Background/Objectives: Polycystic Ovary Syndrome (PCOS) is a multifactorial endocrine disorder with significant clinical and reproductive implications. Identifying dose-response relationships between clinical, physical, and reproductive factors and PCOS can enhance diagnostic accuracy and inform treatment strategies. This study utilized a data-driven approach to analyze the associations between key factors, including age, weight, menstrual cycle length, Anti-Mullerian Hormone (AMH) levels, and follicle count, with PCOS prevalence. Methods: A retrospective analysis was conducted on a dataset of 539 participants to determine the optimal ranges of these factors associated with an increased likelihood of PCOS diagnosis. Statistical analyses were conducted using Python, including correlation matrix, univariate and multivariate logistic regression, and dose-response evaluations. Results: Our findings demonstrated that the risk of PCOS increases positively in women under 32 years of age. AMH levels above 4.18 ng/mL were strongly associated with PCOS, suggesting that higher AMH levels may reflect excessive follicular activity rather than enhanced ovarian function. Weight was positively correlated with PCOS, emphasizing the role of metabolic disturbances in its pathophysiology. Additionally, menstrual cycle length exhibited a non-linear association with PCOS, with both shortened and prolonged cycles being indicative of hormonal dysregulation. A higher follicle count was consistently linked to PCOS, reinforcing its diagnostic significance. Conclusions: This study provides evidence of non-linear dose-response relationships between PCOS and clinical, physical, and reproductive factors. The proposed optimal ranges may serve as valuable reference points for clinicians, aiding in early diagnosis and personalized management strategies for women with PCOS.

To estimate the risk of cardiovascular (CV) events (primary aim) and to evaluate the long-term variation in CV risk factors in a Caucasian population of women with polycystic ovary syndrome (PCOS).

Matched cohort prospective study based on 10 years of follow-up.

One hundred twenty Caucasian women with PCOS diagnosed by the National Institutes of Health criteria in reproductive age were assessed at baseline (2009) and at the end of follow-up (2020) for major and minor CV events and CV risk factors. Five controls were exactly matched by age and the presence/absence of type 2 diabetes with each participant at baseline (total number = 600) and followed up to evaluate the relative risk of PCOS for CV events. Change in epicardial fat thickness (EFT) was also analysed.

The mean age of patients with PCOS at follow-up was 51.9 ± 7.7 years. No major CV events were detected in PCOS patients (0% vs. 2% among controls), and the incidence of any minor CV events was 4.2% vs. 2.3% among controls (P = .340). The percentage of most CV risk factors (obesity, type 2 diabetes, hypertension, dyslipidaemia, and carotid intima media thickness ≥1 mm with or without plaques with non-critical stenosis) increased. By contrast, both short- and long-axis EFTs and smoking decreased markedly.

Caucasian patients with PCOS do not have an increased risk for CV events during the late reproductive or early post-menopausal period, despite the increase in most CV risk factors, except for EFT that markedly decreases. Further studies are needed to determine the role of EFT on CV risk in PCOS.

Per- and polyfluoroalkyl substances (PFAS) may impact ovarian folliculogenesis and steroidogenesis, but whether prenatal exposure may impact offspring reproductive health is unknown. This study examines the extent to which maternal PFAS plasma concentrations during pregnancy are associated with polycystic ovary syndrome (PCOS) and related characteristics in female offspring.

We studied 322 mother-daughter pairs in Project Viva, a Boston-area longitudinal pre-birth cohort enrolled 1999-2002. We examined associations of maternal prenatal (median: 9.6 weeks gestation) plasma concentrations of six PFAS (log2 transformed) with PCOS and related characteristics among daughters during mid-to-late adolescence. We estimated the associations of single PFAS and PFAS as a mixture with each outcome, using logistic regression and quantile g-computation, respectively, adjusting for parity, and maternal sociodemographic and other lifestyle/health factors.

Among the 322 mother-daughter pairs, the majority of mothers identified as non-Hispanic White and had a college degree, and 13% of daughters had either self-reported PCOS or probable PCOS based on irregular menstrual cycles and clinical or biochemical markers of hyperandrogenism. Among all daughters, there were 27% with irregular menstrual cycles, 34% with hirsutism, and 6% with moderate-to-severe acne. When fully adjusted for confounders, per doubling of maternal 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) concentration was associated with higher odds of self-reported PCOS [OR (95% CI) = 2.66 (1.18, 5.99)], and per doubling of maternal perfluorononanoate (PFNA) concentration was associated with higher odds of moderate-to-severe acne [OR (95% CI) = 2.33 (1.09, 4.99)] in daughters with or without irregular menstrual cycles. We found no associations of the mixture of six PFAS with PCOS or related traits.

Our findings suggest a positive association between maternal concentrations of EtFOSAA and PCOS in their daughters during mid-to-late adolescence, although future studies with larger sample size and extended follow-up across the reproductive life-course are needed.

To study measures of endothelial health, cardiovascular risk, and cellular aging between patients with polycystic ovary syndrome (PCOS) and a reproductive age normative cohort.

Cross-sectional study.

Community-based patients with PCOS and a normative ovarian aging cohort as controls, aged ≤45 years at the time of evaluation.

Noninvasive measure of endothelial health measured by the EndoPAT reactive hyperemia index.

Reactive hyperemia index as measure of endothelial health. The secondary outcomes included Framingham score, telomere length, and mitochondrial deoxyribonucleic acid copy number from leukocyte cells.

Our cohort included 63 participants with PCOS and 130 non-PCOS participants. The mean age was significantly lower in the PCOS cohort (33.1; standard deviation, 4.7 years) than in the non-PCOS cohort (40.8; standard deviation, 2.9 years). In multivariable-adjusted models, we found that PCOS was significantly associated with endothelial dysfunction as both categorical (odds ratio for PCOS, 0.31; 95% confidence interval [CI], 0.10-0.97) and continuous (PCOS coefficient, -0.37; 95% CI, -0.69 to -0.05) outcomes. For secondary outcomes, PCOS status was not significantly associated with mitochondrial deoxyribonucleic acid (PCOS coefficient, -48.1; 95% CI, -175.0 to 78.9), telomere length (PCOS coefficient, 0.05; 95% CI, -0.05 to 0.15), Framingham score (PCOS coefficient, 0.002; 95% CI, -0.01 to 0.02), or metabolic syndrome (odds ratio for PCOS, 1.29; 95% CI, 0.31-5.44).

Our findings suggest that patients with PCOS have impaired endothelial function compared with non-PCOS patients, although measures of cellular aging and cardiovascular risk as measured by the Framingham score did not differ between the cohorts.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged females, and women with PCOS are at increased risk for endometrial cancer (EndoCA), the most common gynecological malignancy.

