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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.

To investigate lifetime reproductive outcomes and the relationship of ideal family size (IFS) achievement with metabolic, psychiatric and reproductive history in women with and without polycystic ovary syndrome (PCOS).Cross-sectional.A total of 9034 women with (n = 778) and without self-reported PCOS (n = 8256) born between 1973 and 1978 in the Australian Longitudinal Study on Women's Health.Self-reported IFS achievement and total number of live births.Women with and without PCOS aspired for similar IFS. Compared with women without PCOS, significantly less women with PCOS achieved their IFS (53.08% vs. 60.47%, p 0.001). Higher proportion of women with PCOS did not achieve a live birth (37.15% vs. 31.64%, p = 0.002) and their median total number of live births was also lower (1 vs. 2, p 0.001) than women without PCOS. After controlling for sociodemographic factors, negative associations were observed between IFS achievement and PCOS status, various metabolic, psychiatric and reproductive history. However, only hypertension (adjusted odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.67-1.00), obesity (adjusted OR: 0.79, 95% CI: 0.69-0.90), history of in vitro fertilisation use (IVF) (adjusted OR: 0.49, 95% CI: 0.38-0.63) and maternal age at first childbirth (adjusted OR: 0.92, 95% CI: 0.91-0.93) remained inversely associated with achievement of IFS in further multivariable regression models.Metabolic conditions and reproductive history of maternal age at first childbirth and history of IVF use, but not psychological conditions, were associated with reduced odds of achieving IFS. Early family planning/initiation and optimisation of metabolic health may help to improve reproductive outcomes.

Objectives A higher risk of hypertensive disorders in pregnancy (HDP) is frequently reported in women with polycystic ovary syndrome (PCOS). These women, however, have a higher risk profile for HDP compared with women without PCOS. The aim of this study was to elucidate the impact of PCOS per se on the incidence of HDP through post hoc subgroup analyses of the Australian Longitudinal Study on Women's Health by level of risk. Design Longitudinal study. Patients Of a total of 14,247 participants, 5838 women met the inclusion criteria. Eligible women were required to report PCOS and HDP status in at least one pregnancy within the study. Measurements Included risk factors were age, body mass index, country of birth, parity, multiple pregnancy, subfertility, infertility treatment (hormonal vs. in vitro fertilization), gestational diabetes (GDM), family history of GDM and socioeconomic status. Longitudinal association between PCOS and HDP was assessed the using Cox proportional hazard regression with Efron's method. Results While PCOS was associated with a higher incidence of HDP in a univariate model [hazard ratio (HR): 1.34, 95% confidence interval (CI): 1.05, 1.72], the significance was not retained after adjustment for risk factors [HR: 1.19, 95% CI: 0.79, 1.79]. However in multivariate analysis of subgroups, PCOS remained significantly associated with higher risk of HDP in non-obese women only [HR: 1.77, 95% CI: 1.11, 2.82]. Conclusions Higher risk of HDP in PCOS is likely related to risk factors other than PCOS.

BACKGROUND Type 1 diabetes (T1D) is associated with reproductive dysfunction, particularly in the setting of poor metabolic control. Improvements in contemporary management ameliorate these problems, albeit at the cost of increased exogenous insulin and rising obesity, with emerging reproductive implications. OBJECTIVE To evaluate changes in body mass index (BMI) and the relationship between obesity, menstrual irregularity and polycystic ovary syndrome (PCOS) in young women with T1D, compared with controls. METHODS Longitudinal observational study using data from the Australian Longitudinal Study in Women's Health of the cohort born in 1989-95, from 2013 to 2015. Three questionnaires administered at baseline and yearly intervals were used to evaluate self-reported menstrual irregularity, PCOS and BMI. RESULTS Overall, 15 926 women were included at baseline (T1D, n = 115; controls, n = 15 811). 61 women with T1D and 8332 controls remained at Year 2. Median BMI was higher in women with type 1 diabetes (25.5 vs 22.9 kg/m2 , P

