Polycystic ovary syndrome (PCOS) 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 = 1 556) in the Northern Finland Birth Cohort 1966. MAIN OUTCOME MEASURES: National register data on diagnosed diseases (ICD-8-10) and medication use (ATC) until the age of 50. RESULTS: Women with PCOS had a 26% higher risk for any registered diagnosis (RR: 1.26 [1.09-1.46]) and a 24% higher risk for medication use (RR: 1.24 [1.05-1.46]) compared to non-PCOS women, even after adjusting for several confounders. Several main ICD categories were more prevalent among women with PCOS versus non-PCOS controls, e.g., 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 BMI ≥ 25gk/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, e.g., medications related to the alimentary tract and metabolism, the cardiovascular system, genito-urinary 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.

Women with a history of gestational diabetes mellitus present an accumulation of cardiovascular risk factors at age 46-A birth cohort study.

INTRODUCTION: The incidence of gestational diabetes mellitus (GDM) is globally increasing, and it has been associated with later type 2 diabetes, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, long-term population-based studies investigating common CVD risk factors years after pregnancy are lacking. To evaluate the future mortality and morbidity in cardiovascular and metabolic diseases, we conducted a thorough investigation of midlife risk factors in women with and without previous GDM. MATERIAL AND METHODS: A prospective population-based cohort study was conducted of 3173 parous women from the Northern Finland Birth Cohort, 1966. Subjects were obtained from the national register or patient records. Those with a GDM diagnosis formed the GDM cohort (n = 271), and those without a previous GDM diagnosis formed the control cohort (n = 2902). Clinical examinations were performed on participants at the age of 46 and included anthropometric measurements, oral glucose tolerance test (OGTT), biochemical measurements, and cardiovascular assessment. RESULTS: At the age of 46, women in the GDM cohort had a higher body mass index (BMI, 29.0 kg/m2 vs 26.3 kg/m2, p < 0.001) and greater waist circumference (94.1 cm vs 86.5 cm, p < 0.001) than the control cohort. In the GDM cohort, a higher incidence of impaired glucose tolerance (12.6% vs 7.3%, p = 0.002), more previously diagnosed and OGTT-detected type 2 diabetes (23.3% vs 3.9%, p < 0.001), lower high-density lipoprotein (1.53 mmol/L vs 1.67 mmol/L, p = 0.011), higher triglycerides (1.26 mmol/L vs 1.05 mmol/L, p = 0.002) and a higher fatty liver index (6.82 vs 2.47, p < 0.001), were observed even after adjusting for BMI, polycystic ovary syndrome, parity, level of education, physical activity, smoking, and alcohol consumption. The women in the GDM cohort also had more MetS (42.6% vs 21.9%, p < 0.001) and higher risk scores for CVD and fatal events (Framingham 4.95 vs 3.60, p < 0.001; FINRISK 1.71 vs 1.08, p < 0.001). CONCLUSIONS: Women with a previous diagnosis of GDM exhibit more risk factors for CVD in midlife and are at a higher risk for cardiovascular events later in life.

Low testosterone at age 31 associates with maternal obesity and higher body mass index from childhood until age 46: A birth cohort study.

BACKGROUND: Low testosterone (T) levels in men associate with increased risks of obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases. However, most studies are cross-sectional with follow-up-time < 10 years, and data on early growth are limited. OBJECTIVE: To compare prenatal factors and body mass index (BMI) development from birth to age 46 in relation to low T at age 31. MATERIALS AND METHODS: Men with low T (T < 12.1 nmol/L, n = 132) and men with normal T at age 31 (n = 2561) were derived from the Northern Finland Birth Cohort 1966. Prenatal factors, longitudinal weight and height data from birth to age 14, and cross-sectional weight and height data at ages 31 and 46, and waist-hip-ratio (WHR) and T levels at age 31 were analyzed. Longitudinal modeling and timing of adiposity rebound (AR, second BMI rise at age 5-7 years) were calculated from fitted BMI curves. Results were adjusted for mother's pre-pregnancy BMI and smoking status, birth weight for gestational age, alcohol consumption, education level, smoking status, and WHR at age 31. RESULTS: Neither gestational age nor birth weight was associated with low T at age 31; however, maternal obesity during gestation was more prevalent among men with low T (9.8% vs. 3.5%, adjusted aOR: 2.43 [1.19-4.98]). Men with low T had earlier AR (5.28 vs. 5.82, aOR: 0.73 [0.56-0.94]) and higher BMI (p < 0.001) from AR onward until age 46. Men with both early AR and low T had the highest BMI from AR onward. CONCLUSIONS: In men, maternal obesity and early weight gain associate with lower T levels at age 31, independently of adulthood abdominal obesity. Given the well-known health risks related to obesity, and the rising prevalence of maternal obesity, the results of the present study emphasize the importance of preventing obesity that may also affect the later reproductive health of the offspring.