Our study sought to assess the economic burden associated with EndoCA in PCOS.

Using PRISMA systematic review guidelines, we evaluated studies on EndoCA rates in patients with PCOS. Excluded studies were reviews and case reports, those with nonhuman subjects, without controls, without full text available, or reporting solely on other conditions. Selected studies were assessed for quality using the Newcastle-Ottawa Scale. Meta-analysis used DerSimonian-Laird random effects model to assess pooled risk ratio (RR). Excess cost was assessed in US dollars (USD).

Of 98 studies screened, 9 were included. Pooled RR for EndoCA in PCOS was 3.46 (95% CI, 2.28-5.23), P ≤ .001. In the United States, prevalence of EndoCA in patients with PCOS in 2020 was 1.712%, compared with a baseline estimated prevalence in all women of 0.489%. The excess prevalence of EndoCA attributable to PCOS was 1.223%, approximately 98 348 affected women. A population attributable fraction of EndoCA for PCOS was 24.4%. Given estimated costs of EndoCA exceeding $1.9 billion (in 2023 USD), the economic burden of EndoCA attributable to PCOS exceeds $467 million/year.

The excess annual US healthcare cost for EndoCA attributable to PCOS exceeds $467 million/year (2023 USD). Although a concerning morbidity of PCOS, it is notable that the economic burden of EndoCA attributable to the disorder represents only a small fraction of its total healthcare burden.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine anomalies among females of reproductive age, highlighted by hyperandrogenism. PCOS is multifactorial as it can be associated with obesity, insulin resistance, low-grade chronic inflammation, and dyslipidemia. PCOS also leads to dysbiosis by lowering microbial diversity and beneficial microbes, such as Faecalibacterium, Roseburia, Akkermenisa, and Bifidobacterium, and by causing a higher load of opportunistic pathogens, such as Escherichia/Shigella, Fusobacterium, Bilophila, and Sutterella. Wherein, butyrate producers and Akkermansia participate in the glucose uptake by inducing glucagon-like peptide-1 (GLP-1) and glucose metabolism, respectively. The abovementioned gut microbes also maintain the gut barrier function and glucose homeostasis by releasing metabolites such as short-chain fatty acids (SCFAs) and Amuc_1100 protein. In addition, PCOS-associated gut is found to be higher in gut-microbial enzyme β-glucuronidase, causing the de-glucuronidation of conjugated androgen, making it susceptible to reabsorption by entero-hepatic circulation, leading to a higher level of androgen in the circulatory system. Overall, in PCOS, such dysbiosis increases the gut permeability and LPS in the systemic circulation, trimethylamine N-oxide (TMAO) in the circulatory system, chronic inflammation in the adipose tissue and liver, and oxidative stress and lipid accumulation in the liver. Thus, in women with PCOS, dysbiosis can promote the progression and severity of type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). To alleviate such PCOS-associated complications, microbial therapeutics (probiotics and fecal microbiome transplantation) can be used without any side effects, unlike in the case of hormonal therapy. Therefore, this study sought to understand the mechanistic significance of gut microbes in PCOS and associated comorbidities, along with the role of microbial therapeutics that can ease the life of PCOS-affected women.

The present study aimed to clarify the conflicting association of premenopausal hyperandrogenaemia (HA) with the development of hypertension and cardiovascular disease (CVDs) in women.

A population-based cohort study including 5889 women.

The association of serum testosterone (T), sex hormone-binding globulin (SHBG), and free androgen index (FAI) at age 31 with blood pressure (BP) and hypertension (BP ≥ 140/90 mmHg and/or use of antihypertensive medication) at ages 31 and 46 and with CVDs (angina pectoris [AP] and/or acute myocardial infarction [AMI] n = 74, transitory cerebral ischaemia and/or stroke n = 150) and combined CVD events (AP, AMI, stroke, heart failure, or CVD mortality n = 160) by age 53 was investigated.

T and FAI were positively associated with systolic and diastolic BP at ages 31 and 46 in the multivariable model. Compared to their lowest quartile, the highest quartiles of T and FAI were positively associated with hypertension at age 31 in the multivariable model. During the 22-year follow-up, FAI was positively associated with increased risk of AP/AMI (hazard ratio [HR]: 2.02, 95% CI: 1.06-3.85) and overall CVD events or mortality (HR: 1.54, 95% CI: 1.02-2.33) in the unadjusted models. However, the significance disappeared after adjusting for body mass index (BMI).

Women with HA at premenopausal age had an elevated risk of hypertension, and together with BMI, increased risk of CVD events and CVD mortality during the 22-year follow-up. However, because of several study limitations regarding ethnicity and BMI characteristics, a longer follow-up of this cohort and future studies in ethnically diverse populations are needed to verify the results.

Polycystic ovary syndrome (PCOS) is the most prevalent female endocrinopathy. Although increased cardiovascular risk factors are well established for the syndrome, PCOS remains overlooked within the realm of cardiology. We conducted a systematic review and meta-analysis on the risk of clinical cardiovascular disease (CVD) events in women with PCOS to inform the 2023 International Evidence-Based PCOS Guideline.

A systematic review and meta-analysis was conducted comparing the risk of clinical CVD events in women with and without PCOS. Medline (Ovid), PsycInfo (Ovid), EMBASE, All EBM (Ovid), and CINAHL were searched from January 1, 2017, until March 1, 2023, to update the 2018 PCOS Guideline. Pooled odds ratios (ORs), incidence rate ratios (IRRs), and hazard ratios (HRs) were calculated. Twenty studies involving 1.06 million women (369 317 with PCOS and 692 963 without PCOS) were included. PCOS was associated with higher risk of composite CVD (OR, 1.68 [95% CI, 1.26-2.23]; I2 = 71.0%), composite ischemic heart disease (OR, 1.48 [95% CI, 1.07-2.05]; I2 = 81.0%), myocardial infarction (OR, 2.50 [95% CI, 1.43-4.38]; I2 = 83.3%), and stroke (OR, 1.71 [95% CI, 1.20-2.44]; I2 = 81.4%). The relationship with cardiovascular mortality was less clear (OR, 1.19 [95% CI, 0.53-2.69]; I2 = 0%). Meta-analyses of IRRs support these findings. Results from pooled HRs were limited by the small number of studies and significant heterogeneity.