Objective Lifestyle is the first-line treatment for women with polycystic ovary syndrome (PCOS). This study examines the physical activity (PA) levels and sedentary behaviours of women with and without PCOS, and their alignment with the PCOS PA guideline. Methods This cross-sectional study on women (aged 22-27 years) in the Australian Longitudinal Study on Women's Health was conducted in 2019 using data collected in 2017. Self-reported PA levels and total daily sitting time (ST) of women with (n = 7051) and without (n = 796) self-reported PCOS were presented, stratified by body mass index (BMI) and a combined overweight/obese group. Results 71.0% and 56.7% of the entire study cohort achieved PA levels recommended for weight maintenance and weight loss, respectively. Overall, PA levels were lower and ST was higher in women with than without PCOS. In each BMI category, similar proportions of women with and without PCOS met the PA guidelines but became lower as BMI category increased. Fewer overweight/obese group women with than without PCOS aligned with recommendations for weight maintenance (58.7% vs 65.7%, P = .003) or weight loss (45.1% vs 50.3%, P = .032). ST ≥8 h/d was observed in two-thirds of women with and without self-reported PCOS similarly before and after stratifying by BMI. Conclusion High sedentary behaviour was extremely prevalent. Although the majority of women met PA recommendations for weight maintenance, only one in two overweight/obese women met PA recommendation for weight loss. Overweight/obese women with PCOS were more likely to participate in insufficient PA and require increased support to achieve sustainable healthy lifestyle.

Polycystic ovary syndrome (PCOS) is associated with a higher risk for pregnancy and birth complications according to the specific features associated with PCOS. The features include obesity before and during pregnancy, hyperandrogenism, insulin resistance, infertility, cardiometabolic risk factors, and poor mental health. PCOS is not often recognized as a risk factor for poor pregnancy and birth outcomes in pregnancy care guidelines, while its associated features are. Pregnancy-related risk profile should ideally be assessed for modifiable risk factors (e.g., lifestyle and weight management) at preconception in women with PCOS. Hyperglycaemia should be screened using a 75-g oral glucose tolerance test at preconception or within the first 20 weeks of pregnancy if it has not been performed at preconception and should be repeated at 24-28 weeks of pregnancy. In the absence of evidence of benefit for strategies specific to women with PCOS, the international evidence-based guidelines for the assessment and management of PCOS recommend screening, optimizing, and monitoring risk profile in women with PCOS (at preconception, during and postpregnancy) consistent with the recommendations for the general population. Recommended factors include blood glucose, weight, blood pressure, smoking, alcohol, diet, exercise, sleep and mental health, emotional, and sexual health among women with PCOS. The guidelines recommend Metformin in addition to lifestyle for assisting with weight management and improving cardiometabolic risk factors, particularly in those with overweight or obesity. Letrozole is considered the first-line pharmacological treatment for anovulatory infertility in PCOS. Individualized approach should be considered in the management of pregnancy in PCOS.

Background: Polycystic ovary syndrome (PCOS) has a prevalence of 8–13%. Given the prevalence, diverse health impacts and variation in care, rigorous evidence‐based guidelines are needed in PCOS management. This systematic review with meta‐analyses aimed to investigate the effect of the combined oral contraceptive pill (COCP) and/or metformin in the management of hormonal and clinical features of PCOS, to inform international guidelines. Methods: Electronic databases were searched systematically from inception until 11 January 2017 to inform the guideline process. Eligible studies were randomized controlled trials which investigated the effect of COCPs and/or metformin alone or combined on hormonal and clinical features in women with PCOS. Outcomes were prioritized as critical for informing a decision about an intervention or important or not important, according to GRADE. Articles were assessed by one author against selection criteria, in consultation with a second author. Data were double extracted independently by four authors, and data quality appraisal was completed. Meta‐analyses were conducted, where appropriate. Results: Fifty‐six studies were eligible for inclusion. Outcomes prioritized by women and health professionals included the following: irregular cycles, insulin resistance, weight, BMI, thromboembolic events and gastrointestinal effects. In low‐quality evidence in adolescents, meta‐analyses demonstrated that metformin was better than COCP for BMI (mean difference [MD] −4.02 [−5.23, −2.81], P < 0.001); COCP was better than metformin for menstrual regulation (MD −0.19 [−0.25, −0.13], P < 0.00001). In low‐quality evidence in adults, meta‐analyses demonstrated that metformin was better than placebo for BMI (MD −0.48 [−0.94, −0.02], P = 0.04); metformin was better than COCP for fasting insulin (MD 4.00 [2.59, 5.41], P = 0.00001), whereas COCP was better than metformin for irregular cycles (MD 12.49 [1.34, 116.62], P = 0.03). Combined oral contraceptive pill alone was better than the combination with an anti‐androgen for BMI (MD −3.04 [−5.45, −0.64], P = 0.01). Metformin was associated with generally mild gastrointestinal adverse events. Differences in statistical significance were observed when outcomes were subgrouped by BMI. Conclusions: This review identified that COCP therapy has benefits for management of hyperandrogenism and menstrual regulation. Metformin combined with the COCP may be useful for management of metabolic features. There is minimal evidence of benefits of adding an anti‐androgen to COCP therapy. Metformin alone has benefits for adult women for management of weight, hormonal and metabolic outcomes, especially for women with BMI ≥ 25 kg/m². There is inadequate evidence to suggest the optimal COCP formulation, or dosing regimen and formulation of metformin.