High-sensitivity troponin-T levels and associated health conditions in 3146 women aged 46.

OBJECTIVE: The aim of the study was to investigate are there associations between common female sex-specific health conditions (oligo/amenorrhea, hyperandrogenism, menopause and polycystic ovary syndrome [PCOS]) and high-sensitivity troponin-T (hs-TnT) levels. METHODS: Cross-sectional and longitudinal analyses of a general population-based prospective cohort study were performed. The hs-TnT levels of 3146 women aged 46 were measured using an Elecsys® Troponin T high-sensitivity assay. Median hs-TnT levels and 25 and 75 percentiles of the cases and controls were compared. Also, a logistic regression analysis using a binary outcome - undetectable hs-TnT (< 3.0 ng/L) versus detectable hs-TnT (≥ 3.0 ng/L) - was performed. RESULTS: Women with oligo/amenorrhea at age 31 had significantly higher hs-TnT levels at age 46 than women without oligo/amenorrhea (4.06 [3.59; 4.86] vs 3.98 [3.44; 4.71] ng/L, p = .042). Menopausal women had significantly higher hs-TnT levels than premenopausal women (4.15 [3.54; 4.91] vs 3.95 [3.45; 4.68] ng/L, p = .012) at age 46. Women with PCOS or hyperandrogenism had comparable hs-TnT levels with their controls. In the adjusted logistic regression analysis, oligo/amenorrhea (odds ratio [OR] = 1.52 [0.90-2.57]), hyperandrogenism (OR = 1.20 [0.75-1.92]), PCOS (OR = 1.51 [0.81-2.84]) and menopause (OR = 1.05 [0.63-1.74]) were not significantly associated with detectable hs-TnT. CONCLUSIONS: This study was the first to investigate how oligo/amenorrhea, hyperandrogenism, PCOS and menopause are associated with hs-TnT. Although women with oligo/amenorrhea and menopause had higher hs-TnT levels than women without these conditions, the difference was small. Larger studies are required to better understand the effects of oligo/amenorrhea on cardiovascular health.

No previous studies have investigated the association between common female sex-specific health conditions, such as oligo/amenorrhea, hyperandrogenism and PCOS, and hs-TnT levels. Only one prior study has investigated the association between menopause and hs-TnT levels.Hs-TnT levels were significantly higher in women with oligo/amenorrhea and relatively early menopause at age 46 than women without these conditions, whereas women with hyperandrogenism or PCOS and their controls have comparable hs-TnT levels.The effect of oligo/amenorrhea on cardiovascular health should be further investigated. A simple question about the presence of oligo/amenorrhea might identify women at increased risk of cardiovascular disease.

Serum ceramides in early pregnancy as predictors of gestational diabetes.

Ceramides contribute to the development of type 2 diabetes but it is uncertain whether they predict gestational diabetes (GDM). In this multicentre case-control study including 1040 women with GDM and 958 non-diabetic controls, early pregnancy (mean 10.7 gestational weeks) concentrations of four ceramides-Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)-were determined by a validated mass-spectrometric method from biobanked serum samples. Traditional lipids including total cholesterol, LDL, HDL and triglycerides were measured. Logistic and linear regression and the LASSO logistic regression were used to analyse lipids and clinical risk factors in the prediction of GDM. The concentrations of four targeted ceramides and total cholesterol, LDL and triglycerides were higher and HDL was lower among women with subsequent GDM than among controls. After adjustments, Cer(d18:1/24:0), triglycerides and LDL were independent predictors of GDM, women in their highest quartile had 1.44-fold (95% CI 1.07-1.95), 2.17-fold (95% CI 1.57-3.00) and 1.63-fold (95% CI 1.19-2.24) odds for GDM when compared to their lowest quartiles, respectively. In the LASSO regression modelling ceramides did not appear to markedly improve the predictive performance for GDM alongside with clinical risk factors and triglycerides. However, their adverse alterations highlight the extent of metabolic disturbances involved in GDM.

Former long-term use of combined hormonal contraception and glucose metabolism disorders in perimenopausal women: A prospective, population-based cohort study.

