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OBJECTIVE: The diagnosis of polycystic ovary syndrome (PCOS) remains challenging with international guidelines prioritising accurate cut-offs for individual diagnostic features. These diagnostic cut-offs are currently based on arbitrary percentiles, often from poorly characterised cohorts, and are dependent on variable laboratory ranges defined by assay manufacturers, limiting diagnostic accuracy. Cluster analysis is the recommended approach for defining normative cut-offs within populations for clinical syndromes. Few PCOS adult studies have applied cluster analysis, with no studies in adolescents. We aimed to define normative cut-offs for individual PCOS diagnostic features in a community-based population of adolescents using cluster analysis. DESIGN: This analysis utilised data from the Menstruation in Teenagers Study, a subgroup of the Raine Study, which is a population based prospective cohort of 244 adolescents whose mean age at PCOS assessment was 15.2 years. METHODS: K-means cluster analysis and receiver operating characteristics curves were used to define normative cut-offs for modified Ferriman-Gallwey (mFG) score, free testosterone (free T), free androgen index (FAI), and menstrual cycle length. RESULTS: Normative cut-offs for mFG, free T, FAI, and menstrual cycle lengths were 1.0, 23.4â pmol/L, 3.6, and 29 days, respectively. These corresponded to the 65th, 71st, 70th, and 59th population percentiles, respectively. CONCLUSION: In this novel study, we define the normative diagnostic criteria cut-offs in this unselected adolescent population and show that these cut-offs correspond to lower percentiles than conventional cut-offs. These findings highlight the pertinent need to re-define PCOS diagnostic cut-offs in adolescents. Validation is required in larger, multi-ethnic, and well-characterised adolescent cohorts.
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Síndrome do Ovário Policístico , Adulto , Feminino , Adolescente , Humanos , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/epidemiologia , Estudos Prospectivos , Testosterona , Análise por ConglomeradosRESUMO
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting 8%-13% of reproductive-aged women. The aetiology of the syndrome is complex, with genetic susceptibility, androgen exposure in early life and adiposity related dysfunction leading to perturbance in hypothalamic-ovarian function. PCOS clinical features are heterogeneous, with manifestations arising even in early adolescence, developing into multisystem reproductive, metabolic and psychological manifestations in adulthood. In this review, we will discuss challenges in the diagnosis of PCOS and understanding of the natural history of PCOS.
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Síndrome do Ovário Policístico , Adiposidade , Adolescente , Adulto , Androgênios , Feminino , Predisposição Genética para Doença , Humanos , Obesidade/complicações , Síndrome do Ovário Policístico/metabolismoRESUMO
STUDY QUESTION: What is the natural history of reproductive, psychological and oncological features in women with polycystic ovary syndrome (PCOS) in comparison to those without PCOS across the life course? SUMMARY ANSWER: Existing longitudinal data on changes in reproductive, psychological and oncological features in PCOS are inadequate and conflicting, but the limited evidence suggests that total testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) levels decline more significantly in women with PCOS than in those without PCOS, and the risk of gestational diabetes is higher in pregnant women with PCOS compared to their counterparts without PCOS. WHAT IS KNOWN ALREADY: The progression of reproductive, psychological and oncological features in PCOS remains unclear, which limits prevention and early diagnosis strategies across the lifespan. Understanding the natural history of PCOS is one of the overarching priorities in PCOS research. STUDY DESIGN, SIZE, DURATION: This is a systematic review of longitudinal cohort studies with a narrative presentation of findings. Databases MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews were searched between 15 January 2020 and 11 February 2021 with no language restrictions. Only studies published from the year 1990 to February 2021 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: In line with current guidelines for the assessment and management of PCOS, we included studies where participants were females with PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) consensus criteria. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 21 longitudinal studies including 62 123 participants over four continents reported reproductive, psychological and/or oncological outcomes. Participants were females aged between 15 and 49 years at baseline, with follow-up periods ranging from 4 weeks to 32 years. Consistent evidence based on limited studies suggests that total T and DHEAS levels decline to a greater degree in women with PCOS compared to those without PCOS, and the risk gestational diabetes is higher in women with PCOS than in those without PCOS. Evidence reporting changes over time in the majority of the remaining outcomes was unclear due to conflicting and/or insufficient information. LIMITATIONS, REASONS FOR CAUTION: There was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches. WIDER IMPLICATIONS OF THE FINDINGS: Understanding the natural history of PCOS and changes in diagnostic, reproductive, psychological and oncological features of PCOS across the lifespan is still a challenge and the existing literature is both limited and conflicting. It is important that future long-term prospective longitudinal studies are conducted in unselected and well-characterized populations. STUDY FUNDING/COMPETING INTEREST(S): This specific study was not funded. S.K. is supported by scholarships from the Research Training Program of the Commonwealth of Australia and Monash University; H.J.T. is supported by an Australian National Health and Medical Research Council fellowship; and A.E.J. is supported by the Australian National Health and Medical Research Council's Centre for Research Excellence in Women's Health in Reproductive Life. R.A. was employed by the American Society for Reproductive Medicine and is a consultant to Spruce Biosciences and Fortress Biotech. The other authors have no conflicts of interest to declare. REGISTRATION NUMBER: Prospero registration number: CRD42020165546.