This review provides evidence and highlights the importance of recognizing PCOS as a significant risk factor for CVD morbidity. The 2023 International Evidence-Based PCOS Guideline now recommends awareness of increased CVD risk and comprehensive risk assessment in PCOS to help mitigate the burden of CVD in this common and high-risk condition.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. It has been associated with metabolic, reproductive, and psychiatric disorders. Despite its association with insulin resistance (IR) and cardiovascular disease (CVD) risk factors, the association between PCOS and CVD outcomes has been conflicting. This review reports the updated evidence between PCOS, insulin resistance, and CVD events.

IR is highly prevalent occurring in 50 to 95% of general and obese PCOS women. The etiology of PCOS involves IR and hyperandrogenism, which lead to CVD risk factors, subclinical CVD, and CVD outcomes. Multiple studies including meta-analysis confirmed a strong association between PCOS and CVD events including ischemic heart disease, stroke, atrial fibrillation, and diabetes, particularly among premenopausal women, and these associations were mediated by metabolic abnormalities. PCOS is highly familial and has substantial CVD risk and transgenerational effects regardless of obesity. A personalized approach to the CVD risk assessment and management of symptom manifestations should be conducted according to its phenotypes. Lifestyle modifications and reduction in environmental stressors should be encouraged for CVD prevention among PCOS women.

Cardiometabolic risk factors are common in women with polycystic ovary syndrome (PCOS) during reproductive years. The aim of this study was to determine the impact of aging on cardiometabolic risk of the syndrome by examining women who had previously been diagnosed to have PCOS or to be healthy in an unselected population in 2009.

Forty-one women with PCOS who were diagnosed and phenotyped according to the Rotterdam criteria and 43 age- and body mass index (BMI)-matched healthy women from the same unselected cohort.

All participants were evaluated by structured interview, physical examination, anthropometric, hormonal and biochemical measurements. Additionally, body composition analyses and echocardiographic assessments of 30 women with PCOS and 30 control women were conducted at 13 years of follow-up.

There was no difference between the patient and the control groups in terms of anthropometric and body composition measures and metabolic parameters. Echocardiographic assessment showed similar systolic functions, strain measurements and epicardial fat measurements between the groups. PCOS patients still had higher levels of total testosterone, free androgen index (FAI) and dehydroepiandrosterone sulfate (DHEAS) levels compared to controls. Epicardial fat thickness showed positive correlations with BMI, total and truncal body fat, homeostatic model assessment for insulin resistance (HOMA-IR) and free androgen index (FAI).

Aging women with PCOS in the population have higher androgen levels and similar cardiometabolic risk profile compared to age- and BMI-matched healthy women. Epicardial fat thickness, a marker of cardiometabolic risk, appear to be associated with hyperandrogenism. Further research is needed on larger community-based cohorts where older patients are assessed with a longer follow-up.

Polycystic ovary syndrome (PCOS) is the most common metabolic-endocrine disorder impacting the health and quality of life of women over the lifespan. Evidence-based data on the scope of adverse health outcomes in those affected by PCOS is critical to improve healthcare and quality of life in this population. The aim of this study was to determine the prevalence of adverse health outcomes in those with PCOS compared to age-matched controls.

We conducted a retrospective observational case-control study in those diagnosed with PCOS and age-matched controls using the Alberta Health Services Health Analytics database and the International Classification of Diseases, for the period from 2002-2018 in Alberta, Canada.

The cohort consisted of n = 16,531 exposed PCOS cases and n = 49,335 age-matched un-exposed controls. The prevalences of hypertension, renal disease, gastrointestinal disease, eating disorders, mental illness, depression-anxiety, rheumatoid arthritis, respiratory infections, and all malignancies were 20%-40% (P < 0.0001) higher in those with PCOS, compared to controls. The prevalence of obesity, dyslipidemia, nonalcoholic fatty liver disease, and type 2 diabetes was 2-3 fold higher in those with PCOS (P < 0.001). Cardiovascular, cerebrovascular, and peripheral vascular disease were 30%-50% higher, and they occurred 3-4 years earlier in those with PCOS (P < 0.0001); a 2-fold higher prevalence of dementia occurred in those with PCOS, compared to controls.

These findings provide evidence that PCOS is associated with a higher prevalence of morbidities over the lifespan, and the potential scope of the healthcare burden in women affected by PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women during the fertile period. Women with PCOS have an increased risk of developing major cardiovascular risk factors during the fertile period: obesity, impaired glucose tolerance, diabetes mellitus, dyslipidemia, and metabolic syndrome. The possible effect of PCOS on cardiovascular disease (CVD) has been reported in different studies, but the results are not clear for several reasons. Indeed, most of the studies analyzed a cohort of fertile women who, given their relatively young age, have a low frequency of cardiovascular diseases. In addition, longitudinal studies have a short follow-up period, insufficient to draw firm conclusions on this topic. Finally, pharmacological treatment is limited by the lack of specific drugs available to specifically treat PCOS. In this review, we report on studies that analyzed the possible effect of PCOS on the most common CVD (hypertension, arterial stiffness, atherosclerosis, and cardiovascular event) and available drugs used to reduce CVD in PCOS women.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder experienced by women. PCOS is a lifelong condition associated with reproductive, metabolic, and psychological presentations. PCOS is also linked with increased prevalence of cardiometabolic risk factors. While an association between body weight and PCOS has been noted, cardiometabolic risk factors are prevalent in individuals with PCOS across body weights. Currently, no consensus exists as to the most appropriate lifestyle strategy for mitigating cardiometabolic risk in PCOS. A large proportion of the literature is focused on weight loss for individuals with PCOS who are overweight or experience obesity, despite PCOS being prevalent across body sizes. The aim of this narrative review is to assess dietary and lifestyle interventions aimed at reducing cardiometabolic risk in individuals with PCOS across body sizes. A total of 51 articles are included in this review. Overall, randomized controlled trials are limited and most studies focus on weight loss, excluding individuals classified within a healthy body weight range. Studies that modified the dietary pattern without an energy deficit saw improvements in cardiometabolic risk. Thus, less restrictive dietary approaches may be effective at reducing cardiometabolic risk in this population. This review also highlights the need for more sustainable lifestyle interventions that meet the needs of individuals with PCOS of varying body weights.

Polycystic ovary syndrome (PCOS) is a complex syndrome that affects menstrual regularity, causes hyperandrogenism, increases the risk of metabolic dysfunction and infertility, and is associated with higher rates of mental health disorders. The symptoms of PCOS are unique to each individual and will evolve throughout their reproductive lifespan and beyond. Thus, care should be personalized and provided by an appropriate team of multidisciplinary physicians and clinicians, such as dieticians and psychologists.

Current knowledge about the consequences of PCOS during the late reproductive years and after menopause is limited.

