, medications, chronic conditions, lifestyle, and serum IgG concentration measured at age 46 years (n = 5430) were analysed. Regulatory mechanisms of serum IgG concentration were considered. FINDINGS: Smoking and genetic variation (FCGR2B and TNFRSF13B) were the most important determinants of serum IgG concentration. Laboratory findings suggestive of common variable immunodeficiency (CVID) were 10-fold higher compared to previous reports (73.7 per 100,000 vs 0.6-6.9 per 100,000). Low IgG was associated with antibiotic use (relative risk 1.285, 95% CI 1.001-1.648; p = 0.049) and sinus surgery (relative risk 2.257, 95% CI 1.163-4.379; p = 0.016). High serum IgG was associated with at least one pneumonia episode (relative risk 1.737, 95% CI 1.032-2.922; p = 0.038) and with total number of pneumonia episodes (relative risk 2.167, 95% CI 1.443-3.254; p < 0.001). INTERPRETATION: CVID-like laboratory findings are surprisingly common in our unselected study population. Any deviation of serum IgG from normal values can be harmful; both low and high serum IgG may indicate immunological insufficiency. Critical evaluation of clinical presentation must accompany immunological laboratory parameters. FUNDING: Oulu University Hospital VTR, CSL Behring, Foundation for Pediatric Research.

Association of climacterium with temporomandibular disorders at the age of 46 years - a cross-sectional study.

OBJECTIVE: Hormonal factors have been suggested to contribute to female dominance among subjects with temporomandibular disorders (TMD). Aim of the study was to examine the association of climacteric status with TMD amongst female participants in the Northern Finland Birth Cohort (NFBC) 1966 at 46 years of age. MATERIAL AND METHODS: Among female subjects in NFBC1966, climacteric status was determined based on menstrual anamnesis and measurement of blood follicle-stimulating hormone (FSH) levels. Women with FSH > 25 IU/L and amenorrhoea > 4 months were defined as climacteric (case group, n = 71); women not diagnosed as climacteric were defined as preclimacteric (control group, n = 656). Differences between cases and controls were evaluated on self-reported TMD pain, clinical TMD signs and TMD diagnoses using modified Diagnostic Criteria for TMD (DC/TMD) protocol. Crosstabulation and logistic regression models were used to analyse differences between cases and controls. RESULTS: Compared to preclimacteric women, climacteric women had significantly more often pain on palpation in temporomandibular joints (TMJs) (OR = 2.64, 95% CI 1.12-6.21, p= .026) and more crepitus in TMJs (OR = 2.92, 95% CI 1.13-7.56, p= .027). Degenerative joint disease diagnoses were more common in climacteric than preclimacteric women (OR = 2.27, 95% CI 1.05-4.91, p= .037). Differences were statistically significant after adjusting for confounding factors (body mass index (BMI), smoking, parity). No statistically significant differences in self-reported TMD pain were noted between groups. CONCLUSION: Among females at the age of 46 years, climacterium seems associated with TMD by increasing pain on palpation in TMJs, subjective symptoms, and clinical signs indicating degenerative changes in TMJs when using DC/TMD.

Climacteric status is associated with sexual dysfunction at the age of 46 years: a population-based study.

OBJECTIVE: Increasing age and menopausal transition increase the risk of sexual dysfunction. Sexual dysfunction is common in women experiencing menopause before the age of 40 years, whereas evidence on sexual function in women experiencing menopause in their mid-40s is scarce. We aimed to investigate sexual function in 46-year-old women in relation to their menopausal status. METHODS: This study cross-sectionally evaluated sexual function of women in a prospective population-based Northern Finland Birth Cohort 1966 (NFBC1966). A 46-year follow-up study of NFBC1966 included a broad questionnaire evaluating health, lifestyle, and life situation, as well as menstrual history and sexual function, and blood sampling analysis including follicle stimulating hormone and free androgen index (FAI). The participants were divided into two groups by their menopause status, defined by follicle-stimulating hormone and menstrual history. We performed logistic regression models in which parameters of sexual function were dependent factors and climacteric status, self-reported health, FAI, relationship status, smoking, and education level were independent variables. RESULTS: The study population included 2,661 women. In regression models, more advanced climacteric status was associated with higher frequency and difficulty level of low sexual desire and vaginal dryness (odds ratios with 95% confidence intervals: 2.80 [2.12-3.71], 3.22 [2.43-4.27], 3.83 [2.82-5.20], 3.75 [2.75-5.12], respectively), lower frequency of sexual thoughts (1.34 [1.02-1.75]), and higher frequency of problems with intercourse (2.35 [1.51-3.66]). Lower FAI and poorer health were associated with impaired sexual function. CONCLUSIONS: The current study suggests that women experiencing menopausal transition in their mid-40s are at risk of impaired sexual function.

