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

Population-based data at ages 31 and 46 show decreased HRQoL and life satisfaction in women with PCOS symptoms.

CONTEXT: Polycystic ovary syndrome (PCOS) is associated with decreased health-related quality of life (HRQoL), but longitudinal data beyond the reproductive years are lacking, and the impact of isolated PCOS symptoms is unclear. OBJECTIVE: To study generic HRQoL using 15D, life satisfaction, and self-reported health status in women with PCOS symptoms at ages 31 and 46yr. DESIGN: A longitudinal assessment using the Northern Finland Birth Cohort 1966. SETTING: General community. PARTICIPANTS: The 15D data were available for women reporting isolated oligomenorrhea (OA;at age 31yr:214 and 46yr: 211), isolated hirsutism (H; 31yr:211 and 46yr:216), OA+H (PCOS; 31yr:74 and 46yr:75), or no PCOS symptoms (controls; 31yr:1382 and 46yr:1412). Data for life satisfaction and current health status were available for OA (31yr:329 and 46yr:247), H (31yr:323 and 46yr:238), PCOS (31yr:125 and 46yr:86), control (31yr:2182 and 46yr:1613) groups. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): 15D HRQoL, questionnaires on life satisfaction, and self-reported health status. RESULTS: HRQoL was lower at ages 31 and 46 in women with PCOS or H compared with the controls. PCOS was an independent risk factor for low HRQoL, and the decrease in HRQoL in PCOS was comparable to that of women with other chronic conditions, like asthma, migraine, rheumatoid arthritis, and depression. The risk for low HRQoL in PCOS remained significant after adjusting for BMI, hyperandrogenism, and socioeconomic status. Mental distress was the strongest contributing factor to HRQoL. PCOS was also associated with a risk for low life satisfaction and a 4-fold risk for reporting a poor health status. CONCLUSIONS: Women with PCOS present with low HRQoL, decreased life satisfaction, and a poorer self-reported health status up to their late reproductive years. Assessments and interventions aiming to improve HRQoL in PCOS should be targeted beyond fertile age

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

Peer reviewe

BMI in childhood and adolescence is associated with impaired reproductive function-a population-based cohort study from birth to age 50 years

Peer reviewe

The Gut Microbiome in Polycystic Ovary Syndrome (PCOS) and its Association with Metabolic Traits

This work was funded by Estonian Research Council grants PUT 1371 (to E.O.), EMBO Installation grant 3573 (to E.O.) … E.O. was supported by European Regional Development Fund Project No. 15-0012 GENTRANSMED and Estonian Center of Genomics/Roadmap II project No 16-0125. S.A. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE (SAF2017-87526-R); and by FEDER/Junta de Andalucía-Consejería de Economía y Conocimiento: MENDO (B-CTS-500-UGR18).Purpose: Despite gut microbiome being widely studied in metabolic diseases, its role in polycystic ovary syndrome (PCOS) has been scarcely investigated. The aim of our study was to test for possible associations between gut microbiome and PCOS in late fertile age women and investigate whether changes in the gut microbiome correlate with PCOS-related metabolic parameters. Methods: We compared the 16S rRNA sequenced gut microbiome of 102 PCOS women with 201 age- and body mass index (BMI) matched non-PCOS women. Clinical and biochemical characteristics of the participants were assessed at ages 31 and 46 and analyzed in the context of gut microbiome data at the age of 46. Results: Bacterial diversity indices did not differ significantly between PCOS and controls. We identified four genera whose balance helps to differentiate between PCOS and non-PCOS. In the whole cohort, the abundance of two genera from the order Clostridiales was correlated with several PCOS-related markers. When investigating the gut microbiome composition in PCOS women with different BMI and glucose tolerance groups, prediabetic PCOS women had significantly lower alpha diversity and markedly increased abundance of genus Dorea compared to women with normal glucose tolerance. Conclusions: Our data indicate that PCOS and non-PCOS women at late fertile age with similar BMI do not signficantly differ in gut microbiota. However, there are significant microbial changes in PCOS individuals depending on their metabolic health. Further studies are needed in order to further understand these changes in more detail.Estonian Research Council grants PUT 1371EMBO Installation grant 3573European Regional Development Fund Project No. 15-0012 GENTRANSMEDEstonian Center of Genomics/Roadmap II project No 16-0125Spanish Ministry of Economy, Industry and Competitiveness (MINECO) European Regional Development Fund (FEDER) RYC-2016-21199 and ENDORE (SAF2017-87526-R)FEDER/Junta de Andalucía-Consejería de Economía y Conocimiento: MENDO (B-CTS-500-UGR18

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 ageing. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardio-metabolic 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 Population-based cohort study: women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (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 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

Awareness of polycystic ovary syndrome among obstetrician-gynecologists and endocrinologists in Northern Europe

cited By 0Peer reviewe

Anti-Mullerian hormone: correlation with testosterone and oligo- or amenorrhoea in female adolescence in a population-based cohort study