Background Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women. Sleep disturbances may be more prevalent in PCOS. It is not known if this relationship is independent of other factors. Aim To examine the prevalence of sleep disturbances in a large community-based cohort study in women with and without PCOS and its relationship to clinical, demographic and comorbid factors. Methods We examined data from survey 5 (2009) of the Australian Longitudinal Study on Women's Health (n = 6578, n = 484 PCOS and n = 6094 non-PCOS). Sleep duration and disturbances were self-reported. Three classes of sleep pattern were derived during latent class analysis (normal sleep duration with average sleep, normal sleep duration with sleep symptoms and short sleep duration with sleep symptoms) and compared between women with and without PCOS using multivariate regression, adjusting for body mass index (BMI), depressive symptoms, demographic and comorbid factors. Results Women with PCOS had similar sleep duration but were more likely to experience difficulty sleeping often (RRR 1.67, 1.20-2.33, P = 0.003) and sometimes (RRR 1.39, 1.07-1.80, P = 0.015), with restless sleep reported occasionally (RRR, 1.35 1.00-1.83, P = 0.049). They reported severe tiredness often (RRR 1.48, 95% CI 1.08-2.04, P = 0.016) and described more sleep difficulties within the last 12 months (OR 1.29, 1.04-1.60, P = 0.018) on adjusted analyses. Compared to the class of average sleep duration with no sleep disturbances, PCOS was associated with increased relative risk of having average sleep duration with sleep symptoms (RRR 1.40, 95%CI 1.11-1.77, P = 0.004) and short sleep duration with sleep symptoms (RRR 1.46, 95%CI 1.07-1.99, P = 0.016) on adjusted analyses. Conclusion Sleep disturbances are more prevalent amongst women with PCOS after adjusting for BMI, depressive symptoms, demographic and comorbid factors. Targeted screening and management of sleep disturbances is warranted in PCOS.

BACKGROUND Polycystic ovary syndrome (PCOS) affects up to 13% women and is associated with significant complications. The quality of evidence supporting the recommendations on treatment of nonreproductive outcomes in PCOS is unknown. OBJECTIVE To summarize and appraise the methodological quality of systematic reviews and meta-analyses evaluating pharmacological and surgical treatments for nonreproductive outcomes in PCOS. METHODS A literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed from inception until 15th of September 2017. Article selection, data extraction and quality appraisal of included reviews were performed in duplicate. A narrative synthesis of the findings was conducted. RESULTS This overview included 31 reviews. The quality was low for 7 (23%), moderate for sixteen (52%) and high for 8 reviews (26%). Two reviews assessed psychological outcomes. Metformin improved anthropometric (7 of 10 reviews), metabolic (4 of 14 reviews) and endocrine outcomes (3 of twelve reviews). Thiazolidinediones improved metabolic (2 of 5 reviews) and endocrine outcomes (one of 5 reviews) but worsened weight gain (5 of 5 reviews). Combined oral contraceptive pill (COCP) improved clinical hyperandrogenism (2 of 2 reviews). Statins improved lipid profile (3 of 3 reviews) and testosterone level (2 of 3 reviews). There was no conclusive evidence from included systematic reviews regarding the use of other interventions. CONCLUSIONS There is reliable evidence regarding the use of metformin for anthropometric outcomes and COCPs for hyperandrogenism in women with PCOS but not for other interventions. There is significant gap in knowledge regarding the management of psychological outcomes in women with PCOS which needs further evaluation.

Although there is a growing body of literature reporting that pregnancies in women with polycystic ovary syndrome (PCOS) are associated with greater complications than those without PCOS, methodological differences across studies make these results difficult to consolidate. This narrative review outlines potential mechanisms involved in adverse pregnancy outcomes in PCOS and the nature of the complications. It covers limitations of current evidence and future research directions. Future research should include prospective studies with phenotypic stratification of PCOS and matching or consideration of specific PCOS manifestations and risk factors specific to each pregnancy complication. This review also emphasizes the importance of following a healthy lifestyle for women with PCOS and of individualized care according to overall risk factors for pregnancy complications.