We performed a systematic review and meta-analysis of data on the pathophysiology, clinical manifestations, diagnosis, prognosis, and treatment of women ≥45 years of age-peri- or postmenopausal-with PCOS.

Studies published up to 15 April 2023, identified by Entrez-PubMed, EMBASE, and Scopus online facilities, were considered. We included cross-sectional or prospective studies that reported data from peri- or postmenopausal patients with PCOS and control women with a mean age ≥45 years. Three independent researchers performed data extraction. Meta-analyses of quantitative data used random-effects models because of the heterogeneity derived from differences in study design and criteria used to define PCOS, among other confounding factors. Sensitivity analyses restricted the meta-analyses to population-based studies, to studies including only patients diagnosed using the most widely accepted definitions of PCOS, only menopausal women or only women not submitted to ovarian surgery, and studies in which patients and controls presented with similar indexes of weight excess. Quality of evidence was assessed using the GRADE system.

The initial search identified 1400 articles, and another six were included from the reference lists of included articles; 476 duplicates were deleted. We excluded 868 articles for different reasons, leaving 37 valid studies for the qualitative synthesis, of which 28 studies-published in 41 articles-were considered for the quantitative synthesis and meta-analyses. Another nine studies were included only in the qualitative analyses. Compared with controls, peri- and postmenopausal patients with PCOS presented increased circulating total testosterone (standardized mean difference, SMD 0.78 (0.35, 1.22)), free androgen index (SMD 1.29 (0.89, 1.68)), and androstenedione (SMD 0.58 (0.23, 0.94)), whereas their sex hormone-binding globulin was reduced (SMD -0.60 (-0.76, -0.44)). Women with PCOS showed increased BMI (SMD 0.57 (0.32, 0.75)), waist circumference (SMD 0.64 (0.42, 0.86)), and waist-to-hip ratio (SMD 0.38 (0.14, 0.61)) together with increased homeostasis model assessment of insulin resistance (SMD 0.56 (0.27, 0.84)), fasting insulin (SMD 0.61 (0.38, 0.83)), fasting glucose (SMD 0.48 (0.29, 0.68)), and odds ratios (OR, 95% CI) for diabetes (OR 3.01 (1.91, 4.73)) compared to controls. Women with PCOS versus controls showed decreased HDL concentrations (SMD -0.32 (-0.46, -0.19)) and increased triglycerides (SMD 0.31 (0.16, 0.46)), even though total cholesterol and LDL concentrations, as well as the OR for dyslipidaemia, were similar to those of controls. The OR for having hypertension was increased in women with PCOS compared with controls (OR 1.79 (1.36, 2.36)). Albeit myocardial infarction (OR 2.51 (1.08, 5.81)) and stroke (OR 1.75 (1.03, 2.99)) were more prevalent in women with PCOS than controls, the ORs for cardiovascular disease as a whole, coronary artery disease as a whole, breast cancer and age at menopause, were similar in patients and controls. When restricting meta-analysis to studies in which women with PCOS and controls had a similar mean BMI, the only difference that retained statistical significance was a decrease in HDL-cholesterol concentration in the former and, in the two studies in which postmenopausal women with PCOS and controls had similar BMI, patients presented with increased serum androgen concentrations, suggesting that hyperandrogenism persists after menopause, regardless of obesity.

Hyperandrogenism appeared to persist during the late-reproductive years and after menopause in women with PCOS. Most cardiometabolic comorbidities were driven by the frequent coexistence of weight excess and PCOS, highlighting the importance of targeting obesity in this population. However, the significant heterogeneity among included studies, and the overall low quality of the evidence gathered here, precludes reaching definite conclusions on the issue. Hence, guidelines derived from adequately powered prospective studies are definitely needed for appropriate management of these women.

Understanding the cardiovascular disease (CVD) risk for women with polycystic ovary syndrome (PCOS) at reproductive age is crucial. To investigate this, we compared the cardiometabolic profiles of different PCOS groups over a median interval of 15.8 years. The study focused on three groups: (1) women with PCOS who were hyperandrogenic at both initial and follow-up screening (HA-HA), (2) those who transitioned from hyperandrogenic to normoandrogenic (HA-NA), and (3) those who remained normoandrogenic (NA-NA). At initial and follow-up screenings, both HA-HA and HA-NA groups showed higher body mass indexes compared to the NA-NA group. Additionally, at follow-up, the HA-HA and HA-NA groups exhibited higher blood pressure, a higher prevalence of hypertension, elevated serum triglycerides and insulin levels, and lower levels of HDL cholesterol compared to the NA-NA group. Even after adjusting for BMI, significant differences persisted in HDL cholesterol levels and hypertension prevalence among the groups (HA-HA: 53.8%, HA-NA: 53.1%, NA-NA: 14.3%, p < 0.01). However, calcium scores and the prevalence of coronary plaques on CT scans were similar across all groups. In conclusion, women with PCOS and hyperandrogenism during their reproductive years exhibited an unfavorable cardiometabolic profile during their post-reproductive years, even if they changed to a normoandrogenic status.

Gestational diabetes mellitus (GDM) and polycystic ovarian syndrome (PCOS) represent two of the highest risk factors for development of type 2 diabetes mellitus in young women. As these increasingly common conditions generally affect younger women, early detection of dysglycemia is key if preventative measures are to be effective. While international guidance recommends screening for type 2 diabetes, current screening strategies suffer from significant challenges.First, guidance lacks consensus in defining which tests to use and frequency of monitoring, thereby sending mixed messages to healthcare professionals.Second, conformity to guidance is poor, with only a minority of women having tests at the recommended frequency (where specified). Approaches to improve conformity have focused on healthcare related factors (largely technology driven reminder systems), but patient factors such as convenience and clear messaging around risk have been neglected.Third, and most critically, current screening strategies are too generic and rely on tests that become abnormal far too late in the trajectory towards dysglycemia to offer opportunities for effective preventative measures. Risk factors show wide interindividual variation, and insulin sensitivity and β cell function are often abnormal during pre-diabetes stage, well before frank diabetes.New, consistent, targeted screening strategies are required that incorporate early, prevention focused testing and personalised risk stratification.

Polycystic ovary syndrome (PCOS), affecting more than every 10th woman of reproductive age, is associated with increased risk factors for cardiovascular disease (CVD). Most knowledge regarding longtime consequences concerning morbidity is based on women where ovarian wedge resection (WR) was used as a surgical treatment, a method not used today. The aim of this study was to compare women with PCOS who had and had not undergone WR, regarding risk factors for CVD. The hypothesis was that women who had undergone WR had a more severe PCOS phenotype, and that this cohort thus had more associated CVD risk factors compared with women diagnosed through non-invasive methods.

