Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome

Context/Objective: Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women. Patients/Design: A total of 137 consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of diagnostic and metabolic features. Insulin sensitivity was measured by the glucose clamp technique. Results: Among women with PCOS, 84.7% had hyperandrogenism, 84.7% had chronic oligoanovulation, and 89% had polycystic ovaries. According to the individual combinations of these features, 69.4% of women had the classic phenotype, 15.3% had the ovulatory phenotype, and 15.3% had the normoandrogenic phenotype. Most subjects (71.4%) were insulin resistant. However, insulin resistance frequency differed among phenotypes, being 80.4%, 65.0%, and 38.1%, respectively, in the 3 subgroups (P < .001). Although none of the PCOS diagnostic features per se was associated with the impairment in insulin action, after adjustment for covariates, the classic phenotype and, to a lesser extent, the ovulatory phenotype were independently associated with insulin resistance, whereas the normoandrogenic phenotype was not. Metabolic syndrome frequency was also different among phenotypes (P = .030). Conclusions: There is a scale of metabolic risk among women with PCOS. Although no single diagnostic features of PCOS are independently associated with insulin resistance, their combinations, which define PCOS phenotypes, may allow physicians to establish which women should undergo metabolic screening. In metabolic terms, women belonging to the normoandrogenic phenotype behave as a separate group

Quasi-equilibrium states in thermotropic liquid crystals studied by multiple quantum NMR

Previous work showed that by means of the Jeener-Broekaert JB experiment, two quasiequilibrium states can be selectively prepared in the proton spin system of thermotropic nematic liquid crystals LCs in a strong magnetic field. The similarity of the experimental results obtained in a variety of LC in a broad Larmor frequency range, with crystal hydrates, supports the assumption that also in LC the two spin reservoirs, into which the Zeeman order is transferred, originate in the dipolar energy and that they are associated with a separation in energy scales: A constant of motion related to the stronger dipolar interactions S, and a second one W corresponding to the secular part of the weaker dipolar interactions with regard to the Zeeman and the strong dipolar part. We study the nature of these quasi-invariants in nematic 5CB 4-pentyl-4-biphenyl-carbonitrile and measure their relaxation times by encoding the multiple-quantum coherences of the states following the JB pulse pair on two orthogonal bases, Z and X. The experiments were also performed in powder adamantane at 301 K which is used as a reference compound having only one dipolar quasi-invariant. We show that the evolution of the quantum states during the buildup of the quasiequilibrium state in 5CB prepared under the S condition is similar to the case of powder adamantane and that their quasiequilibrium density operators have the same tensor structure. In contrast, the second constant of motion, whose explicit operator form is not known, involves a richer composition of multiple-quantum coherences of even order on the X basis, in consistency with the truncation inherent in its definition. We exploited the exclusive presence of coherences of 4,6,8, besides 0 and 2 under the W condition to measure the spin-lattice relaxation time TW accurately, so avoiding experimental difficulties that usually impair dipolar order relaxation measurement such as Zeeman contamination at high fields and also superposition of the different quasi-invariants. This procedure opens the possibility of measuring the spin-lattice relaxation of a quasi-invariant independent of the Zeeman and S reservoirs, so incorporating a new relaxation parameter useful for studying the complex molecular dynamics in mesophases. In fact, we report the first measurement of TW in a LC at high magnetic fields. Comparison of the obtained value with the one corresponding to a lower field 16 MHz points out that the relaxation of the W-order strongly depends on the intensity of the external magnetic field, similarly to the case of the S reservoir, indicating that the relaxation of the W-quasi-invariant is also governed by the cooperative molecular motions.Fil: Buljubasich Gentiletti, Lisandro. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomia y Física. Sección Física. Grupo de Resonancia Magnética Nuclear; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monti, Gustavo Alberto. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomia y Física. Sección Física. Grupo de Resonancia Magnética Nuclear; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Acosta, Rodolfo Héctor. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomia y Física. Sección Física. Grupo de Resonancia Magnética Nuclear; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bonin, Claudio Julio. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: González, Cecilia Élida. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zamar, Ricardo César. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomia y Física. Sección Física. Grupo de Resonancia Magnética Nuclear; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Metabolic inflexibility is a feature of women with polycystic ovary syndrome and is associated with both insulin resistance and hyperandrogenism