SummaryObjective Polycystic ovary syndrome (PCOS) is a complex endocrine disorder associated with insulin resistance, hyperandrogenism, obesity, altered gonadotrophin release and anovulatory infertility. Anti-Mullerian hormone (AMH) has been proposed as a marker of ovarian function and fertility. Across a cohort of lean and overweight women with and without PCOS, we investigated the association of AMH with insulin resistance and body composition using gold standard measures. A secondary aim was to examine whether AMH was useful to determine PCOS status. Design Cross-sectional study. Patients A total of 22 lean and 21 overweight women with PCOS and 19 lean and 16 overweight non-PCOS healthy controls were recruited. PCOS was diagnosed based on the Rotterdam criteria. Measurements Euglycaemic-hyperinsulinaemic clamp for assessing insulin resistance, dual energy X-ray absorptiometry and computed tomography for assessing adiposity, and blood sampling for the assessment of androgens, gonadotrophins and AMH. Results Anti-Mullerian hormone levels were increased in women with PCOS (P

OBJECTIVE Polycystic ovary syndrome (PCOS) affects 12-21% of women. Women with PCOS exhibit clustering of metabolic features. We applied rigorous statistical methods to further understand the interplay between PCOS and metabolic features including insulin resistance, obesity and androgen status. DESIGN Retrospective cross-sectional analysis. PATIENTS Women with PCOS attending reproductive endocrine clinics in South Australia for the treatment of PCOS (n = 172). Women without PCOS (controls) in the same Australian region (n = 335) from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), a national population-based study (age- and BMI-matched within one standard deviation of the PCOS cohort). MEASUREMENTS The factor structure for metabolic syndrome for women with PCOS and control groups was examined, specifically, the contribution of individual factors to metabolic syndrome and the association of hyperandrogenism with other metabolic factors. RESULTS Women with PCOS demonstrated clustering of metabolic features that was not observed in the control group. Metabolic syndrome in the PCOS cohort was strongly represented by obesity (standardized factor loading = 0·95, P < 0·001) and insulin resistance factors (loading = 0·92, P < 0·001) and moderately by blood pressure (loading = 0·62, P < 0·001) and lipid factors (loading = 0·67, P = 0·002). On further analysis, the insulin resistance factor strongly correlated with the obesity (r = 0·70, P < 0·001) and lipid factors (r = 0·68, P < 0·001) and moderately with the blood pressure factor (loading = 0·43, P = 0·002). The hyperandrogenism factor was moderately correlated with the insulin resistance factor (r = 0·38, P < 0·003), but did not correlate with any other metabolic factors. CONCLUSIONS PCOS women are more likely to display metabolic clustering in comparison with age- and BMI-matched control women. Obesity and insulin resistance, but not androgens, are independently and most strongly associated with metabolic syndrome in PCOS.

SummaryObjective Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic complications. Metabolic biomarkers with roles in obesity, glycaemic control and lipid metabolism are potentially relevant in PCOS. The aim was to investigate metabolic biomarkers in lean and overweight women with and without PCOS and to determine whether any biomarker was able to predict insulin resistance in PCOS. Design Cross-sectional study. Patients Eighty-four women (22 overweight and 22 lean women with PCOS, 18 overweight and 22 lean women without PCOS) were recruited from the community and categorized based on PCOS and BMI status. Measurements Primary outcomes were metabolic biomarkers [ghrelin, resistin, visfatin, glucagon-like peptide-1 (GLP-1), leptin, plasminogen activator inhibitor -1 (PAI-1), glucose-dependent insulinotropic polypeptide (GIP) and C-Peptide] measured using the Bio-Plex Pro Diabetes assay and insulin sensitivity as assessed by glucose infusion rate on euglycaemic–hyperinsulinaemic clamp. Results The biomarkers C-peptide, leptin, ghrelin and visfatin were different between overweight and lean women, irrespective of PCOS status. The concentration of circulating biomarkers did not differ between women with PCOS diagnosed by the Rotterdam criteria or National Institute of Health criteria. PAI-1 was the only biomarker that significantly predicted insulin resistance in both control women (P = 0·04) and women with PCOS (P = 0·01). Conclusions Biomarkers associated with metabolic diseases appear more strongly associated with obesity rather than PCOS status. PAI-1 may also be a novel independent biomarker and predictor of insulin resistance in women with and without PCOS.