Women with polycystic ovary syndrome are burdened with multimorbidity and medication use independent of body mass index at late fertile age: A population-based cohort study.

INTRODUCTION: This population-based follow-up study investigated the comorbidities, medication use, and healthcare services among women with polycystic ovary syndrome (PCOS) at age 46 years. MATERIAL AND METHODS: The study population derived from the Northern Finland Birth Cohort 1966 and consisted of women reporting oligo/amenorrhea and hirsutism at age 31 years and/or a PCOS diagnosis by age 46 years (n = 246) and controls without PCOS symptoms or diagnosis (n = 1573), referred to as non-PCOS women. The main outcome measures were self-reported data on symptoms, diagnosed diseases, and medication and healthcare service use at the age of 46 years. RESULTS: Overall morbidity risk was increased by 35% (risk ratio [RR] 1.35, 95% confidence interval [CI] 1.16-1.57) and medication use by 27% [RR 1.27, 95% CI 1.08-1.50) compared with non-PCOS women, and the risk remained after adjusting for body mass index. Diagnoses with increased prevalence in women with PCOS were migraine, hypertension, tendinitis, osteoarthritis, fractures, and endometriosis. PCOS was also associated with autoimmune diseases and recurrent upper respiratory tract infections and symptoms. Interestingly, healthcare service use did not differ between the study groups after adjusting for body mass index. CONCLUSIONS: Women with PCOS are burdened with multimorbidity and higher medication use, independent of body mass index.

52-year follow-up of a birth cohort reveals a high pneumonia incidence among young men.

Background: Knowledge of pneumonia incidence and risk factors in adults is mainly based on clinical studies of selected patient data and registers with ageing populations. Prospective population-based investigations, such as birth cohort studies, are needed to understand pneumonia incidence and risk factors among young and working-age populations. Methods: Northern Finland Birth Cohort (NFBC) 1966 data (n=6750) were analysed for pneumonia incidence and risk factors. Incidence analysis was replicated using data from an independent NFBC 1986 cohort (n=9207). Pneumonia in relation to chronic conditions and lifestyle factors was analysed. Results: A peak with a maximum of 227 pneumonia episodes per 10 000 among men between the ages of 19 and 21 years was found in two independent cohorts. Pneumonia was associated with male sex (relative risk 1.72, 95% CI 1.45-2.04; p<0.001), low educational level (relative risk 2.30, 95% CI 1.72-3.09; p<0.001), smoking (relative risk 1.55, 95% CI 1.31-1.84; p<0.001), asthma (relative risk 2.19, 95% CI 1.73-2.75; p<0.001), cardiovascular diseases (relative risk 2.50, 95% CI 2.04-3.07; p=0.001), kidney diseases (relative risk 4.14, 95% CI 2.81-6.10; p<0.001), rheumatoid arthritis (relative risk 2.69, 95% CI 1.80-4.01; p<0.001), psoriasis (relative risk 2.91, 95% CI 1.92-4.41; p<0.001) and type II diabetes (relative risk 1.80, 95% CI 1.34-2.42; p<0.001). Men with excessive alcohol consumption at age 31 years were at risk of future pneumonia (relative risk 2.40, 95% CI 1.58-3.64; p<0.001). Conclusions: Birth cohort data can reveal novel high-risk subpopulations, such as young males. Our study provides understanding of pneumonia incidence and risk factors among young and working age populations.

Is climacterium by the mid-40s associated with thyroid dysfunction or autoimmunity? A population-based study.

