Polycystic ovary syndrome and impact on health

Polycystic ovary syndrome (PCOS) is a multifactorial, heterogeneous, complex genetic, endocrine and metabolic disorder, diagnostically characterized by chronic anovulation, polycystic ovaries and biochemical and clinical manifestations of hyperandrogenism. It has a tremendous negative impact on the physiology and metabolism of the body as it may evolve into a metabolic syndrome with insulin resistance, hyperinsulinemia, abdominal obesity, hypertension and dyslipidemia presenting as frequent metabolic traits and culminating in serious long-term consequences, such as type 2 diabetes mellitus, endometrial hyperplasia and cardiovascular disease. The key endocrine abnormalities include dysregulation of the gonadotropin-releasing hormone (GnRH) pulse generator to feedback inhibition by ovarian steroids, resulting in luteinizing hormone (LH) hypersecretion, and decreased follicle-stimulating hormone (FSH), and ovarian stromal–thecal hyperactivity, resulting in ovarian hyperandrogenism, all of which may lead to significant biochemical, reproductive and metabolic dysfunction. Though it is detected in approximately 5–10% of women of reproductive age, recent evidence from experimental observations in animals, buttressed by human studies, suggest a deep-rooted developmental origin of PCOS, the pathophysiology of which progresses from infancy to adulthood. In utero fetal programming or dysregulation of the hypothalamic–pituitary–gonadotropic axis at crucial developmental stages, mediated by the interaction of genetically determined hyperandrogenism and environmental factors (obesity), may have a significant role in the development of the final expression of the PCOS phenotype and its long-term consequences, the symptoms of which may vary throughout lifespan, largely influenced by obesity, metabolic alterations and ethnicity. Several candidate genes involved in steroid hormone biosynthesis and metabolism, action of gonadotropins and gonadal hormones, obesity and energy regulation and insulin secretion and action, in addition to many others, have been implicated in the pathogenesis of the syndrome, suggesting a genetic basis for PCOS. Though several pharmacological therapies are available to alleviate the symptoms of PCOS and components of the associated metabolic syndrome, lifestyle modifications, including diet and exercise, have been proved most effective and should be employed as a first line intervention, and particularly so, since obesity has a central role in the pathogenesis of the disease. Active interventions to diagnose and treat the disorder from childhood before it is manifested in adolescence and imprinted in adulthood, should be the goal in combating PCOS and its related disorders