A cross-sectional study was performed. A PCOS cohort who underwent WR in the 1950-60 s (n = 27) were compared with a PCOS cohort diagnosed by NIH-criterions in the 1990s without WR (n = 32). Both cohorts were examined at perimenopausal age.

No differences were seen in prevalence of hypertension, obesity or type 2 diabetes mellitus (T2DM) between the women with PCOS with or without WR, respectively. The results were persistent irrespective of the lower mean BMI in the WR group, 26.4 vs. 30.7 kg/m2, p = 0.01. In the stratified group of overweight and obese, there was no difference in T2DM 27% vs 25% or hypertension 27% vs 25%, in WR and non-WR women with PCOS, respectively. The cohort diagnosed through WR had higher free androgen index (6.3 vs. 2.1, p < 0.01) and total testosterone (2.20 vs. 0.99 nmol/L, p < 0.01).

No differences in CVD risk factors were found in perimenopausal women with PCOS with or without a previous WR, and irrespective of body weight. The results indicate that CVD morbidity and mortality from studies in women with PCOS who have undergone WR are generalizable to women with PCOS who have not undergone WR.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of childbearing age. The etiology of PCOS is multifactorial, and current treatments for PCOS are far from satisfactory. Recently, an imbalanced autonomic nervous system (ANS) with sympathetic hyperactivity and reduced parasympathetic nerve activity (vagal tone) has aroused increasing attention in the pathogenesis of PCOS. In this paper, we review an innovative therapy for the treatment of PCOS and related co-morbidities by targeting parasympathetic modulation based on non-invasive transcutaneous auricular vagal nerve stimulation (ta-VNS). In this work, we present the role of the ANS in the development of PCOS and describe a large number of experimental and clinical reports that support the favorable effects of VNS/ta-VNS in treating a variety of symptoms, including obesity, insulin resistance, type 2 diabetes mellitus, inflammation, microbiome dysregulation, cardiovascular disease, and depression, all of which are also commonly present in PCOS patients. We propose a model focusing on ta-VNS that may treat PCOS by (1) regulating energy metabolism via bidirectional vagal signaling; (2) reversing insulin resistance via its antidiabetic effect; (3) activating anti-inflammatory pathways; (4) restoring homeostasis of the microbiota-gut-brain axis; (5) restoring the sympatho-vagal balance to improve CVD outcomes; (6) and modulating mental disorders. ta-VNS is a safe clinical procedure and it might be a promising new treatment approach for PCOS, or at least a supplementary treatment for current therapeutics.

An estimated 15-20% of reproductive-age women are affected by polycystic ovary syndrome (PCOS). PCOS is associated with substantial metabolic and cardiovascular long-term consequences. In young women with PCOS, several cardiovascular risk factors may be found, including chronic inflammation, high blood pressure, and elevated leukocytes. These women are at an increased risk of cardiovascular diseases (CVD), not only during the reproductive years, but also with aging and menopause; therefore, the early prevention and treatment of future cardiovascular adverse effects are necessary. The fundamental characteristic of PCOS is hyperandrogenemia, which is associated with increased pro-inflammatory cytokines and T lymphocytes. Whether these factors play a role in the pathophysiology of hypertension, a risk factor of CVD, due to PCOS is not well established. This review will briefly discuss how a modest increase in androgens in females is linked to the development of hypertension through pro-inflammatory cytokines and T lymphocyte subsets and the promotion of renal injury. Moreover, it reveals a few existing research gaps in this area, including the lack of specific therapy directed at androgen-induced inflammation and immune activation, thus emphasizing the necessity to explore the systemic inflammation in women with PCOS to halt the inevitable inflammatory process targeting the underlying abnormalities of CVD.

Social determinants of health (SDOH) are the social conditions in which people are born, live, and work. SDOH offers a more inclusive view of how environment, geographic location, neighborhoods, access to health care, nutrition, socioeconomics, and so on are critical in cardiovascular morbidity and mortality. SDOH will continue to increase in relevance and integration of patient management, thus, applying the information herein to clinical and health systems will become increasingly commonplace. This state-of-the-art review covers the 5 domains of SDOH, including economic stability, education, health care access and quality, social and community context, and neighborhood and built environment. Recognizing and addressing SDOH is an important step toward achieving equity in cardiovascular care. We discuss each SDOH within the context of cardiovascular disease, how they can be assessed by clinicians and within health care systems, and key strategies for clinicians and health care systems to address these SDOH. Summaries of these tools and key strategies are provided.

<b>Background and Objective:</b> The pathogenesis of PCOS, which affects 5-15% of women of reproductive age, is still poorly understood and which characteristic might be considered essential for its diagnosis is still unknown. This study aimed to determine the significance and relationship between Anti-Mullerian Hormone (AMH) and other infertility hormones in the Polycystic Ovarian Syndrome (PCOS) diagnosis. <b>Materials and Methods:</b> This study involves 200 women who visited Al-Ramadi Maternity and Child Teaching Hospital in Al-Ramadi, Iraq from October, 2022 to May, 2023. Study participants included 50 women as controls and 150 women with PCOS who were diagnosed using the Rotterdam criteria. The clinical history included oligomenorrhea and BMI. Laboratory investigations included blood tests for FSH, LH, prolactin and AMH levels done for all women who participated in this study. <b>Results:</b> Age and BMI were comparable for PCOS cases and controls. The AMH levels in women with PCOS increased statistically with severity compared to controls, with the mean AMH level found to be 3.53 ng mL¹ in controls, whereas it ranged from 6.19 for mild cases to 7.49 for moderate cases to 12.83 for severe cases in PCOS cases. The AMH alone had the highest diagnostic sensitivity (78.6%) and specificity (97.6%) for PCOS at a cut-off of 5.82 ng mL¹. All study participants had a positive correlation between AMH and LH (R² = 0.391, p = 0.0031). <b>Conclusion:</b> The AMH levels were noticeably higher in PCOS patients compared to controls. The AMH could not accurately diagnose PCOS when used as an independent marker. The AMH levels did, however, have good diagnostic potential in combination with current Rotterdam criteria for PCOS diagnosis.

To ascertain the risk of progression to diabetes among Chinese women with PCOS.

Women with PCOS (n = 3978) were identified from the Hong Kong Diabetes Surveillance Database based on the ICD-9 code for PCOS diagnosis and women without PCOS served as controls (n = 39780), matched 1:10 by age.

