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

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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

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A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone-Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation

WOS:000306840400020Peer reviewe

Insulin resistance in polycystic ovary syndrome

Abstract The polycystic ovary syndrome, described first as the association of bilateral polycystic ovaries and amenorrhoea, oligomenorrhoea, hirsutism and obesity, was later shown to be a complex metabolic syndrome. The first purpose of this study was to investigate the occurrence of hyperinsulinaemia and the severity of insulin resistance and glucose tolerance disorders in polycystic ovary syndrome by means of the oral glucose tolerance test and the euglycaemic hyperinsulinaemic clamp. The next goal was to investigate whether women with polycystic ovary syndrome would benefit from insulin-sensitising drugs, and in particular to compare the effects of metformin and a contraceptive pill containing ethinyl oestradiol and cyproterone acetate. Altogether, 81 women with polycystic ovary syndrome and 34 healthy control subjects were involved in the study. Marked impairment of insulin sensitivity in obese subjects with polycystic ovary syndrome, including a decrease of both cellular oxidative and non-oxidative utilisation of glucose, and a slight non-significant decrease of insulin sensitivity in non-obese subjects was observed. Both non-obese and obese subjects with polycystic ovary syndrome exhibited increased abdominal obesity compared with the controls, confirming the fact that obesity, in particular abdominal obesity, is an important contributor in the development of insulin resistance in this syndrome. Metformin alleviated hyperandrogenism by essentially decreasing ovarian, but not adrenal androgen secretion. The improvement of hyperandrogenism and ovarian function seemed to be mediated by the improvement of hyperinsulinaemia, which resulted itself from subtle improvements in both hepatic insulin extraction and insulin sensitivity. Metformin decreased abdominal obesity and the release of free fatty acids from adipose tissue, and improved ovarian cyclicity and fertility. The transient decrease in serum leptin levels observed may have some role in the improvement of ovarian function. The contraceptive pill significantly improved hyperandrogenism and hirsutism, and it slightly affected glucose metabolism. Thus, it could be the treatment of choice in women with hirsutism problems and no fertility hopes. Metformin could be the drug of choice for women with polycystic ovary syndrome who wish to conceive. Because of its beneficial metabolic effects, the value of metformin in reducing the risk of cardiovascular diseases in polycystic ovary syndrome needs to be further studied

Aging women with polycystic ovary syndrome:menstrual cycles, metabolic health, and health-related quality of life

Abstract Women with polycystic ovary syndrome (PCOS) in their reproductive years present with metabolic dysfunction and thus increased likelihood of long-term health consequences and diminished well-being in later life. Owing to their larger ovarian reserve, however, they may experience menopause at later age and protection from metabolic and cardiovascular diseases. Moreover, previous studies have indicated that late reproductive-aged, normal-weight women with PCOS do not seem to have the expected high risk for type 2 diabetes (T2D), as previously thought. Health-related quality of life, nevertheless, is decreased in women with PCOS up until late fertile age, warranting attention and actions from the health care personnel. Given conflicting reports regarding the risk of cardiovascular diseases, future research with well characterized and adequately sized PCOS populations are needed, as well as studies aiming to improve their health-related quality of life

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

Peer reviewe

Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome : a regional cross-sectional study