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Diabetes Gestacional , Síndrome do Ovário Policístico , Austrália/epidemiologia , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Síndrome do Ovário Policístico/diagnóstico , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVE: Women with polycystic ovary syndrome (PCOS) have a worsened metabolic profile but the progression of cardiometabolic features over time is unclear. Understanding this natural history is a key priority in PCOS research and vital for guiding the prevention and management of this common condition. We explored cardiometabolic changes that are observed in women with PCOS compared to those without PCOS across the life course. DESIGN, PATIENTS AND MEASUREMENTS: A systematic review of longitudinal cohort studies was conducted across MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews between 15 January 2020 and 11 February 2021. Eligible studies included participants with or without PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) criteria. We included studies that were published from the year 1990 to 2021 with data on cardiometabolic outcomes as per the PCOS core outcomes set. RESULTS: There were 31 longitudinal studies with 28,316 participants from four continents. At the start of follow up, participants were aged between 1 year and 49 years with a follow-up period ranging from 2 to 32 years. Changes in BMI and the risk of coronary heart disease were similar in adult women with and without PCOS. Women with PCOS had a higher risk of Type 2 diabetes than their non-PCOS counterparts. Evidence for the majority of all other outcomes was conflicting and with inadequate data. CONCLUSION: Understanding the natural history of PCOS and particularly changes in cardiometabolic features remains challenging. Existing literature is extensive but heterogeneous and inconsistent. Longitudinal studies in unselected populations are needed to provide high-quality data in this area.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Síndrome do Ovário Policístico , Adulto , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Síndrome do Ovário Policístico/metabolismoRESUMO
OBJECTIVE: Menstrual cycle regularity underpins the diagnosis of polycystic ovary syndrome (PCOS), which is linked to adverse cardio-metabolic profile. However, links between menstrual disorders and metabolic conditions are often under-appreciated and not considered when assessing cardio-metabolic risk in women. We aimed to assess the risk of diabetes and heart disease in women with irregular menstrual cycles and those whose cycles were regular. METHODS: This was a community based longitudinal cohort study. We utilized the 1946 to 1951 birth cohort database (N = 13,714) of the Australian Longitudinal Study on Women's Health (ALSWH) over a 20-year follow-up period. Data were analysed using Cox regression models. RESULTS: Women with irregular menstrual cycles had 20% higher risk of developing heart disease [adjusted hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.01-1.43) compared with those with regular menstrual cycles. We also observed 17% higher risk of diabetes (HR: 1.17, 95% CI: 1.00-1.38) in women who had irregular menstrual cycles than in women who had regular menstrual cycles. The diabetes risk was 30% higher (HR: 1.30, 95% CI: 1.09-1.55) if women had irregular cycles and did not use hormone replacement therapy, but this was not significant on adjustment for all covariates. CONCLUSION: Having irregular menstrual cycles appears to be an early indicator for heart disease and diabetes. These findings suggest that irregular cycles among women in their forties may be linked to adverse cardio-metabolic outcomes. These women may benefit from screening and prevention strategies as recommended by related guidelines such as the international evidence-based guideline for the assessment and management of PCOS.
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Diabetes Mellitus , Cardiopatias , Síndrome do Ovário Policístico , Austrália/epidemiologia , Estudos de Coortes , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Ciclo Menstrual , Distúrbios Menstruais/epidemiologia , Síndrome do Ovário Policístico/complicaçõesRESUMO
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that is associated with negative metabolic, reproductive, endocrine, and psychological consequences among women of reproductive age. The diagnosis of PCOS remains challenging due to limited and conflicting evidence regarding definitions for each of the diagnostic features. This review of the recommended PCOS assessment criteria from the international evidence-based guideline highlights the crucial need to reassess, redefine, and optimize the diagnosis of PCOS. Notably, normal values and cut-offs need to be defined for each diagnostic feature across the lifespan and diverse ethnic groups. Understanding how these features cluster together and relate to short- and long-term health outcomes in PCOS is also vital. Ultimately, greater knowledge of the natural history of PCOS is needed through well-characterized, community-based longitudinal studies, which will inform future PCOS diagnosis guidelines and optimize women's health in reproductive life.
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Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/terapia , Reprodução , Saúde da MulherRESUMO
BACKGROUND: Blood smear microscopy remains the gold-standard method to diagnose and quantify malaria parasite density. In addition, parasite genotyping of select loci is the most utilized method for distinguishing recrudescent and new infections and to determine the number of strains per sample. In research settings, blood may be obtained from capillary or venous compartments, and results from these matrices have been used interchangeably. Our aim was to compare quantitative results for parasite density and strain complexity from both compartments. METHODS: In a prospective observational study, children and adults presenting with uncomplicated Plasmodium falciparum malaria, simultaneous capillary and venous blood smears and dried blood spots were collected over 42-days following treatment with artemether-lumefantrine. Blood smears were read by two microscopists, any discrepancies resolved by a third reader. Parasite DNA fingerprinting was conducted using six microsatellites. Bland Altman analysis and paired t-test/McNemar's test were used to assess the difference in density readings and measurements. RESULTS: Two hundred twenty-three participants were included in the analysis (177 children (35 HIV-infected/142 HIV-uninfected), 21 HIV-uninfected pregnant women, and 25 HIV-uninfected non-pregnant adults). Parasite density measurements did not statistically differ between capillary and venous blood smears at the time of presentation, nor over the course of 42-day follow-up. Characterization of merozoite surface protein-2 (MSP-2) genetic polymorphism demonstrated a higher level of strain diversity at the time of presentation in venous samples, as compared with capillary specimens (p = 0.02). There was a high degree of variability in genotype-corrected outcomes when pairs of samples from each compartment were compared using MSP-2 alone, although the variability was reduced with the use of multiple markers. CONCLUSIONS: Parasite density measurements do not statistically differ between capillary and venous compartments in all studied demographic groups at the time of presentation with malaria, or over the course of follow-up. More strains were detected by MSP-2 genotyping in venous samples than in capillary samples at the time of malaria diagnosis. The use of multiple polymorphic markers reduces the impact of variability in strain detection on genotype-corrected outcomes. This study confirms that both capillary and venous compartments can be used for sampling with confidence in the clinical research setting. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under registration no. NCT01717885 .