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Open access

Xiying Zeng, Yinxiang Huang, Mulin Zhang, Yun Chen, Jiawen Ye, Yan Han, Danyan Ma, Xin Zheng, Xiaohong Yan, and Changqin Liu

Objective

Anti-Müllerian hormone (AMH) is recognized as the most important biomarker for ovarian reserve. In this cross-sectional study, we aimed to explore the potential association of AMH with central obesity or general obesity in women with polycystic ovary syndrome (PCOS).

Methods

In this cross-sectional study, 179 patients with PCOS were enrolled and underwent anthropometric measurements (BMI and waist circumference (WC)) and serum AMH level detection. Pearson’s correlation and multivariable logistic regression analyses were performed to determine the associations of AMH with central obesity and general obesity.

Results

Subjects with increasing BMI showed significantly lower values of AMH (median (interquartile range (IQR)) 8.95 (6.03–13.60) ng/mL in normal weight group, 6.57 (4.18–8.77) ng/mL in overweight group, and 6.03 (4.34–9.44) ng/mL in obesity group, P = 0.001), but higher levels of systolic blood pressure, fasting insulin, total cholesterol, triglycerides, LDL-c, obesity indices (WC, hip circumferences, waist-to-hip ratio, waist-to-height ratio (WHtR), and Chinese visceral adiposity index (CVAI)). Compared with the group of PCOS women without central obesity, the group with central obesity had significantly lower value of AMH (median (IQR) 8.56 (5.29–12.96) ng/mL vs 6.22 (4.33–8.82) ng/mL; P = 0.003). Pearson’s correlation analysis showed that AMH was significantly and negatively correlated with BMI (r = −0.280; P < 0.001), WC (r = −0.263; P < 0.001), WHtR (r = −0.273; P < 0.001), and CVAI (r = −0.211; P = 0.006). Multivariate logistic regression analysis with adjustment for potential confounding factors showed that AMH was independently and negatively associated with central obesity but was not significantly associated with general obesity.

Conclusions

AMH was independently and negatively associated with central obesity. Closely monitoring the WC and AMH should be addressed in terms of assessing ovarian reserve in women with PCOS.

Open access

Sanna Mustaniemi, Marja Vääräsmäki, Johan G Eriksson, Mika Gissler, Hannele Laivuori, Hilkka Ijäs, Aini Bloigu, Eero Kajantie, and Laure Morin-Papunen

Objective

To study the roles of self-reported symptoms and/or prior diagnosis of polycystic ovary syndrome (PCOS) and other potential risk factors for gestational diabetes mellitus (GDM) and to clarify whether the screening of GDM in early pregnancy is beneficial for all women with PCOS.

Design

The FinnGeDi multicentre case-control study including 1146 women with singleton pregnancies diagnosed with GDM and 1066 non-diabetic pregnant women. There were 174 women with PCOS (symptoms and/or diagnosis self-reported by a questionnaire) and 1767 women without PCOS (data missing for 271).

Methods

The study population (N = 1941) was divided into four subgroups: GDM + PCOS (N = 105), GDM + non-PCOS (N = 909), non-GDM + PCOS (N = 69), and controls (N = 858). The participants’ characteristics and their parents’ medical histories were compared.

Results

The prevalence of PCOS was 10.4% among GDM women and 7.4% among non-diabetics (odds ratios (OR) 1.44, 95% CI: 1.05–1.97), but PCOS was not an independent risk for GDM after adjustments for participants’ age and pre-pregnancy BMI (OR 1.07, 95% CI: 0.74–1.54). In a multivariate logistic regression analysis, the most significant parameters associated with GDM were overweight, obesity, age ≥35 years, participant’s mother’s history of GDM, either parent’s history of type 2 diabetes (T2D) and participant’s own preterm birth.

Conclusions

The increased risk of GDM in women with PCOS was related to obesity and increased maternal age rather than to PCOS itself, suggesting that routine early screening of GDM in PCOS women without other risk factors should be reconsidered. Instead, family history of GDM/T2D and own preterm birth were independent risk factors for GDM.

