Origins Of Polycystic Ovary Syndrome Research Articles

Epigenetic abnormality: A possible mechanism underlying the fetal origin of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is one of the most common, yet heterogeneous and complex, endocrine disorders in women of reproductive age. Although the aetiology of PCOS remains uncertain, emerging evidence has indicated that exposure of the female fetus to the hyperandrogenism milieu in utero may result in PCOS phenotype after birth. Such a phenomenon has been formulated as the fetal origin of PCOS, which intends to give a possible explanation for PCOS aetiology. Given that the epigenetic modifications are usually involved in the development and inheritance of many adult diseases with fetal origin, we propose a hypothesis here referred to as "epigenetic abnormality underlying the fetal origin of PCOS". It states that in utero hyperandrogenism exposure may disturb the epigenetic reprogramming in fetal reproductive tissue, thereby resulting in postnatal POCS phenotype in women of reproductive age. Meanwhile, the incomplete erasure of such epigenetic abnormality in germ cells after fertilization may promote the transgenerational inherence of POCS. Thus, this epigenetic abnormality hypothesis has established a novel mechanism for PCOS development and inheritance. If verified, our hypothesis would open new avenues for the possible intervention at the critical period of prenatal life to prevent PCOS development and inheritance in adult women. Moreover, analysis of the epigenetic phenotypes and identification of specific epigenetic changes may help develop new tools for monitoring fetal development under an in utero hyperandrogenism environment.

Early origins of polycystic ovary syndrome

The prenatally androgenised female rhesus monkey has become a model for polycystic ovary syndrome (PCOS) in women, with early prenatal androgenisation entraining a permanent PCOS-like phenotype characterised by luteinising hormone (LH) hypersecretion due to reduced hypothalamic sensitivity to steroid negative feedback and relative insulin excess associated with increased abdominal adiposity. These combined reproductive and metabolic abnormalities occur in combination with ovarian hyperandrogenism and follicular arrest in adulthood, and with premature follicle differentiation and impaired embryo development during gonadotrophin therapy for in vitro fertilization (IVF). The ability of prenatal androgen excess in fetal rhesus monkeys to entrain multiple organ systems in utero provides evidence that the hormonal environment of intrauterine life programmes target tissue differentiation, raising the possibility that hyperandrogenism in human fetal development promotes PCOS in adulthood. This hypothesis developed in prenatally androgenised female rhesus monkeys, however, also must include data from clinical studies of PCOS to clarify the homology between human and non-human primates in intrafollicular steroidogenesis and its impact on oocyte developmental competency. By doing so, future studies promise to develop new clinical strategies that will lead to improved pregnancy outcome and reduced pregnancy loss in women with disorders of insulin action, including PCOS, obesity and diabetes mellitus.

Developmental origin of polycystic ovary syndrome - a hypothesis.

Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is a major cause of anovulation and consequent subfertility. It is also associated with a metabolic disturbance, characterized by hyperinsulinaemia and insulin resistance that carries an increased risk of type 2 diabetes in later life. Despite its prevalence little is known about its aetiology, but there is increasing evidence for an important genetic involvement. On the basis of experimental observations in the prenatally androgenized sheep and rhesus monkey, and supported by data from human studies, we propose that the clinical and biochemical features of PCOS can arise as a consequence of genetically determined hypersecretion of androgens by the ovary during, or very likely long before, puberty. The resulting hyperandrogenism results in 'programming' of the hypothalamic-pituitary unit to favour excess LH secretion, and encourages preferential abdominal adiposity that predisposes to insulin resistance. The severity of hyperinsulinaemia and insulin resistance (which has a profound influence on the phenotype of PCOS) is further influenced by both genetic factors (such as polymorphism in the insulin gene regulatory region) and environmental factors, notably obesity. This hypothesis therefore suggests a unifying, 'linear' model to explain the aetiology of the heterogeneous phenotype.

Insulin sensitizers and antiandrogens in the treatment of polycystic ovary syndrome.

The heterogeneous origin of polycystic ovary syndrome (PCOS) has been demonstrated by several studies. Abnormalities in steroidogenesis and metabolism are present, but the exact link between these two pathologic features remains to be clarified. In clinical practice, more than one therapeutic approach for the treatment of this syndrome has been proposed over the last few decades. Because hyperandrogenism and hyperinsulinemia contribute to a different degree to the phenotype of PCOS, therapeutic efforts have focused on agents that could treat or modify the clinical manifestations of these disorders. Antiandrogens as a sole treatment or combined with oral contraceptives are considered the treatment of choice for the manifestations of hyperandrogenemia, but there is no agreement about their efficacy on the metabolic sequelae of PCOS (insulin resistance, hyperinsulinemia, dislipidemia). Furthermore, the improvement of insulin sensitivity by insulin sensitizers may be of therapeutic value directly and/or indirectly in the management of clinical manifestations of hyperinsulinemia and hyperandrogenemia.

Psychoneuroendocrine aspects of polycystic ovary syndrome

It has been suggested that the psychological aspects of polycystic ovary syndrome (PCOS) may be involved in its pathogenesis. In order to investigate the possible role of personality factors in the origin of PCOS, 21 patients complaining of the syndrome were enrolled in the study. Beside their clinical and hormonal parameters, the psychological profiles of the patients were evaluated by administration of Minnesota multiphasic personality inventory (MMPI) and State-Trait anxiety inventory (STAI) psychometric tests. Patients with PCOS showed significantly higher depression and anxiety scores than controls and 52.4% of them scored above the upper limit of the normal D scale (depression) of MMPI. Probably because of psychological background, women with PCOS showed different psychometric assessments, allowing the identification of two subgroups of patients, those with and those without increased levels of depression and anxiety. No correlation was found between psychological disturbances, on one side, and clin...