The mean follow-up was 6.28 ± 4.20 and 6.95 ± 4.33 years in women with PCOS and controls, respectively. The crude incidence rate of diabetes was 14.25/1000 person-years in women with PCOS compared with 3.45 in controls. The crude hazard ratio of diabetes in women with PCOS was 4.23 (95 % CI: 3.73-4.80, p < 0.001). Further stratified by age group, the risk of developing diabetes decreased with increasing age but it remained significantly higher in women with PCOS across all age groups. It also suggested that the incidence rate of diabetes in women with PCOS aged 20-29 is highly comparable to that in healthy women aged ≥ 40. More than half of the incident diabetes captured during the follow-up in women with PCOS cohort were young-onset diabetes.

Women diagnosed with PCOS at a younger age have the highest relative risk of developing diabetes, suggesting frequent glycemic status screening is required to detect diabetes at an early stage.

Is there an association between post-occlusive reactive hyperaemia (PORH) and ovarian stimulation in women with normoandrogenaemic polycystic ovary syndrome (PCOS)?

Women eligible for IVF at an academic fertility centre were invited to join this prospective study. Microvascular endothelial function was measured as PORH by laser Doppler flowmetry (LDF) before and after ovarian stimulation. Metabolic characteristics, hormone profiles and biochemical markers were analysed.

Thirty-four normoandrogenaemic women with PCOS and 36 normoandrogenaemic women without PCOS were included. The PCOS group displayed higher C-reactive protein levels and insulin resistance (P = 0.048 and P = 0.025, respectively). No significant difference was found in microcirculatory function between the groups at baseline. After ovarian stimulation, PORH was enhanced in the control group (slope 7.1 ± 3.3 versus 9.7 ± 4.5; P = 0.007; peak flow 30.7 ± 16.3 versus 43.5 ± 17.3, P = 0.008; however, the PCOS group experienced a blunting response to supraphysiological hormone status (slope 8.2 ± 5.1 versus 7.2 ± 4.3, P = 0.212; peak flow, 38.8 ± 19.4 versus 37.0 ± 21.8, P = 0.895).

Impaired microcirculatory function could be found using a non-invasive LDF technique in normoandrogenaemic women with PCOS undergoing IVF, indicating early changes in vascular endothelial dysfunction. Future observational studies should clarify whether PORH measurement might help predict IVF prognosis or obstetric complications.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder in women of reproductive age. It presents with gynaecologic, metabolic, and psychologic manifestations. The dominant drivers of pathophysiology are hyperandrogenism and insulin resistance. Both conditions are related to cardiometabolic risk factors, such as obesity, hypertension, dyslipidaemia, hyperglycaemia, type 2 and gestational diabetes, nonalcoholic fatty liver disease and obstructive sleep apnoea. Women with PCOS of reproductive age consistently demonstrated an elevated risk of subclinical atherosclerosis, as indicated by different measurement methods, while findings for menopausal age groups exhibited mixed results. Translation of subclinical atherosclerosis into the increased incidence of peripheral arterial disease and major cardiovascular (CV) events is less clear. Although several expert groups have advised screening, the CV risk assessment and prevention of CV events are frequently underdiagnosed and overlooked aspects of the management of PCOS. A combination of lifestyle management and pharmacotherapy, including the promising new era of anti-obesity medicine, can lead to improvements in cardiometabolic health.

Dyslipidemia is an established risk factor for cardiovascular disease (CVD), which remains the leading cause of morbidity and mortality in women globally. The incidence of dyslipidemia increases over a woman's lifespan, with adverse changes around the time of menopause. Menopause, and the years leading up to the final menstrual period, is a time of estrogen fluctuation and ultimately estrogen deficiency, which has been associated with proatherogenic changes in the lipid profile. Independent of aging, menopausal status is associated with elevations in serum total cholesterol, LDL cholesterol, apolipoproteins, and triglycerides, and decreases in HDL cholesterol (HDL-C). Emerging research also suggests that after menopause there is a loss of functional HDL cardioprotective properties. Early initiation of menopausal hormone therapy (MHT) confers a favorable effect on lipid profile, though this does not translate into improved CVD outcomes and therefore guidelines do not indicate it for primary or secondary prevention of CVD. At the time of menopause, special consideration should be given to women with conditions more associated with CVD, including polycystic ovarian syndrome, premature menopause, early menopause, premature ovarian insufficiency, and familial hypercholesterolemia. Statins remain the mainstay of dyslipidemia therapy, though novel lipid-lowering agents are emerging. This review provides an overview of lipid alterations observed during the menopausal transition, summarizes the current evidence on the role of estrogen and progestogen on lipids, identifies special populations of women at especially high risk for lipid dysregulation at menopause, and describes approaches to the screening and treatment of midlife women.

Telomeres are DNA-protein complexes that protect chromosome ends from DNA damage and are surrogate biomarkers of cellular aging. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardiometabolic 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.

This is a population-based cohort study comprising women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (age 31, n = 190; age 46, n = 207) and referent women (age 31, n = 1054; age 46, n = 1324) with data on LTL.

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.

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).

This finding may suggest a difference in the 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.

Women with polycystic ovary syndrome (PCOS) have high circulating anti-Müllerian hormone (AMH) levels which is correlated with antral follicle count and polycystic ovarian morphology and negatively correlated with body mass index (BMI). Moreover, diet-induced weight loss in women with PCOS and overweight or obesity, reduce or normalize AMH-levels. There is, however, no previous study investigating the circulating AMH levels in women with severe obesity and how a structured diet-induced weight loss program affects circulating AMH levels in these women. Therefore, this study aims to investigate circulating AMH levels in a population of women with severe obesity (BMI ≥ 35 kg/m²) with and without PCOS, as diagnosed by the NIH-criteria, and to investigate the effect of a one-year weight loss program with a very low-energy diet (VLED) on circulating levels of AMH.

In a prospective cohort-study, were 246 women with severe obesity were screened for PCOS diagnosis with the NIH-criteria, circulating AMH and anthropometry were measured at baseline and after a 12-month weight loss intervention with very low-energy diet (VLED).

Mean BMI was 39.9 ± 4.7 (PCOS), 39.6 ± 4.3 (non-PCOS) P = 0.960. Circulating AMH was higher in women with PCOS (5.47 ± 4.89 µg/L) compared with non-PCOS (2.66 ± 3.71 µg/L) P < 0.001 and was positively correlated with circulating total testosterone in both groups. Next, we performed ROC-analyses, and show that circulating AMH could not discriminate women with PCOS and severe obesity from non-PCOS women with severe obesity. Finally, a one-year weight reduction program does not affect circulating AMH levels despite significant weight loss neither in women with PCOS, nor without PCOS and severe obesity.