Study questions: Can serum anti-Müllerian hormone (AMH) levels measured in female adolescents predict polycystic ovary syndrome (PCOS)-associated features in adolescence and early adulthood? Summary answer: AMH levels associated well with PCOS-associated features (such as testosterone levels and oligoamenorrhoea) in adolescence, but was not an ideal marker to predict PCOS-associated features in early adulthood. What is known already: Several studies have reported that there is a strong correlation between antral follicle count and serum AMH levels and that women with PCOS/PCO have significantly higher serum AMH levels than women with normal ovaries. Other studies have reported an association between AMH serum levels and hyperandrogenism in adolescence, but none has prospectively assessed AMH as a risk predictor for developing features of PCOS during adulthood. Study design, size, duration: A subset of 400 girls was selected from the prospective population-based Northern Finland Birth Cohort 1986 (n = 4567 at age 16 and n = 4503 at age 26). The population has been followed from 1986 to the present. Participants/material, setting, methods: At age 16, 400 girls (100 from each testosterone quartile: 50 with oligo- or amenorrhoea and 50 with a normal menstrual cycle) were selected at random from the cohort for AMH measurement. Metabolic parameters were also assessed at age 16 in all participants. Postal questionnaires enquired about oligo- or amenorrhoea, hirsutism, contraceptive use and reproductive health at ages 16 and 26. Main results and role of chance: There was a significant correlation between AMH and testosterone at age 16 (r = 0.36, P < 0.001). AMH levels at age 16 were significantly higher among girls with oligo- or amenorrhoea compared with girls with normal menstrual cycles (35.9 pmol/l [95% CI: 33.2;38.6] versus 27.7 pmol/l [95% CI: 25.0;30.4], P < 0.001). AMH at age 16 was higher in girls who developed hirsutism at age 26 compared with the non-hirsute group (31.4 pmol/l [95% CI 27.1;36.5] versus 25.8 pmol/l [95% CI 23.3;28.6], P = 0.036). AMH at age 16 was also higher in women with PCOS at age 26 compared with the non-PCOS subjects (38.1 pmol/l [95% CI 29.1;48.4] versus 30.2 pmol/l [95% CI 27.9;32.4], P = 0.044). The sensitivity and specificity of the AMH (cut-off 22.5 pmol/l) for predicting PCOS at age 26 was 85.7 and 37.5%, respectively. The addition of testosterone did not significantly improve the accuracy of the test. There was no significant correlation between AMH levels and metabolic indices at age 16. Implications, reasons for cauntion: AMH is related to oligo- or amenorrhoea in adolescence, but it is not a good marker for metabolic factors. The relatively low rate of participation in the questionnaire at age 26 may also have affected the results. AMH was measured in a subset of the whole cohort. AMH measurement is lacking international standardization and therefore the concentrations and cut-off points are method dependent. Wider implications for the findings: Using a high enough cut-off value of AMH to predict which adolescents are likely to develop PCOS in adulthood could help to manage the condition from an early age due to a good sensitivity. However, because of its low specificity, it is not an ideal diagnostic marker, and its routine use in clinical practice cannot, at present, be recommended

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy

Effects of hormonal contraception on systemic metabolism: cross-sectional and longitudinal evidence

BACKGROUND:Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood.METHODS:A comprehensive molecular profile (75 metabolic measures and 37 cytokines) was measured for up to 5841 women (age range 24-49 years) from three population-based cohorts. Women using combined oral contraceptive pills (COCPs) or progestin-only contraceptives (POCs) were compared with those who did not use hormonal contraception. Metabolomics profiles were reassessed for 869 women after 6 years to uncover the metabolic effects of starting, stopping and persistently using hormonal contraception.RESULTS:The comprehensive molecular profiling allowed multiple new findings on the metabolic associations with the use of COCPs. They were positively associated with lipoprotein subclasses, including all high-density lipoprotein (HDL) subclasses. The associations with fatty acids and amino acids were strong and variable in direction. COCP use was negatively associated with albumin and positively associated with creatinine and inflammatory markers, including glycoprotein acetyls and several growth factors and interleukins. Our findings also confirmed previous results e.g. for increased circulating triglycerides and HDL cholesterol. Starting COCPs caused similar metabolic changes to those observed cross-sectionally: the changes were maintained in consistent users and normalized in those who stopped using. In contrast, POCs were only weakly associated with metabolic and inflammatory markers. Results were consistent across all cohorts and for different COCP preparations and different types of POC delivery.CONCLUSIONS:Use of COCPs causes widespread metabolic and inflammatory effects. However, persistent use does not appear to accumulate the effects over time and the metabolic perturbations are reversed upon discontinuation. POCs have little effect on systemic metabolism and inflammation.</p