INTRODUCTION: Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial. MATERIAL AND METHODS: This was a prospective, longitudinal birth cohort study with long-term follow-up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2-h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin-only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253). RESULTS: Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6-9.2) but not of type 2 diabetes mellitus. Former progestin-only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol-lowering medication. CONCLUSIONS: Former long-term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.

Women with PCOS have an increased risk for cardiovascular disease regardless of diagnostic criteria-a prospective population-based cohort study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is associated with many cardiovascular disease (CVD) risk factors, such as obesity, type 2 diabetes mellitus and hypertension. However, it remains debatable whether the presence of multiple CVD risk factors translates to increased CVD events. DESIGN: A prospective, population-based Northern Finland Birth Cohort 1966. METHODS: Individuals with an expected date of birth in 1966 in Northern Finland have been followed from birth. Women in the cohort were classified as having PCOS according to either the National Institute of Health (NIH) criteria (n = 144) or the Rotterdam criteria (n = 386) at age 31, and they were compared to women without any PCOS features. The study population was re-examined at age 46, and the incidence of major adverse cardiovascular events (MACE), including myocardial infarction (MI), stroke, heart failure and cardiovascular mortality, was recorded up to age 53. RESULTS: During the 22-year follow-up, both women with NIH-PCOS and women with Rotterdam-PCOS had a significantly higher risk for cardiovascular events than control women. The BMI-adjusted hazard ratio (HR) for MACE in the Rotterdam-PCOS group and the NIH-PCOS group was 2.33 (1.26-4.30) and 2.47 (1.18-5.17), respectively. The cumulative hazard curves in both diagnostic categories began to diverge at age 35. Regarding the individual CVD endpoints, MI was significantly more prevalent in both women with NIH-PCOS (P = .010) and women with Rotterdam-PCOS (P = .019), when compared to control women. CONCLUSIONS: PCOS should be considered a significant risk factor for CVD. Future follow-up will show how the risk of CVD events develops after menopausal age.

Vitamin D Status in Women with a History of Infertility and Decreased Fecundability: A Population-Based Study.

BACKGROUND: Infertility and fecundability problems have been linked with lower 25-hydroxyvitamin D (25(OH)D) concentrations, but studies conducted with small, heterogenous or selected populations have shown inconsistent results. METHODS: This study included women at age 31 from prospective population-based Northern Finland Birth Cohort 1966. Serum 25(OH)D concentrations were evaluated between women with or without previous infertility examinations or treatments (infertility group, n = 375, reference group, n = 2051) and time to pregnancy (TTP) of over 12 months (decreased fecundability group, n = 338) with a wide range of confounders. Furthermore, 25(OH)D concentrations were also compared among reproductive outcomes. RESULTS: The mean 25(OH)D concentration was lower and 25(OH)D < 30 nmol/L was more frequent in women with a history of infertility compared to reference group. Moreover, 25(OH)D > 75 nmol/L was more frequent in the reference group. The mean 25(OH)D concentration was lower in women who had had multiple miscarriages. Both history of infertility (ß = -2.7, 95% confidence interval (CI) -4.6, -0.7) and decreased fecundability associated with lower 25(OH)D concentration (ß = -4.1, 95% CI -7.4, -0.8) after adjustments. In conclusion, this population-based study demonstrated that previous infertility and decreased fecundability were associated with lower 25(OH)D.

AMH as part of the diagnostic PCOS workup in large epidemiological studies.

OBJECTIVES: Previous studies have shown good correlation between polycystic ovarian morphology (PCOM) and serum anti-Müllerian hormone (AMH) levels. We evaluated the utility of AMH as a surrogate for PCOM as a part of the polycystic ovary syndrome (PCOS) diagnosis by describing how the use of different AMH cut-off values would change the prevalence of PCOS. METHODS: A general population-based birth cohort study. Anti-Müllerian hormone concentrations were measured from serum samples taken at age 31 years (n = 2917) using the electrochemiluminescence immunoassay (Elecsys). Anti-Müllerian hormone data were combined with data on oligo/amenorrhoea and hyperandrogenism to identify women with PCOS. RESULTS: The addition of AMH as a surrogate marker for PCOM increased the number of women fulfilling at least two PCOS features in accordance with the Rotterdam criteria. The prevalence of PCOS was 5.9% when using the AMH cut-off based on the 97.5% quartile (10.35 ng/mL) and 13.6% when using the recently proposed cut-off of 3.2 ng/mL. When using the latter cut-off value, the distribution of PCOS phenotypes A, B, C, and D was 23.9%, 4.7%, 36.6%, and 34.8%, respectively. Compared with the controls, all PCOS groups with different AMH concentration cut-offs showed significantly elevated testosterone (T), free androgen index (FAI), luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) ratio, body mass index (BMI), waist circumference, and homoeostatic model assessment of insulin resistance (HOMA-IR) values, as well as significantly decreased sex hormone-binding globulin (SHBG) values. CONCLUSIONS: Anti-Müllerian hormone could be useful surrogate for PCOM in large data sets, where transvaginal ultrasound is not feasible, to aid the capturing of women with typical PCOS characteristics. Anti-Müllerian hormone measurement from archived samples enables retrospective PCOS diagnosis when combined with oligo/amenorrhoea or hyperandrogenism.

