Polycystic Ovary Syndrome in the Pediatric Population

Abstract

Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism and disordered gonadotropin secretion, often associated with insulin resistance. The syndrome, which modulates both hormonal and metabolic processes, is the most common endocrinopathy in reproductive-age women and increases a woman's risk of infertility, endometrial pathology, and cardiometabolic disease. As it is currently defined, PCOS most likely encompasses several distinct diseases with similar clinical phenotypes but different underlying pathophysiological processes. However, hyperandrogenism remains the syndrome's clinical hallmark. The clinical manifestations of PCOS often emerge during childhood or in the peripubertal years, suggesting that the syndrome is influenced by fetal programming and/or early postnatal events. However, given that the full clinical spectrum of PCOS does not typically appear until puberty, a ''two-hit'' hypothesis has been proposed: (1) a girl develops hyperandrogenism via one or more of many different potential mechanisms; (2) the preexisting hyperandrogenism subsequently disturbs the hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction and sustained hyperandrogenism. No consensus guidelines exist regarding the diagnosis and management of PCOS in the pediatric population; however, because the syndrome is a diagnosis of exclusion, the clinical evaluation of girls suspected of having PCOS is aimed at excluding other causes of androgen excess and menstrual dysfunction. For the syndrome's management, emphasis is placed on lifestyle and symptomdirected treatment.

Development of Obesity and Polycystic Ovary Syndrome in Adolescents

“…It defined PCOS as a syndrome of ovarian dysfunction, diagnosed when fulfilling two out of the three following criteria: (1) menstrual dysfunction/OAV; (2) enlarged polycystic ovaries (on ultrasonography); (3) clinical and/or biochemical HA. Additionally, however, other sets of criteria have been proposed [14]. These criteria, listed in table 1 differ in terms of which and how many conditions are necessary for a diagnosis.…”

“…Of particular interest are those related to the degree of IR, as IR seems instrumental in the codevelopment of PCOS and T2DM in obese adolescent girls [11]. Another factor of importance is HA as it exacerbates physiological changes of androgens during puberty, and one effect may be the initiation of precocious pubarche in girls which in turn, is a risk factor for PCOS [14]. Visceral fat also plays an independent role, and it is thought to exacerbate these hormonal alterations in adolescent girls [34].…”

Prenatal androgen excess programs metabolic derangements in pubertal female rats

“…Women with PCOS do not typically have structural abnormalities of insulin receptors (IRs), fewer IRs, or altered insulin binding affinity. Therefore, a post-receptor mechanism in adolescents with PCOS is most likely responsible for insulin resistance (Bremer 2010). Defects in the IR substrate (IRS)-AKT (also called protein kinase B (PKB)) pathway, which plays a key role in the regulation of glycogen synthesis, gluconeogenesis, and glucose transport by insulin, have been found in T2DM and PCOS, suggesting that a defective IRS-AKT pathway underlies the clinical development of insulin resistance (Corbould 2008).…”

Metabolic Syndrome: From Human Organ Disease to Fetal Programming

“…PCOS pathogenesis is multifactorial, and some evidence suggests that it is influenced by intrauterine exposure to excessive androgens [130]. It impairs the Hypothalamic-Pituitary-Ovarian (HPO) and hypothalamic-pituitary adrenal (HPA) axes, favoring the PCOS phenotype, which includes IR, hyperandrogenism, excessive luteinizing hormone secretion and reduced ovulation [131][132][133].…”

“…It impairs the Hypothalamic-Pituitary-Ovarian (HPO) and hypothalamic-pituitary adrenal (HPA) axes, favoring the PCOS phenotype, which includes IR, hyperandrogenism, excessive luteinizing hormone secretion and reduced ovulation [131][132][133]. Likewise, postnatal factors are also implicated in this complex pathogenesis: the association between low birth weight and rapid catch-up growth, premature menarche and sustained augmented visceral fat pad, the main predictors of PCOS in young girls [130,134].…”