Women with severe obesity and PCOS have elevated levels of circulating AMH compared to women without the syndrome. AMH-levels could not discriminate women with PCOS from non-PCOS because of low sensitivity and specificity. Significant weight loss was not associated with changes in circulating AMH levels, neither in women with, nor without PCOS and severe obesity. These results imply that in women with severe obesity, a greater weight loss may be needed to improve reproductive features, independent of PCOS diagnosis.

Clinical trial.gov: NCT01319162.

Polycystic ovary syndrome (PCOS) is a common hormonal, metabolic and reproductive disorder. Women with PCOS at reproductive age have increased risk and prevalence of prediabetes and diabetes and have multiple risk factors for cardiometabolic disease and other comorbidities such as obstructive sleep apnoea, endometrial cancer and mood disorders, which contribute to the overall health burden of the syndrome. However, little is known about the impact of PCOS on long-term health in ageing women. In this review, we aimed to give an updated overview regarding the long-term health outcomes of PCOS and their clinical implications in peri- and postmenopause. The PCOS phenotype ameliorates with ageing and limited available data suggest that there is no further deterioration in cardiometabolic profile in women with PCOS after menopause. Accordingly, the risk of cardiovascular disease in ageing women with PCOS seems to be no different from those without PCOS and lower than previously anticipated based on their risk during reproductive years. Regarding other comorbidities including sleep apnoea, mood disorders and endometrial cancer, it is difficult to determine the true risk in older women with PCOS due to the confounding factors and lack of long-term cohort studies. Large, prospective studies on community-based and well-phenotyped PCOS cohorts with extended follow-up into late menopause are needed to confirm these findings.

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.

This population-based follow-up study investigated the comorbidities, medication use, and healthcare services among women with polycystic ovary syndrome (PCOS) at age 46 years.

The study population derived from the Northern Finland Birth Cohort 1966 and consisted of women reporting oligo/amenorrhea and hirsutism at age 31 years and/or a PCOS diagnosis by age 46 years (n = 246) and controls without PCOS symptoms or diagnosis (n = 1573), referred to as non-PCOS women. The main outcome measures were self-reported data on symptoms, diagnosed diseases, and medication and healthcare service use at the age of 46 years.

Overall morbidity risk was increased by 35% (risk ratio [RR] 1.35, 95% confidence interval [CI] 1.16-1.57) and medication use by 27% [RR 1.27, 95% CI 1.08-1.50) compared with non-PCOS women, and the risk remained after adjusting for body mass index. Diagnoses with increased prevalence in women with PCOS were migraine, hypertension, tendinitis, osteoarthritis, fractures, and endometriosis. PCOS was also associated with autoimmune diseases and recurrent upper respiratory tract infections and symptoms. Interestingly, healthcare service use did not differ between the study groups after adjusting for body mass index.

Women with PCOS are burdened with multimorbidity and higher medication use, independent of body mass index.

The impact of low-dose spironolactone (LSPL), on polycystic ovarian syndrome (PCOS)- associated cardio-renal disorder is unknown. Therefore, the present study hypothesized that LSPL would ameliorate cardio-renal disorders in experimental PCOS animals. Eight-week-old Female Wistar rats were allotted into three groups. The control group received vehicle (distilled water; p.o.), LET-treated group designated as PCOS group received letrozole (1 mg/kg; p.o.), while PCOS+LSPL received letrozole and LSPL (0.25 mg/kg, p.o.). The treatment was done once daily for 21 days uninterrupted. The experimental PCOS rats were characterized with insulin resistance as well as, elevated testosterone and LH/FSH with a significant increase in cardiac and renal lipid profile, oxidative stress, inflammatory biomarkers (NF-κB and TNF-α), LDH and lactate content and decrease in cardiac and renal antioxidant system (GPX and GSH) compared with the control rats. There was also a significant increase in cardiac GGT but not renal GGT activity in PCOS animals. In addition, immunohistochemical assessment of cardiac and renal tissue showed significant expression of inflammasome and BAX in animals with PCOS. Nevertheless, these perturbations were attenuated following the administration of LSPL. Collectively, the present results suggests that LSPL attenuates PCOS-associated cardio-renal disorders by reduction of oxidative stress and BAX/Inflammasome expression.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting approximately 10%. PCOS is diagnosed by the presence of at least two of these three criteria: hyperandrogenemia, oligo- or anovulation, and polycystic ovaries. The most common type (80%) of PCOS includes hyperandrogenemia. PCOS is also characterized by obesity or overweight (in 80% of US women with PCOS), insulin resistance with elevated plasma insulin but not necessarily hyperglycemia, dyslipidemia, proteinuria, and elevated BP. Although elevated compared with age-matched controls, BP may not reach levels considered treatable according to the current clinical hypertension guidelines. However, it is well known that elevated BP, even modestly so, increases the risk of cardiovascular disease. We have developed a model of hyperandrogenemia in rodents that mimics the characteristics of PCOS in women, with increases in body weight, insulin resistance, dyslipidemia, andproteinuria and elevated BP. This review discusses potential mechanisms responsible for the elevated BP in the adult and aging PCOS rat model that may be extrapolated to women with PCOS.

To determine the prevalence of incidental findings (IFs) on coronary computed tomography (CCT) in women aged 45-55 years and previously diagnosed with reproductive disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) or preeclampsia (PE).

A total of 486 middle-aged women with PCOS (n = 101), POI (n = 97) or a history of PE (n = 288) underwent a CCT as part of a prior prospective study. IFs were categorized by their significance (minor, moderate and major). Follow-up information was collected from patients' records. To investigate the impact of different field of views (FOVs), a subset of scans was analyzed in full FOV and small FOV.

In 96/486 (19.8%) women, one or more IFs were detected, of which 54/486 (11.1%) were classified as moderate/major and 48/486 (9.9%) required follow-up. A moderate/major IF was detected in 16/101 (15.9%) women with PCOS, 13/97 (13.4%) women with POI and 25/288 (8.7%) women with a history of PE. In 78 women with an IF detected in the full FOV, the IF was still visible in 60 (76.9%) women in the small FOV. In the full FOV, 46 women required follow-up, but using the small FOV this was reduced to 30 women.

Using CCT as a cardiovascular disease screening tool in women with selected reproductive disorders increases the probability of detecting IFs that can cause anxiety and may generate extra costs, but can also reveal clinically relevant findings. Using a small FOV centered around the heart resulted in a lower prevalence of IFs and required less follow-up.

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?

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.

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.

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.

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.

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.

There was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches.

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.

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.