Oral and Vaginal Hormonal Contraceptives Induce Similar Unfavorable Metabolic Effects in Women with PCOS: A Randomized Controlled Trial.

This clinical trial aims to compare hormonal and metabolic changes after a 9-week continuous use of oral or vaginal combined hormonal contraceptives (CHCs) in women with polycystic ovary syndrome (PCOS). We recruited 24 women with PCOS and randomized them to use either combined oral (COC, n = 13) or vaginal (CVC, n = 11) contraception. At baseline and 9 weeks, blood samples were collected and a 2 h glucose tolerance test (OGTT) was performed to evaluate hormonal and metabolic outcomes. After treatment, serum sex hormone binding globulin (SHBG) levels increased (p < 0.001 for both groups) and the free androgen index (FAI) decreased in both study groups (COC p < 0.001; CVC p = 0.007). OGTT glucose levels at 60 min (p = 0.011) and AUCglucose (p = 0.018) increased in the CVC group. Fasting insulin levels (p = 0.037) increased in the COC group, and insulin levels at 120 min increased in both groups (COC p = 0.004; CVC p = 0.042). There was a significant increase in triglyceride (p < 0.001) and hs-CRP (p = 0.032) levels in the CVC group. Both oral and vaginal CHCs decreased androgenicity and tended to promote insulin resistance in PCOS women. Larger and longer studies are needed to compare the metabolic effects of different administration routes of CHCs on women with PCOS.

Polycystic ovary syndrome is associated with weight-loss attempts and perception of overweight independent of BMI: a population-based cohort study.

OBJECTIVE: Up to 70% of women with polycystic ovary syndrome (PCOS) have pre-obesity or obesity. The aim of this study was to investigate whether women with PCOS have more weight-loss attempts than women without PCOS, regardless of BMI. Moreover, women's weight perceptions in relation to previous weight-loss attempts were evaluated. METHODS: A population-based birth cohort study included women with (n = 278) and without PCOS (control individuals, n = 1560) who were examined at ages 31 and 46 years with questionnaires and clinical examinations. RESULTS: Women with PCOS had more weight-loss attempts compared with control individuals at age 31 (47% vs. 34%, p < 0.001) and 46 years (63% vs. 47%, p < 0.001). At age 46 years, PCOS was associated with multiple weight-loss attempts in the adjusted model (odds ratio: 1.43 [95% CI: 1.00-2.03], p = 0.05). The perception of having overweight was more prevalent in those with PCOS, even among participants with normal weight, at age 31 (PCOS 47% vs. control 34%, p = 0.014) and 46 years (PCOS 60% vs. control 39%, p = 0.001). CONCLUSIONS: Women with PCOS were more likely to have experienced multiple weight-loss attempts and a perception of having overweight compared with control individuals, regardless of obesity status.

Associations of low sex hormone-binding globulin and androgen excess in early pregnancy with fasting and post-prandial hyperglycaemia, gestational diabetes, and its severity.