Open access

Stavroula A Paschou, Eleni Palioura, Dimitrios Ioannidis, Panagiotis Anagnostis, Argyro Panagiotakou, Vasiliki Loi, Georgios Karageorgos, Dimitrios G Goulis, and Andromachi Vryonidou

Objective

The aim of this study was to investigate the impact of adrenal hyperandrogenism on insulin resistance and lipid profile in women with polycystic ovary syndrome (PCOS).

Patients and methods

We studied 372 women with PCOS according to the NIH criteria. 232 age- and BMI-matched women served as controls in order to define adrenal hyperandrogenism (DHEA-S >95th percentile). Then, patients with PCOS were classified into two groups: with adrenal hyperandrogenism (PCOS-AH, n = 108) and without adrenal hyperandrogenism (PCOS-NAH, n = 264). Anthropometric measurements were recorded. Fasting plasma glucose, insulin, lipid profile, sex hormone-binding globulin (SHBG) and androgen (TT, Δ4A, DHEA-S) concentrations were assessed. Free androgen index (FAI) and homeostatic model assessment-insulin resistance (HOMA-IR) index were calculated.

Results

Women with PCOS-AH were younger than PCOS-NAH (P < 0.001), but did not differ in the degree and type of obesity. No differences were found in HOMA-IR, total cholesterol, HDL-c, LDL-c and triglyceride concentrations (in all comparisons, P > 0.05). These metabolic parameters did not differ between the two groups even after correction for age. Women with PCOS-AH had lower SHBG (29.2 ± 13.8 vs 32.4 ± 11.8 nmol/L, P = 0.025) and higher TT (1.0 ± 0.2 vs 0.8 ± 0.4 ng/mL, P = 0.05) and Δ4A (3.9 ± 1.2 vs 3.4 ± 1.0 ng/mL, P = 0.007) concentrations, as well as FAI (14.1 ± 8.0 vs 10.2 ± 5.0, P < 0.001). These results were confirmed by a multiple regression analysis model in which adrenal hyperandrogenism was negatively associated with age (P < 0.001) and SHBG concentrations (P = 0.02), but not with any metabolic parameter.

Conclusions

Women with PCOS and adrenal hyperandrogenism do not exhibit any deterioration in insulin resistance and lipid profile despite the higher degree of total androgens.

Open access

Mírian Romitti, Vitor C Fabris, Patricia K Ziegelmann, Ana Luiza Maia, and Poli Mara Spritzer

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder affecting women of reproductive age. PCOS has been associated with distinct metabolic and cardiovascular diseases and with autoimmune conditions, predominantly autoimmune thyroid disease (AITD). AITD has been reported in 18–40% of PCOS women, depending on PCOS diagnostic criteria and ethnicity. The aim of this systematic review and meta-analysis was to summarize the available evidence regarding the likelihood of women with PCOS also having AITD in comparison to a reference group of non-PCOS women. We systematically searched EMBASE and MEDLINE for non-interventional case control, cross-sectional or cohort studies published until August 2017. The Ottawa–Newcastle Scale was used to assess the methodological quality of studies. Statistical meta-analysis was performed with R. Thirteen studies were selected for the present analysis, including 1210 women diagnosed with PCOS and 987 healthy controls. AITD was observed in 26.03 and 9.72% of PCOS and control groups respectively. A significant association was detected between PCOS and chance of AITD (OR = 3.27, 95% CI 2.32–4.63). Notably, after geographical stratification, the higher risk of AITD in PCOS women persisted for Asians (OR = 4.56, 95% CI 2.47–8.43), Europeans (OR = 3.27, 95% CI 2.07–5.15) and South Americans (OR = 1.86, 95% CI 1.05–3.29). AIDT is a frequent condition in PCOS patients and might affect thyroid function. Thus, screening for thyroid function and thyroid-specific autoantibodies should be considered in patients with PCOS even in the absence of overt symptoms. This systematic review and meta-analysis is registered in PROSPERO under number CRD42017079676.

