PCOS BMR CALCULATOR SERIES
After a series of enzymatic reactions, cholesterol is converted into dehydroepiandrosterone (DHEA) and androstenedione. Androgens are produced in the ovary and adrenal gland from a common precursor, cholesterol. It is estimated that more than 80% of women who exhibit signs or symptoms of hyperandrogenism, including hirsutism, acne or alopecia, have PCOS. Hyperandrogenemia is considered the main clinical hallmark of PCOS. Finally, a brief recap is provided on the current therapeutic strategies for managing the metabolic complications of PCOS, which are urgently necessary for more effective treatment options, in particular subsets of PCOS patients. In addition, data from other species (for example, sheep and non-human primates) have been also included when relevant. Special emphasis was placed on discussing findings from studies of various female rodent models of hyperandrogenism generated by exposures to different types of androgens at various doses and administration windows, which resulted in a multiplicity of PCOS-like symptoms resembling the heterogenous clinical presentation of the syndrome. This study reviews the current literature to provide an overview of the main pathogenic mechanisms that may underlie metabolic dysregulation commonly linked to PCOS, with particular attention to the potential molecular mechanisms responsible for the metabolic impact of androgen excess in selective tissues. However, a better understanding of the molecular mechanisms underlying the metabolic actions of androgens in PCOS is needed. Androgen excess has a deleterious impact on metabolic homeostasis in women with PCOS, acting on different metabolic tissues such as the adipose tissue, liver, muscle, and pancreas as well as on the brain. Although many aspects of its pathophysiology remain obscure, it is widely accepted that hyperandrogenism plays a fundamental role in the development of most of the reproductive and metabolic perturbations associated with PCOS. Several lines of evidence suggest that developmental, environmental, genetic, and epigenetic mechanisms are involved in the etiology of this endocrine disorder. The pathophysiological mechanisms of PCOS are complex and not fully understood. Importantly, the prevalence of these metabolic comorbidities is high in women with this disorder, and the concurrence of overweight or obesity and PCOS exacerbates not only metabolic complications, but also reproductive derangements associated with this endocrinopathy. Hyperinsulinemia plays a prominent role in the development of some phenotypic features of PCOS and, together with β cell dysfunction, increases the risk of developing other metabolic abnormalities such as type 2 diabetes (T2D), hypertension, dyslipidemia, and cardiovascular diseases. Of note, IR and hyperinsulinemia are metabolic traits that are also present in most lean women with PCOS. A large proportion of women with PCOS are obese or overweight and exhibit IR with associated compensatory hyperinsulinemia.
PCOS is closely linked to metabolic disorders such as obesity and insulin resistance (IR). However, the deleterious impact of this pathology is not confined to reproductive function, and metabolic function is also frequently compromised. PCOS is considered the leading cause of anovulatory infertility and is therefore clinically associated with subfertility or infertility. According to the Rotterdam criteria, the most widely used for the clinical diagnosis of PCOS is defined by at least two of the three aforementioned clinical features. Currently, there are several diagnostic criteria for PCOS that utilize different combinations of these clinical traits. PCOS is a complex and heterogeneous endocrinopathy characterized by a constellation of symptoms and clinical features, including hyperandrogenism (clinical or biochemical), ovarian dysfunction (menstrual irregularities), and polycystic ovarian morphology. Globally, the incidence of this syndrome varies, ranging from 6% to 20% depending on the diagnostic criteria applied, with higher prevalence in overweight or obese women and in specific ethnic groups. Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder among premenopausal women.
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