AIMS: We studied whether androgen excess and low sex hormone-binding globulin (SHBG) measured in early pregnancy are independently associated with fasting and post-prandial hyperglycaemia, gestational diabetes (GDM), and its severity. MATERIALS AND METHODS: This nationwide case-control study included 1045 women with GDM and 963 non-diabetic pregnant controls. We measured testosterone (T) and SHBG from biobanked serum samples (mean 10.7 gestational weeks) and calculated the free androgen index (FAI). We first studied their associations with GDM and secondly with the type of hyperglycaemia (fasting, 1 and 2 h glucose concentrations during the oral glucose tolerance test), early-onset GDM (<20 gestational weeks) and the need for anti-diabetic medication. RESULTS: After adjustments for gestational weeks at sampling, pre-pregnancy BMI, and age, women with GDM had 3.7% (95% CI 0.1%-7.3%) lower SHBG levels, 3.1% (95% CI 0.1%-6.2%) higher T levels, and 4.6% (95% CI 1.9%-7.3%) higher FAI levels than controls. SHBG was inversely associated with fasting glucose, whereas higher FAI and T were associated with higher post-prandial glucose concentrations. Women with early-onset GDM had 6.7% (95% CI 0.7%-12.7%) lower SHBG levels and women who needed insulin for fasting hyperglycaemia 8.7% (95% CI 1.8%-14.8%) lower SHBG levels than other women with GDM. CONCLUSIONS: Lower SHBG levels were associated especially with early-onset GDM, higher fasting glucose and insulin treatment, whereas androgen excess was associated with higher post-prandial glucose values. Thus, a low SHBG level may reflect the degree of existing insulin resistance, while androgen excess might impair post-prandial insulin secretion.

An optimal growth pattern during pregnancy and early childhood associates with better fertility in men.

Objective: This study aimed to evaluate the association between birth weight (BW), childhood and adolescent BMI, with reproductive capacity in men. Design: A prospective, population-based cohort study (Northern Finland birth cohort 1966). Methods: Around 6196 men born in 1966 were followed from birth to age 50 years. Weight and height were measured repeatedly by professionals. Reproductive capacity (infertility assessment, male factor infertility and infertility treatment by age 46 years) was evaluated by questionnaires at ages 31 and 46 years. The number of children by the age of 50 years was recovered from registers. After excluding the men who reported never having attempted to have children or not answering the question at age 31 or 46 years (n = 2041), 4128 men were included in the final study population. Results were adjusted for BW, BW for gestational age (GA), mother's smoking status, marital status, educational level and smoking status. Results: Being small for GA (10.5% vs 8.2%, P = 0.012) or having a lower BW (3495 g vs 3548 g, P = 0.003) were associated with childlessness. The association was however no longer significant after adjusting for marital status. Being underweight in early childhood was associated with an increased risk of infertility assessment (adjusted, aOR: 2.04(1.07-3.81)) and childlessness (aOR: 1.47(1.01-2.17)) compared to the normal weight group. Conversely, overweight or obesity in early childhood was associated with a decreased risk of infertility assessment (aOR: 0.60 (0.41-0.87)), treatment (aOR: 0.42 (0.25-0.70)) and male factor infertility (aOR: 0.45 (0.21-0.97)). BMI in mid-childhood or puberty had no association with infertility or childlessness. Conclusion: In boys, an optimal growth trajectory during pregnancy and early childhood seems to be very important for life-long fertility.

Polycystic ovary syndrome and leukocyte telomere length: cross-sectional and longitudinal changes.

Objective: Telomeres are DNA-protein complexes that protect chromosome ends from DNA damage and are surrogate biomarkers of cellular aging. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardiometabolic risk factors. Polycystic ovary syndrome (PCOS), the most common gynecological endocrine disorder, is associated with inflammation and oxidative stress, both factors associated with accelerated telomere attrition. We therefore hypothesized that LTL would be shorter and decrease more rapidly in women with PCOS in comparison to a control population. Design: This is a population-based cohort study comprising women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (age 31, n = 190; age 46, n = 207) and referent women (age 31, n = 1054; age 46, n = 1324) with data on LTL. Methods: The association between LTL and PCOS at ages 31 and 46 was analyzed by linear regression models adjusted for BMI, smoking, alcohol consumption and socioeconomic status at the corresponding age. Results: Women with PCOS had similar mean LTL at ages 31 and 46 (P > 0.4 for both). The mean LTL change between ages 31 and 46 did not differ between groups (P = 0.19). However, we observed a significant LTL attrition between ages 31 and 46 in the reference population (P < 0.001), but not in women with PCOS (P = 0.96). Conclusions: This finding may suggest a difference in the LTL attrition rate in women with PCOS, an unexpected finding that might affect their risk of age-related disease. Further research is needed to clarify the underlying mechanisms.

Women with polycystic ovary syndrome have poorer work ability and higher disability retirement rate at midlife: a Northern Finland Birth Cohort 1966 study.