BACKGROUND: Polycystic ovary syndrome is a heterogeneous disorder and its presentation varies with race and ethnicity. Reproductive-age women with polycystic ovary syndrome are at increased risk of metabolic syndrome; however, it is not clear if prevalence of metabolic syndrome and clustering of its components differs based on race and ethnicity. Moreover, the majority of these women do not undergo routine screening for metabolic syndrome. OBJECTIVE: We sought to compare the prevalence of metabolic syndrome and clustering of its components in women with polycystic ovary syndrome in the United States with women in India, Brazil, Finland, and Norway. STUDY DESIGN: This is a cross-sectional study performed in 1089 women with polycystic ovary syndrome from 1999 through 2016 in 5 outpatient clinics in the United States, India, Brazil, Finland, and Norway. Polycystic ovary syndrome was defined by the Rotterdam criteria. Main outcome measures were: metabolic syndrome prevalence, blood pressure, body mass index, fasting high-density lipoprotein cholesterol, fasting triglycerides, and fasting glucose. Data from all sites were reevaluated for appropriate application of diagnostic criteria for polycystic ovary syndrome, identification of polycystic ovary syndrome phenotype, and complete metabolic workup. The US White women with polycystic ovary syndrome were used as the referent group. Logistic regression models were used to evaluate associations between race and metabolic syndrome prevalence and its components and to adjust for potential confounders, including age and body mass index. RESULTS: The median age of the entire cohort was 28 years. Women from India had the highest mean Ferriman-Gallwey score for clinical hyperandrogenism (15.6 +/- 6.5, P <.001). The age-adjusted odds ratio for metabolic syndrome was highest in US Black women at 4.52 (95% confidence interval, 2.46-8.35) compared with US White women. When adjusted for age and body mass index, the prevalence was similar in the 2 groups. Significantly more Black women met body mass index and blood pressure criteria (P <.001), and fewer met fasting triglycerides criteria (P <.05). The age- and body mass index-adjusted prevalence of metabolic syndrome was highest in Indian women (odds ratio, 6.53; 95% confidence interval, 3.47-12.30) with abnormalities in glucose and fasting high-density lipoprotein cholesterol criterion and in Norwegian women (odds ratio, 2.16; 95% confidence interval, 1.17-3.98) with abnormalities in blood pressure, glucose, and fasting high-density lipoprotein cholesterol criterion. The Brazilian and Finnish cohorts had similar prevalence of metabolic syndrome and its components compared to US White women. CONCLUSION: Despite a unifying diagnosis of polycystic ovary syndrome, there are significant differences in the prevalence of metabolic syndrome and clustering of its components based on race and ethnicity, which may reflect contributions from both racial and environmental factors. Our findings indicate the prevalence of metabolic syndrome components varies in women with polycystic ovary syndrome, such that compared to White women from the United States, Black US women had the highest prevalence, whereas women from India and Norway had a higher prevalence of metabolic syndrome independent of obesity. The differences in clustering of components of metabolic syndrome based on ethnicity highlight the need to routinely perform complete metabolic screening to identify specific targets for cardiovascular risk reduction strategies in these reproductive-age women.Peer reviewe

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

Abstract 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. Desing: 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 = 0.010) and women with Rotterdam-PCOS (P = 0.019), 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

Obesity represses CYP2R1, the vitamin D 25‐hydroxylase, in the liver and extrahepatic tissues

Abstract Low plasma level of 25‐hydroxyvitamin D (25‐OH‐D), namely vitamin D deficiency, is associated with obesity and weight loss improves 25‐OH‐D status. However, the mechanism behind obesity‐induced vitamin D deficiency remains unclear. Here, we report that obesity suppresses the expression of cytochrome P450 (CYP) 2R1, the main vitamin D 25‐hydroxylase, in both mice and humans. In humans, weight loss induced by gastric bypass surgery increased the expression of CYP2R1 in the s.c. adipose tissue suggesting recovery after the obesity‐induced suppression. At the same time, CYP27B1, the vitamin D 1α‐hydroxylase, was repressed by the weight loss. In a mouse (C57BL/6N) model of diet‐induced obesity, the plasma 25‐OH‐D was decreased. In accordance, the CYP2R1 expression was strongly repressed in the liver. Moreover, obesity repressed the expression of CYP2R1 in several extrahepatic tissues, the kidney, brown adipose tissue, and testis, but not in the white adipose tissue. Obesity had a similar effect in both male and female mice. In mice, obesity repressed expression of the vitamin D receptor in brown adipose tissue. Obesity also upregulated the expression of the vitamin D receptor and CYP24A1 in the s.c. adipose tissue of a subset of mice; however, no effect was observed in the human s.c. adipose tissue. In summary, we show that obesity affects CYP2R1 expression both in the mouse and human tissues. We suggest that in mouse the CYP2R1 repression in the liver plays an important role in obesity‐induced vitamin D deficiency. Currently, it is unclear whether the CYP2R1 downregulation in extrahepatic tissues could contribute to the obesity‐induced low plasma 25‐OH‐D, however, this phenomenon may affect at least the local 25‐OH‐D concentrations