Context: Metabolic inflexibility, ie, the impaired ability of the body to switch from fat to carbohydrate oxidation under insulin-stimulated conditions, is associated with insulin resistance. This alteration in metabolic plasticity can lead to organ dysfunction and is considered a key issue among the abnormalities of the metabolic syndrome. It is still unknown whether this phenomenon occurs in women with polycystic ovary syndrome (PCOS). Objective: Our objective was to examine whether metabolic inflexibility is a feature of PCOS women and whether hyperandrogenism may contribute to this phenomenon. Design and Patients: Eighty-nine Caucasian women with PCOS were submitted to hyperinsulinemic-euglycemic clamp. Respiratory exchange ratios were evaluated at baseline and during hyperinsulinemia by indirect calorimetry to quantify substrate oxidative metabolism. Total testosterone was measured by liquid chromatography mass spectrometry and free testosterone by equilibrium dialysis. Setting: Outpatients were seen in a tertiary care academic center. Main Outcome Measure: Metabolic flexibility was assessed by the change in respiratory quotient upon insulin stimulation. Results: Sixty-five of the 89 PCOS women(73%) had increased serum free testosterone, 68 (76%) were insulin resistant, and 62 (70%) had an impaired metabolic flexibility. Comparison of hyperandrogenemic and normoandrogenemic women showed that the 2 subgroups were of similar age but differed in terms of several anthropometric and metabolic features. In particular, hyperandrogenemic women had greater body mass index (32.9 +/- 1.0 vs 24.7 +/- 0.9 kg/m(2), P < .001) and lower glucose utilization during the clamp (9.2 +/- 0.4 vs 10.9 +/- 0.7 mg/kg fat-free mass . min, P < .023) and metabolic flexibility (0.09 +/- 0.06 vs 0.12 +/- 0.01, P < .014). In univariate analysis, metabolic flexibility was associated with several anthropometric, endocrine, and metabolic features. In multivariate analysis, this feature was directly associated with baseline respiratory quotient and insulin sensitivity and inversely with free testosterone and free fatty acids concentrations under insulin suppression (R-2 = 0.634, P < .001). Conclusions: Metabolic inflexibility is a feature of PCOS women. Both insulin resistance and androgen excess might contribute to this abnormality

Are We Asking Too Much of the Health Sector? Exploring the Readiness of Brazilian Primary Healthcare to Respond to Domestic Violence Against Women

BACKGROUND: There is growing recognition of the health sector's potential role in addressing domestic violence (DV) against women. Although Brazil has a comprehensive policy framework on violence against women (VAW), implementation has been slow and incomplete in primary healthcare (PHC), and little is known about the implementation challenges. This paper aims to assess the readiness of two PHC clinics in urban Brazil to integrate an intervention to strengthen their DV response. METHODS: We conducted 20 semi-structured interviews with health managers and health providers; a document analysis of VAW and DV policies from São Paulo and Brazil; and 2 structured facility observations. Data were analysed using thematic analysis. RESULTS: Findings from our readiness assessment revealed gaps in both current policy and practice needing to be addressed, particularly with regards to governance and leadership, health service organisation and health workforce. DV received less political recognition, being perceived as a lower priority compared to other health issues. Lack of clear guidance from the central and municipal levels emerged as a crucial factor that weakened DV policy implementation both by providers and managers. Furthermore, responses to DV lost visibility, as they were diluted within generic violence responses. The organizational structure of the PHC system in São Paulo, which prioritised the number of consultations and household visits as the main performance indicators, was an additional difficulty in legitimising healthcare providers' time to address DV. Individual-level challenges reported by providers included lack of time and knowledge of how to respond, as well as fears of dealing with DV. CONCLUSION: Assessing readiness is critical because it helps to evaluate what services and infrastructure are already in place, also identifying obstacles that may hinder adaptation and integration of an intervention to strengthen the response to DV before implementation

An evidence-based primary health care intervention to address domestic violence against women in Brazil: a mixed method evaluation.