Open access

Xia Wu, Zhiling Li, Wenjiang Sun, and Huan Zheng

Polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease in women. Hyperhomocysteinemia (H-Hcy) is closely related to arterial stiffness (AS) in patients with cardiovascular disease. This study aimed to investigate the relationship between serum homocysteine(Hcy) level and brachial-ankle pulse wave velocity (baPWV) in Chinese women with PCOS. A total of 124 PCOS women were enrolled and divided into two groups according to their baPWV values: normal, baPWV < 1400 cm/s and high AS, baPWV ≥ 1400 cm/s. Univariate analysis was performed to investigate the relative factors for baPWV, and multiple regression analysis was used to evaluate the association of Hcy with baPWV. The group with high AS (n = 35) had higher Hcy levels than the other group (n = 89; P < 0.05). Moreover, univariate analysis revealed that serum Hcy was positively correlated with baPWV (r = 0.133, P < 0.01). In multiple regression analysis, the age-adjusted serum Hcy level was positively correlated with baPWV (β = 0.201, P < 0.01). It remained positively associated with baPWV (β = 0.145, P < 0.01) after further adjustments for age, BMI, PCOS duration, systolic blood pressure, and homeostasis model assessment-insulin resistance as well as several other factors correlated with baPWV. Our results demonstrated that H-Hcy was significantly and independently related to elevated baPWV, suggesting that Hcy might play a role in the pathologic process of AS in women with PCOS. Further researches with more subjects are needed to explore whether Hcy would be a promising biomarker for the stratification management of PCOS women.

Open access

Lina S Silva-Bermudez, Freddy J K Toloza, Maria C Perez-Matos, Russell J de Souza, Laura Banfield, Andrea Vargas-Villanueva, and Carlos O Mendivil

Objective

To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis.

Patients and methods

Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, BMI, insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random-effects model. We performed subgroup analyses by study duration (<12 months vs ≥12 months) and polycystic ovary syndrome (PCOS) status.

Results

Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (P < 0.001) to 35.1 mg/dL for chlormadinone (P < 0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, P < 0.001) and drospirenone (+7.4 mg/dL, P < 0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (P < 0.001). Levonorgestrel (+6.8 mg/dL, P < 0.001) and norgestimate (+11.5 mg/dL, P = 0.003) increased LDLc, while dienogest decreased it (–7.7 mg/dL, P = 0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration.

Conclusion

Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.

Open access

Thozhukat Sathyapalan, Anne-Marie Coady, Eric S Kilpatrick, and Stephen L Atkin

Background

There is an increased risk of developing T2DM in women with polycystic ovary syndrome (PCOS), and there is evidence that statins improve metabolic parameters in these patients. However, there are some data to show that statins increase the risk of incipient diabetes.

Materials and methods

We have previously shown that 12 weeks of atorvastatin improves insulin resistance when measured using HOMA-IR. This post hoc analysis was designed to look at the effect of atorvastatin on pancreatic β cell function using HOMA-β in the same study. In this randomised, double-blind placebo controlled study, 40 medication-naïve patients with PCOS were randomised to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo.

Results

There was a significant reduction in HOMA-β (240 ± 3.2 vs 177 ± 2.3; P value <0.01) after 12 weeks of atorvastatin treatment, which was maintained by metformin in the subsequent 12 weeks. There were no changes in HOMA-β after the placebo or after subsequent metformin treatment.

There was no linear correlation between reduction in HOMA-β with improvement of free androgen index (FAI) (r 2 = 0.02; P = 0.72), testosterone (r 2 = 0.13; P = 0.49), SHBG (r 2 = 0.22; P = 0.48), hsCRP (r 2 = 0.19; P = 0.64), triglycerides (r 2 = 0.09; P = 0.12), total cholesterol (r 2 = 0.11; P = 0.32) or LDL-C (r 2 = 0.19; P = 0.38).