OBJECTIVE: We investigated whether more advanced climacteric stage in the mid-40s is associated with thyroid autoimmunity and dysfunction. METHODS: This cross-sectional cohort study included 2,569 46-year-old women. Thyroid hormone, thyroid peroxidase antibodies, and follicle-stimulating hormone levels were determined. Using menstrual history and follicle-stimulating hormone levels, the participants were divided into climacteric (n = 340) and preclimacteric (n = 2,229) groups. Women diagnosed with premature ovarian insufficiency (menopause by 40 y of age) were excluded. The use of thyroid medication was evaluated from the medication reimbursement register. The prevalence of thyroid medication use, laboratory-based thyroid dysfunction, and thyroid peroxidase antibody positivity was compared between the two groups. The association between climacteric status and thyroid disorders was investigated using a logistic regression model including smoking and thyroid antibody status. RESULTS: At 46 years old, climacteric women used thyroid medication more often than preclimacteric women (9.1% vs 6.1%; P = 0.04). There was no difference in the prevalence of subclinical or clinical hypothyroidism and hyperthyroidism in nonmedicated participants (5.5% vs 5.0%; P = 0.7) or thyroid peroxidase antibody positivity (14.0% vs 15.0%, P = 0.7). In the regression model, being climacteric (OR = 1.6; 95% CI 1.1-2.3; P = 0.02) and antibody positivity (OR 4.9; 95% CI 3.6-6.6; P < 0.001) were associated with a higher prevalence of thyroid dysfunction. CONCLUSIONS: More advanced climacteric stage in the mid-40s was slightly associated with thyroid dysfunction but not thyroid autoimmunity.

Video Summary:http://links.lww.com/MENO/A771 .

Prevalence of oral mucosal normal variations and lesions in a middle-aged population: a Northern Finland Birth Cohort 1966 study.

BACKGROUND: In this cross-sectional study we investigated the oral mucosal changes in a middle-aged Finnish population. We analyzed the prevalence of potentially malignant disorders and the influence of smoking, snuff and alcohol use on the mucosal changes. METHODS: Of the 12,068 members of the NFBC 1966, a total of 1961 participants (16.2%) constituted the study population. Mucosal changes were diagnosed and photographed by seven general dentists, and two specialists re-analyzed all the diagnoses based on the documentation Cross-tabulation with Chi-square tests and logistic regression analysis were used to analyze the data. RESULTS: Of the participants, 10.5% had some mucosal changes, of which 81.8% were diagnosed as oral mucosal lesions (OML) and 18.2% as normal variations. Of the normal variations, the most common were Fordyce granules (1.2%), fissured tongue (1.1%) and geographic tongue (0.9%). The most common OMLs were white lesions (6.5%), of which oral lichen planus (OLP) and lichenoid reactions (OLR), grouped as oral lichenoid diseases, were present in 3.5%, males more often (3.8% vs. 3.1%). OLP was found in 1.5% of all participants, females more often (1.8% vs. 1.2%), while OLR was more common in males (2.7% vs. 1.3%). Leukoplakia was identified in 0.5% of the population; twice more often in males (0.6% vs. 0.3%). Erythroplakia was not found. Current smokers had higher risk for oral mucosal changes than former or non-smokers (OR 3.0, 95% CI 2.11-4.28), and snuff, used occasionally or regularly, also raised the risk (OR 2.6, 95% CI 1.48-4.70). CONCLUSIONS: In the middle-aged northern Finland population, 4% of OMLs were potentially malignant disorders, including OLR (2%), OLP (1.5%) and leukoplakia (0.5%). In particular, smoking and snuff use increased the risk for having any oral mucosa changes.

Effects of Estrogen Level, Dietary Loading, and Aging on Types I, II, and X Collagen Expression and Structure of Rat Mandibular Condylar Cartilage.

AIMS: To investigate how estrogen level, dietary loading, and aging affect cartilage structure and the expression of major collagens (types I, II, and X) in rat mandibular condylar cartilage (MCC). METHODS: A total of 96 outbred Sprague Dawley female rats were randomly divided into two groups by ovariectomy (OVX) at 7 weeks old. One week later, the rats in each group were further divided into three subgroups on the basis of food hardness: hard food (diet board), normal food (pellet), and soft food (powder). The rats were sacrificed at the age of 5 or 14 months. The thickness of the fibrous, proliferative, and chondroblastic layers of the mandibular condylar cartilage were measured after toluidine blue staining. Immunohistochemical analysis was performed to evaluate the expression levels of types I, II, and X collagen. A linear regression model was used to investigate the main factors affecting changes in thickness and collagen expression. RESULTS: The expression levels of types II and X collagen were decreased by ovarian estrogen deficiency and increased by dietary loading. Increased dietary loading was the main factor affecting an increase in thickness of the cartilage layers, while aging was the main factor affecting a decrease in thickness of the fibrous layer. A significant age-related increase was found in the expression of type I collagen. There was some degree of interaction between aging and dietary loading that affected the thickness of the chondroblastic layer and the expression of type X collagen. CONCLUSION: The physiologic level of estrogen plays a role in MCC development by promoting the expression of types II and X collagen. Dietary loading is essential to increase the expression of types II and X collagen, as well as the thickness of cellular layers, to maintain the integrity of the MCC. Aging seems to reduce the ability of the MCC to withstand occlusal loading.