BACKGROUND: Health systems have a critical role in a multi-sectoral response to domestic violence against women (DVAW). However, the evidence on interventions is skewed towards high income countries, and evidence based interventions are not easily transferred to low-and middle-income countries (LMIC) where significant social, cultural and economic differences exist. We evaluated feasibility and acceptability of implementation of an intervention (HERA-Healthcare Responding to Violence and Abuse) to improve the response to DVAW in two primary health care clinics (PHC) in Brazil. METHODS: The study design is a mixed method process and outcome evaluation, based on training attendance records, semi-structured interviews (with 13 Primary Health Care (PHC) providers, two clinic directors and two women who disclosed domestic violence), and identification and referral data from the Brazilian Epidemiological Surveillance System (SINAN). RESULTS: HERA was feasible and acceptable to women and PHC providers, increased providers' readiness to identify DVAW and diversified referrals outside the health system. The training enhanced the confidence and skills of PHC providers to ask directly about violence and respond to women's disclosures using a women centred, gender and human rights perspective. PHC providers felt safe and supported when dealing with DVAW because HERA emphasised clear roles and collective action within the clinical team. A number of challenges affected implementation including: differential managerial support for the Núcleo de Prevenção da Violência (Violence Prevention Nucleus-NPV) relating to the allocation of resources, monitoring progress and giving feedback; a lack of higher level institutional endorsement prioritising DVAW work; staff turnover; a lack of feedback from external support services to PHC clinics regarding DVAW cases; and inconsistent practices regarding documentation of DVAW. CONCLUSION: Training should be accompanied by system-wide institutional change including active (as opposed to passive) management support, allocation of resources to support roles within the NPV, locally adapted protocols and guidelines, monitoring progress and feedback. Communication and coordination with external support services and documentation systems are crucial and need improvement. DVAW should be prioritised within leadership and governance structures, for example, by including DVAW work as a specific commissioning goal