Objective: Polycystic ovary syndrome (PCOS) presents with multiple comorbidities potentially affecting function. This was the first general population-based study to evaluate work ability, participation in working life, and disability retirement in middle-aged women with and without PCOS. Design: This is a cohort study. Methods: Women with PCOS (n = 280) and women without PCOS symptoms or diagnosis (n = 1573) were identified in the Northern Finland Birth Cohort in 1966 and were evaluated for self-rated work ability and potential confounders at age 46. Next, incidence rate ratios (IRRs) for disability and unemployment days were extracted from national registers during a prospective 2-year follow-up. Lastly, we assessed hazard ratios (HRs) for disability retirement between 16 and 52 years of age from national registers. Results: The women with PCOS reported poorer ability to work at age 46, especially due to poorer health. During the 2-year follow-up period, the affected women gained on average an additional month of disability and unemployment days, corresponding to an approximately 25% higher risk for both disability (IRR (95% CI): 1.25 (1.22-1.27)) and unemployment days (IRR (95% CI): 1.26 (1.23-1.28)) in models adjusted for health and socioeconomic factors. Lastly, we found a two-fold higher cumulative risk for disability retirement by age 52 compared to non-PCOS women (HR (95% CI): 1.98 (1.40-2.80)), which remained after adjusting for confounding factors (aHR (95% CI): 1.55 (1.01-2.38)). Conclusions: PCOS is associated with lower participation in working life already in midlife. Acknowledging PCOS-related multimorbidity, concerted efforts are needed to support sustainable careers for women with PCOS.

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.

Metformin in pregnancy and risk of adverse long-term outcomes: a register-based cohort study.

INTRODUCTION: This study aimed to investigate if maternal pregnancy exposure to metformin is associated with increased risk of long-term and short-term adverse outcomes in the child. RESEARCH DESIGN AND METHODS : This register-based cohort study from Finland included singleton children born 2004-2016 with maternal pregnancy exposure to metformin or insulin (excluding maternal type 1 diabetes): metformin only (n=3967), insulin only (n=5273) and combination treatment (metformin and insulin; n=889). The primary outcomes were long-term offspring obesity, hypoglycemia, hyperglycemia, diabetes, hypertension, polycystic ovary syndrome, and challenges in motor-social development. In a sensitivity analysis, the primary outcomes were investigated only among children with maternal gestational diabetes. Secondary outcomes were adverse outcomes at birth. Analyses were conducted using inverse- probability of treatment weighting (IPTW), with insulin as reference. RESULTS  : Exposure to metformin or combination treatment versus insulin was not associated with increased risk of long-term outcomes in the main or sensitivity analyses. Among the secondary outcomes, increased risk of small for gestational age (SGA) was observed for metformin (IPTW-weighted OR 1.65, 95% CI 1.16 to 2.34); increased risk of large for gestational age, preterm birth and hypoglycemia was observed for combination treatment. No increased risk was observed for neonatal mortality, hyperglycemia, or major congenital anomalies. CONCLUSIONS : This study found no increased long-term risk associated with pregnancy exposure to metformin (alone or in combination with insulin), compared with insulin. The increased risk of SGA associated with metformin versus insulin suggests caution in pregnancies with at-risk fetal undernutrition. The increased risks of adverse outcomes at birth associated with combination treatment may reflect confounding by indication or severity.

A population-based follow-up study shows high psychosis risk in women with PCOS.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to 18% of women. Besides metabolic and fertility aspects, attention has lately been directed towards the detrimental effect of PCOS on psychological health. The objective of the study was to investigate whether women with PCOS are at higher risk for psychotic disorders. The study population derives from the Northern Finland Birth Cohort 1966 (N = 5889 women). The women with PCOS were identified by two simple questions on oligo-amenorrhea and hirsutism at age 31. Women reporting both symptoms were considered PCOS (N = 124) and asymptomatic women as controls (N = 2145). The diagnosis of psychosis was traced using multiple national registers up to the year 2016. Symptoms of psychopathology were identified using validated questionnaires at age 31. Women with PCOS showed an increased risk for any psychosis by age 50 (HR [95% CI] 2.99, [1.52-5.82]). Also, the risk for psychosis after age 31 was increased (HR 2.68 [1.21-5.92]). The results did not change after adjusting for parental history of psychosis, nor were they explained by body mass index or hyperandrogenism at adulthood. The scales of psychopathology differed between women with PCOS and non-PCOS controls showing more psychopathologies among the affected women. PCOS cases were found to be at a three-fold risk for psychosis, and they had increased psychopathological symptoms. PCOS should be taken into consideration when treating women in psychiatric care. More studies are required to further assess the relationship between PCOS and psychotic diseases.