Role of hormonal and inflammatory alterations in obesity-related reproductive dysfunction at the level of the hypothalamic-pituitary-ovarian axis

Background: Besides being a risk factor for multiple metabolic disorders, obesity could affect female reproduction. While increased adiposity is associated with hormonal changes that could disrupt the function of the hypothalamus and the pituitary, compelling data suggest that obesity-related hormonal and inflammatory changes could directly impact ovarian function. Objective: To review the available data related to the mechanisms by which obesity, and its associated hormonal and inflammatory changes, could affect the female reproductive function with a focus on the hypothalamic-pituitaryovarian (HPO) axis. Methods: PubMed database search for publications in English language until October 2017 pertaining to obesity and female reproductive function was performed. Results: The obesity-related changes in hormone levels, in particular leptin, adiponectin, ghrelin, neuropeptide Y and agouti-related protein, are associated with reproductive dysfunction at both the hypothalamic-pituitary and the ovarian levels. The pro-inflammatory molecules advanced glycation end products (AGEs) and monocyte chemotactic protein-1 (MCP-1) are emerging as relatively new players in the pathophysiology of obesity-related ovarian dysfunction. Conclusion: There is an intricate crosstalk between the adipose tissue and the inflammatory system with the HPO axis function. Understanding the mechanisms behind this crosstalk could lead to potential therapies for the common obesity-related reproductive dysfunction.