Onset of the climacteric phase by the mid-forties associated with impaired insulin sensitivity: a birth cohort study.

OBJECTIVE: To investigate whether the early-onset menopausal transition is associated with deteriorated glucose tolerance in women in their mid-forties. METHODS: A cross-sectional analysis of a cohort study including 2,632 women of the Northern Finland Birth Cohort 1966. The participants were divided into two groups by their menstrual history and follicle-stimulating hormone values at age 46: climacteric and preclimacteric women. Glucose and insulin parameters, as well as mathematical indices derived from them to evaluate insulin sensitivity, were compared between the groups. The results were adjusted for measured body mass index and smoking. The possible effect of hormone therapy was investigated in subanalyses excluding hormone therapy users. RESULTS: Climacteric women (n = 379) were more often current smokers at age 46 (P = 0.008), and their body mass indices increased more from 31 to 46 years (P = 0.013), compared to preclimacteric women (n = 2,253). In a multivariable generalized linear model, being climacteric at age 46 was associated with several findings suggesting decreased insulin sensitivity: increased glycated hemoglobin (P < 0.001), 2-hour oral glucose tolerance test 30- and 60-minute insulin (P = 0.040 and 0.006, respectively), and area under the insulin curve (P = 0.005). Being climacteric also was associated with a decreased the McAuley (P = 0.024) and Belfiore indices (P = 0.027) and glucose tolerance test 60-minute glucose (P = 0.015). In subanalyses excluding hormone therapy users (n = 94), the results did not change significantly. CONCLUSIONS: Earlier onset of climacteric transition is associated with impaired insulin sensitivity in middle-aged women.

Video Summary:http://links.lww.com/MENO/A648.

Vitamin D Levels in Women with Polycystic Ovary Syndrome: A Population-Based Study.

BACKGROUND: Conflicting evidence supports a role for vitamin D in women with reproductive disorders such as polycystic ovary syndrome (PCOS) but studies on large, unselected populations have been lacking. METHODS: We conducted a general population-based study from the prospective Northern Finland Birth Cohort 1966 (NFBC1966). Serum 25-hydroksyvitamin D (25(OH)D) levels were evaluated in women with self-reported PCOS (n = 280) versus non-symptomatic controls (n = 1573) at the age of 31 with wide range of endocrine and metabolic confounders. RESULTS: The levels of 25(OH)D were similar among women with and without self-reported PCOS (50.35 vs. 48.30 nmol/L, p = 0.051). Women with self-reported PCOS presented with a higher body mass index (BMI), increased insulin resistance, and low-grade inflammation and testosterone levels compared to controls. The adjusted linear regression model showed a positive association between total 25(OH)D levels in self-reported PCOS (ß = 2.46, 95% confidence interval (CI) 0.84 to 4.08, p = 0.003). The result remained after adjustment for BMI, testosterone, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hs-CRP) levels. CONCLUSION: In this population-based setting, PCOS was associated with higher vitamin D levels when adjusting for confounding factors, without distinct beneficial effects on metabolic derangements.

Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.

Erosive tooth wear and use of psychoactive substances among Finnish prisoners.

BACKGROUND: The aim of the study was to evaluate the prevalence and severity of erosive tooth wear (ETW) and its association with dental caries and the use of psychoactive substances among Finnish prisoners. METHODS: One hundred voluntary prisoners (90.9%) from the Pelso Prison participated in this cross-sectional clinical study between September 2014 and February 2015. Fifty prisoners were also interviewed using the one-on-one interviewing technique for their background factors and use of psychoactive substances. Basic Erosive Index (BEWE) (0-18) was used to measure erosive tooth wear. Decayed (D), missing (M), filled (F) and the number of remaining teeth (T) and DMFT were reported. The association between the different variables was tested and analysed by using cross tabulation. To test the association between the variables a logistic regression analysis was conducted. RESULTS: Almost all (90%) of the subjects had need for preventive and operative treatment for ETW. In addition, one in five (19%) suffered from severe erosive tooth wear. The use of psychoactive substances and pharmaceuticals is common, yet no association with ETW was found. Smoking and alcohol consumption were more common among younger prisoners than the older ones. There is an increased risk for ETW among older prisoners and major alcohol consumers. Past caries experience was associated with dental erosion. CONCLUSIONS: Erosive tooth wear is common among Finnish prisoners in their thirties. ETW is associated with dental caries and daily alcohol consumption.