Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine-disrupting chemical exposure, and the influence of lifestyle factors such as poor-quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

Polycystic ovary syndrome (PCOS) is a common metabolic–endocrine disorder affecting women of reproductive age, and insulin resistance (IR) is a key pathophysiological feature. Current medical education and clinical practice emphasize glucose-centric approaches in PCOS management, and IR testing is often overlooked due to limited emphasis in current clinical guidelines or the lack of standardized protocols. Additionally, the glucose-focused paradigm has been the standard of care for decades. However, this approach has led to delayed diagnosis of progressive metabolic and reproductive consequences, leaving many patients underdiagnosed and undertreated. Therefore, we propose a paradigm shift towards an insulin-centric model for PCOS management. This new approach aims to diagnose IR at an earlier stage, enabling the timely implementation of effective lifestyle and treatment strategies. By focusing on IR, clinicians can potentially limit the progression of PCOS-related reproductive and metabolic diseases. The insulin-centric model is a novel approach that involves comprehensive IR screening, dynamic insulin testing, personalized lifestyle and insulin-sensitizing interventions, and regular monitoring of insulin and glycemic parameters. This model could improve patient outcomes by facilitating early diagnosis of metabolic dysfunction and reducing the incidence of subsequent chronic disease. Furthermore, this model has broader implications, potentially transforming treatment approaches for various chronic diseases beyond PCOS.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labor, and pre-eclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This narrative synthesis summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidence-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early-pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

Testosterone and cardiovascular health: Questions and controversies. DVT, deep vein thrombosis; FDA, Food and Drug Administration; T, testosterone; TGM, transgender men; TT, testosterone therapy; VTE, venous thromboembolism.

The debate over the safety and benefit of hormone replacement therapy (HRT) in postmenopausal women for primary prevention of cardiovascular disease (CVD) has been ongoing for the past several decades. Observational trials in the 1980s suggested a benefit of HRT for primary CVD prevention. However, randomized controlled trials in the 1990s suggested potential harm. Because of these discrepancies, recommendations from authorities on the usage of postmenopausal HRT have fluctuated. Many believed that the timing of HRT initiation relative to the onset of menopause, also known as the “timing hypothesis,” was the factor that could explain the differences among these studies. Some recent investigations have concluded that HRT initiated in postmenopausal women near the onset of menopause confers a cardioprotective benefit, while others simply showed that HRT does not cause harm. Research has expanded to evaluate alternative doses, preparations, routes, and formulations, including selective estrogen receptor modulators, to demonstrate their suitability for this purpose. This article is a review of the major research studies of HRT in postmenopausal women with respect to its safety and efficacy for the primary prevention of CVD.