Prospero registration number: CRD42020165546.

Endocrine diseases may be associated with dyslipidaemia and may increase atherosclerotic cardiovascular disease (ASCVD) risk. This chapter describes changes in lipids and lipoproteins in diseases of the pituitary, thyroid, adrenal glands, ovaries, and testes, the mechanisms for these changes, ASCVD risk in these endocrine disorders, and whether treatment of the endocrine disorder improves the lipid profile and reduces ASCVD risk. Acromegaly, GH deficiency, Cushing syndrome, chronic glucocorticoid replacement, hypothyroidism, PCOS and male hypogonadism can increase LDL-C and/or TG. Marked reductions in LDL-C are associated with hyperthyroidism, and extremely low HDL-C levels with testosterone and/or other anabolic steroid abuse. Acromegaly, GH deficiency, Cushing syndrome, and chronic glucocorticoid replacement are associated with increased ASCVD risk. Treatment of acromegaly, GH deficiency, hypothyroidism, Cushing syndrome, and testosterone deficiency reduce LDL-C, although statin therapy may still be needed. Effects on ASCVD are not known.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age and is hallmarked by hyperandrogenism, oligo-ovulation, and polycystic ovarian morphology. Polycystic ovary syndrome, particularly the hyperandrogenism phenotype, is associated with several cardiometabolic abnormalities, including obesity, dyslipidemia, elevated blood pressure, and prediabetes or type 2 diabetes. Many, but not all, studies have suggested that PCOS is associated with increased risk of cardiovascular disease (CVD), including coronary heart disease and stroke, independent of body mass index and traditional risk factors. Interpretation of the data from these observational studies is limited by the varying definitions and ascertainment of PCOS and CVD across studies. Recent Mendelian randomization studies have challenged the causality of PCOS with coronary heart disease and stroke. Future longitudinal studies with clearly defined PCOS criteria and newer genetic methodologies may help to determine association and causality. Nevertheless, CVD risk screening remains critical in this patient population, as improvements in metabolic profile and reduction in CVD risk are achievable with a combination of lifestyle management and pharmacotherapy. Statin therapy should be implemented in women with PCOS who have elevated atherosclerotic CVD risk. If CVD risk is uncertain, measurement of subclinical atherosclerosis (carotid plaque or coronary artery calcium) may be a useful tool to guide shared decision-making about initiation of statin therapy. Other medications, such as metformin and glucagon-like peptide-1 receptor agonists, also may be useful in reducing CVD risk in insulin-resistant populations. Additional research is needed to determine the best pathways to mitigate PCOS-associated CVD risk.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Apart from the reproductive problems, PCOS is also associated with metabolic disturbances, and therefore, it also affects adolescents and postmenopausal women with PCOS as well as their offspring and other first-degree relatives. Adolescents with PCOS show unfavorable cardiometabolic biomarkers more often than controls, such as overweight/obesity and hyperandrogenism, and studies also suggest an unfavorable lipid profile. During reproductive age, women with PCOS develop additional cardiometabolic biomarkers, such as hypertension, insulin resistance, and metabolic syndrome. Growing evidence also supports the important role of inflammatory cytokines in cardiovascular health in these women. During menopausal transition, some PCOS characteristics ameliorate, whereas other biomarkers increase, such as body mass index, insulin resistance, type 2 diabetes, and hypertension. Offspring of women with PCOS have a lower birth weight and a higher body mass index later in life than controls. In addition, fathers, mothers, and siblings of women with PCOS show unfavorable cardiometabolic biomarkers. Therefore, cardiovascular screening and follow-up of women with PCOS and their offspring and siblings are of utmost importance.

The existing data regarding the impact of Polycystic Ovary Syndrome (PCOS) on the risk of developing cardiovascular disease (CVD) are conflicting.

To explore the effect of PCOS status on the occurrence of silent coronary artery disease (CAD)/CVD.

A total of 1591 women without CVD at baseline, aged 18-45 years, including 356 PCOS patients (defined by the Rotterdam criteria) and 1235 eumenorrheic non-hirsute women without polycystic ovarian morphology (controls), were selected from the Tehran Lipid and Glucose Study (TLGS). The median follow-up was 15.4 years, and most participants were in their late reproductive years at the end of the study. Silent CAD and CVD outcomes in PCOS and control groups were compared according to the multivariable-adjusted hazard ratios (HRs) and cumulative hazard functions.

There was no difference in CVD risk factors between the PCOS and control groups. After controlling for confounders, PCOS status did not increase the risk of silent CAD (HR: 0.96, 95% CI 0.86-1.08). Regardless of PCOS status, women with a history of silent CAD showed 2.25 times higher CVD events than those without this history (95% CI 1.63-3.10). PCOS status reduced the CVD incidence by 42%, independently of silent CAD or traditional risk factors (HR: 0.58, 95% CI 0.35-0.98).

Whereas silent CAD, regardless of PCOS, accelerated CVD, PCOS preserved it, most likely due to a combination of protective factors, including the endocrine pattern in the late reproductive period, environmental/social elements, and recruiting additional counseling and lifestyle modifications.

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.

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.

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.

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.

Despite the clear evidence of increased cardiovascular disease (CVD) risk factors, the long-term effect on CVD and mortality is still uncertain in women with PCOS, especially in the elderly. Studies in elderly women with PCOS are lacking. The objective was to study morbidity/mortality in PCOS women compared with a reference group up to a mean age above 80 years.

A well-defined cohort of women with PCOS, examined in 1987 and 2008, was re-examined 32 years later in 2019 (age range 72-91 years), in parallel with an age-matched reference group. For deceased women register data was used, for women alive interviews were done, and medical records studied. Blood pressure and blood tests were analyzed. Morbidity and mortality data was available in 35/36 women with PCOS, and in 99/118 women in the reference group.

At mean age 81 years there was no difference in all-cause mortality (HR 1.1, ns), CVD-related mortality (HR 1.7, ns), all CVD (HR 1.2, ns), hypertension (HR 1.8, ns), type 2 diabetes (HR 1.7, ns), in levels of blood lipids, glucose, insulin or thyroid hormones. Comparing baseline data from the deceased and living women with PCOS, no differences were found regarding age, menopausal age, BMI, HOMA-IR, FAI, total testosterone or SHBG. However, deceased women with PCOS had a higher WHR (0.87 vs. 0.80; p-value < 0.01) at baseline.

No evidence of increased all-cause mortality or CVD was found in women with PCOS. The elevated testosterone levels and CVD risk profile in PCOS present during perimenopause do not seem to be associated with increased CVD morbidity/mortality risk later in life.