ASSOCIATION BETWEEN PHENOTYPES AND METABOLIC ABNORMALITIES IN WOMEN WITH PCOS

Associazione fra fenotipi e anomalie metaboliche nelle donne con sindrome dell\u2019ovaio policistico Premesse. La sindrome dell'ovaio policistico (PCOS) \ue8 una patologia eterogenea. In base alle decisioni prese nella Consensus Conference tenutasi a Rotterdam nel 2003 (Fertil Steril 2004;81:19), la diagnosi di PCOS pu\uf2 essere oggi posta in presenza di diverse combinazioni di tre caratteristiche: iperandrogenismo clinico e/o biochimico, oligo-anovulazione cronica, aspetto micropolicistico delle ovaie. Tuttavia \ue8 ancora discusso se le donne diagnosticate come PCOS in base a queste diverse combinazioni rappresentino realmente diversi fenotipi della stessa patologia. Molte donne affette da PCOS mostrano anche insulinoresistenza e altre alterazioni metaboliche. Questi elementi al momento non hanno significato diagnostico ma sono aspetti considerati importanti per la salute di queste pazienti. Scopo. Scopo dello studio \ue8 stato valutare se l'insulinoresistenza e le anomalie metaboliche si associno in maniera simile ai diversi elementi utilizzati per la diagnosi di PCOS. Materiali e metodi. Nello studio sono state incluse 114 donne con PCOS, diagnosticata secondo i criteri di Rotterdam (et\ue0 media+DS 24.1+5.6 anni, BMI 30.1+8.6 kg/m2), e 35 controlli sani con peso normale. L'iperandrogenismo \ue8 stato valutato clinicamente e attraverso il dosaggio di testosterone totale e SHBG, utilizzando la formula di Vermeulen per il calcolo del testosterone libero (J Clin Endocrinol Metab 1999;84:3666). Nelle donne con pi\uf9 di 8 cicli mestruali/anno, per verificare la funzione ovulatoria \ue8 stato misurato il progesterone sierico in fase luteale. L'ecografia pelvica \ue8 stata eseguita quando possibile per via transvaginale, misurando il numero dei follicoli ovarici con i loro diametri e il volume di entrambi gli annessi. Inoltre, queste pazienti sono state anche sottoposte a clamp euglicemico iperinsulinemico, metodica gold standard per la valutazione della sensibilit\ue0 insulinica in vivo, a flussimetria Doppler delle arterie uterine, con misurazione degli indici di pulsatilit\ue0 e resistenza, a OGTT 75 g, per determinare la tolleranza glucidica, e alla misurazione dei livelli sierici dei lipidi e dell'acido urico. Risultati. Di queste donne con diagnosi di PCOS l'80% aveva iperandrogenismo, l'88% oligoanovulazione e il 90% una morfologia policistica dell\u2019ovaio. Sulla base dei valori di utilizzazione insulino-stimolata di glucosio durante il clamp il 65% delle pazienti presentava insulinoresistenza. Inoltre il 36% di loro aveva una sindrome metabolica, secondo i criteri IDF 2009 (Circulation 2009;20:1640). Le donne con PCOS presentavano numerose differenze antropometriche, metaboliche ed endocrine rispetto ai controlli. Confrontando gruppi di donne con BMI simile molte di queste differenze non erano pi\uf9 significative. Tuttavia, la glicemia a digiuno e la sensibilit\ue0 insulinica rimanevano statisticamente diverse nelle donne con PCOS e nei controlli. La sensibilit\ue0 insulinica era sensibilmente pi\uf9 bassa nelle donne con PCOS che avevano iperandrogenismo rispetto a quelle senza tale caratteristica. Analogamente, altre caratteristiche metaboliche erano diverse in questi due sottogruppi di donne con PCOS. Invece, l'oligoanovulazione e gli aspetti ecografici delle ovaie non si associavano con le caratteristiche metaboliche di questi soggetti. Includendo il BMI come covariata, l'associazione tra iperandrogenismo ed insulinoresistenza si attenuava ma non scompariva. L'indice di pulsatilit\ue0 e quello di resistenza delle arterie uterine erano entrambi significativamente pi\uf9 alti nelle donne con PCOS che nei controlli (p<0.001). Tali parametri correlavano con i livelli di SHBG e testosterone libero, ma non con le caratteristiche antropometriche e metaboliche di queste donne. Conclusioni. L'insulinoresistenza e la sindrome metabolica sono reperti frequenti nelle giovani donne con PCOS. L'eccesso di massa grassa si associa con l'iperandrogenismo e le anomalie metaboliche, ma non rende completamente conto della relazione tra iperandrogenismo e insulinoresistenza. Tra gli elementi attualmente utilizzati per la diagnosi di PCOS solo l'iperandrogenismo \ue8 associato con l'insulinoresistenza e altre anomalie metaboliche, mentre non lo sono l'oligoanovulazione e la morfologia policistica dell\u2019ovaio. Questi dati suggeriscono che le donne con PCOS normoandrogeniche possono avere una condizione clinica meno severa. Le donne con PCOS presentano anche alterazioni flussimetriche delle arterie uterine, che si associano all'iperandrogenismo ma non alle anomalie metaboliche e antropometriche.Association between phenotypes and metabolic abnormalities in women with polycystic ovary syndrome Background. Polycystic ovary syndrome (PCOS) is a heterogeneous disorder. According to the current Rotterdam criteria (Fertil Steril 2004;81:19) it may be diagnosed according to the presence of different combinations of three features, namely clinical and/or biochemical hyperandrogenism, chronic oligo-anovulation and ultrasonographic appearance of the ovaries. However, it is still under debate whether subjects diagnosed by these different combinations truly represent different phenotypes of the same condition. Many PCOS women show insulin resistance and other metabolic alterations, which are considered a relevant health issue in this condition. Aim. The aim of this study was to assess whether the different elements used in PCOS diagnosis similarly cluster with insulin resistance and metabolic abnormalities. Subjects and Methods. This study included 114 women with PCOS (mean age+SD 24.1+5.6 yr, BMI 30.1+8.6 kg/m2), diagnosed according to the Rotterdam criteria, and 35 normal-weight healthy controls. Hyperandrogenism was assessed by clinical examination and serum testosterone and SHBG assay, with calculation of free testosterone concentrations by the Vermeulen formula (J Clin Endocrinol Metab 1999;84:3666). In women with more than 8 menses per year, oligo-anovulation was assessed by luteal phase measurement of serum progesterone. Ovarian ultrasonography was carried out, when possible, with a transvaginal approach, recording the number of the follicles and their diameters, and the ovarian volume in both ovaries. In addition, insulin sensitivity was measured by the glucose clamp technique, uterine arteries pulsatility and resistance indices were measured by Doppler analysis, glucose tolerance was assessed by 75g OGTT. Serum lipids and uric acid were also measured. Results. Among these PCOS women, 80% had hyperandrogenism, 88% had oligo-anovulation and 90% had polycystic ovaries. Insulin induced glucose utilization in the clamp studies was reduced in 65% of subjects and the metabolic syndrome was diagnosed, according to the IDF 2009 criteria (Circulation 2009;20:1640), in 36% of them. A number of anthropometric, metabolic and endocrine features were different between PCOS women and controls. When BMI-matched groups were compared, many of these differences were no longer statistically significant. However, fasting glucose and insulin sensitivity, as well as the expected differences in serum androgens, remained statistically different between the groups. Insulin sensitivity was significantly lower in hyperandrogenic than in non-hyperandrogenic PCOS women. Similarly, other metabolic features were different between these two subgroups of patients. However, both oligo-anovulation and the ultrasonographic features of the ovaries were not associated with the metabolic features. Inclusion in the analysis of BMI, as a covariate, reduced but did not eliminate the association between hyperandrogenism and insulin resistance. At Doppler analysis, both the pulsatility index and the resistance index of the uterine arteries were significantly higher in PCOS women than in controls (both p<0.001) and these differences were maintained when BMI-matched subjects were compared. These features correlated with SHBG and free testosterone levels, whereas no relationships were found with the metabolic features. Conclusions. Insulin resistance and the metabolic syndrome are common findings in young PCOS women. Fat mass excess is associated with both hyperandrogenism and the metabolic abnormalities, but it does not entirely account for the relationship between androgen excess and insulin resistance. Among the elements currently used for diagnosing PCOS, only hyperandrogenism is associated with insulin resistance and the other metabolic abnormalities of these women, whereas oligo-anovulation and polycystic ovaries are not. These findings suggest that non-hyperandrogenic PCOS women may have a less severe clinical condition. PCOS is also characterized by Doppler flussimetric alterations of the uterine arteries, which are associated with hyperandrogenism, but not with the anthropometric and metabolic abnormalities

Polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common and heterogeneous disorder of young women, affecting at least 6-8% of subjects in the reproductive age. Diagnosis is based on the presence of variable combinations of at least two out of 3 clinical elements, i.e. hyperandrogenism (clinical and/or biochemical), chronic oligo-anovulation and polycystic ovarian morphology, after exclusion of secondary causes. PCOS is also frequently characterized by obesity and insulin resistance, with an associated risk of metabolic alterations and cardiovascular disease. The presence of both hyperandrogenism and oligo-anovulation identifies in these women the classic phenotype of this syndrome, which is characterized by a worse metabolic profile. Therefore, the detection of hyperandrogenism is of major clinical significance in PCOS subjects. Unfortunately, the assessment of both clinical and biochemical hyperandrogenism usually relies on inaccurate methods. The treatment of these women should be personalized: lifestyle intervention is always recommended in subjects with fat excess, whereas the choice of medications depends on specific needs and characteristics of each patient

Low body weight and menstrual dysfunction are common findings in both elite and amateur ballet dancers

Background. Several studies have reported that low body weight and menstrual alterations are very frequent findings in elite dancers, suggesting they could be at risk for associated medical problems. However, it is still largely unknown whether these alterations are also common in the very large number of young amateur dancers.Aim. The aim of this study was to assess whether there is an increased prevalence of menstrual dysfunction also in amateur dancers.Material/Subjects and Methods. 92 professional ballet dancers, 93 non-professional ballet dancers, and 293 (160 sedentary, 133 physically active) control women, ranging in age 14-23 yr were included in the study. In these subjects a detailed questionnaire that included questions on weight, height, age at menarche, training profile and menstrual alterations was administered.Results. BMI was lower in both professional and non-professional dancers than in controls. Frequency of menstrual dysfunction was 51%, 34% and 21% in professional dancers, non-professional dancers and controls, respectively (p<0.0001). Amenorrhea was reported by 23% of professional dancers, vs 1-7% in the other groups (p<0.0001). Age at menarche occurred later in professional dancers than in the other groups. Logistic regression analyses showed that menstrual dysfunction was associated with the training profile in professional dancers, and with BMI in non-professional dancers. Age at menarche was associated with menstrual dysfunction in both groups.Conclusions. This study shows that low body weight and menstrual dysfunction are frequent findings also in amateur ballet dancers

Defining probabilities of bowel resection in deep endometriosis of the rectum: Prediction with preoperative magnetic resonance imaging

AimDeep endometriosis of the rectum is a highly challenging disease, and a surgical approach is often needed to restore anatomy and function. Two kinds of surgeries may be performed: radical with segmental bowel resection or conservative without resection. Most patients undergo magnetic resonance imaging (MRI) before surgery, but there is currently no method to predict if conservative surgery is feasible or whether bowel resection is required. The aim of this study was to create an algorithm that could predict bowel resection using MRI images, that was easy to apply and could be useful in a clinical setting, in order to adequately discuss informed consent with the patient and plan the an appropriate and efficient surgical session.MethodsWe collected medical records from 2010 to 2016 and reviewed the MRI results of 52 patients to detect any parameters that could predict bowel resection. Parameters that were reproducible and with a significant correlation to radical surgery were investigated by statistical regression and combined in an algorithm to give the best prediction of resection.ResultsThe calculation of two parameters in MRI, impact angle and lesion size, and their use in a mathematical algorithm permit us to predict bowel resection with a positive predictive value of 87% and a negative predictive value of 83%.Conclusions MRI could be of value in predicting the need for bowel resection in deep endometriosis of the rectum. Further research is required to assess the possibility of a wider application of this algorithm outside our single-center study