Conclusion

Treatment with atorvastatin for 12 weeks in women with PCOS significantly reduced HOMA-β. This could be potentially due to fall in β-cell requirement with improvement of insulin resistance rather than a reduction of β-cell function.

Open access

Krzysztof C Lewandowski, Justyna Płusajska, Wojciech Horzelski, Ewa Bieniek, and Andrzej Lewiński

Background

Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable.

Subjects and methods

In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices).

Results

There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = −0.999, HOMA-IR/McAuley index, r = −0.849 and between all OGTT-derived IR indices (e.g. r = −0.876, for IRI/Matsuda, r = −0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P < 0.001 for all), contrasting with a significant (P < 0.001), but highly variable correlation between IR indices derived from fasting vs OGTT-derived variables, ranging from r = −0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = −0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations.

Conclusions

Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution.

Open access

Raymond J Rodgers, Jodie C Avery, Vivienne M Moore, Michael J Davies, Ricardo Azziz, Elisabet Stener-Victorin, Lisa J Moran, Sarah A Robertson, Nigel K Stepto, Robert J Norman, and Helena J Teede

Objective

Many complex diseases exhibit co-morbidities often requiring management by more than one health specialist. We examined cross-speciality issues that ultimately affect the health and wellbeing of patients with polycystic ovary syndrome (PCOS). PCOS was originally described as a reproductive condition but is now recognised to also be a metabolic and psychological condition affecting 8–13% of women of reproductive age. With a four-fold increased risk of type 2 diabetes (DM2), the Population Attributable Risk of DM2 that could be avoided if PCOS were eliminated is a substantial 19–28% of women of reproductive age. To determine the extent to which PCOS is an important consideration in diabetes development, we examined publications, funding, guidelines and predictors of risk of developing DM2.

Results

We found that the topic of PCOS appeared in specialist diabetes journals at only 10% the rate seen in endocrinology journals – about 1 in 500 articles. We found research funding to be substantially less than for diabetes and found that diabetes guidelines and predictive tools for DM2 risk mostly ignore PCOS. This is surprising since insulin resistance in women with PCOS has a different aetiology and additionally women with PCOS are at increased risk of becoming overweight or obese – high risk factors for DM2.

Conclusions

We consider the causes of these concerning anomalies and discuss current activities to address the co-morbidities of PCOS, including the recent development of international guidelines, an international PCOS awareness program and potentially changing the name of PCOS to better reflect its metabolic consequences.

Open access

Signe Frøssing, Malin Nylander, Caroline Kistorp, Sven O Skouby, and Jens Faber

Context

Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP.

Objective

To investigate if treatment with liraglutide in women with PCOS reduces levels of the cardiovascular biomarkers MR-proADM, MR-proANP and copeptin.

Methods

Seventy-two overweight women with PCOS were treated with 1.8 mg/day liraglutide or placebo for 26 weeks in a placebo-controlled RCT. Biomarkers, anthropometrics, insulin resistance, body composition (DXA) and visceral fat (MRI) were examined.

Results

Baseline median (IQR) levels were as follows: MR-proADM 0.52 (0.45–0.56) nmol/L, MR-proANP 44.8 (34.6–56.7) pmol/L and copeptin 4.95 (3.50–6.50) pmol/L. Mean percentage differences (95% CI) between liraglutide and placebo group after treatment were as follows: MR-proADM −6% (−11 to 2, P = 0.058), MR-proANP −25% (−37 to −11, P = 0.001) and copeptin +4% (−13 to 25, P = 0.64). Reduction in MR-proANP concentration correlated with both increased heart rate and diastolic blood pressure in the liraglutide group. Multiple regression analyses with adjustment for BMI, free testosterone, insulin resistance, visceral fat, heart rate and eGFR showed reductions in MR-proANP to be independently correlated with an increase in the heart rate.

Conclusion

In an RCT, liraglutide treatment in women with PCOS reduced levels of the cardiovascular risk biomarkers MR-proANP with 25% and MR-proADM with 6% (borderline significance) compared with placebo. The decrease in MR-proANP was independently associated with an increase in the heart rate.