Obesity and Polycystic Ovary Syndrome

Abstract

The core pathophysiology of polycystic ovary syndrome involves an overproduction of androgens primarily originating from ovarian thecal cells. Two major external triggers promote androgen overproduction in the ovaries: the increased secretion of luteinizing hormone, a consequence of aberrant hypothalamic gonadotropin-releasing hormone secretion dynamics, and compensatory hyperinsulinemia resulting from insulin resistance. Obesity interacts with polycystic ovary syndrome in multiple ways, but a major role of obesity in its pathophysiology is the exacerbation of insulin resistance. Additionally, obesity contributes to polycystic ovary syndrome by facilitating the conversion of precursor hormones to testosterone within adipose cells. Moreover, obesity can lead to relative hyperandrogenemia, which is marked by lower levels of sex hormone binding globulin and increased availability of free testosterone to target tissues. Also, obesity affects the secretion of gonadotropins, resulting in heightened luteinizing hormone secretion or increased sensitivity of thecal cells to luteinizing hormone. Obesity-related insulin resistance might be amplified by alterations in adipokine and inflammatory cytokine production. Ultimately, obesity and polycystic ovary syndrome might share a common genetic predisposition. The cornerstone of managing polycystic ovary syndrome is to address individual symptoms such as hyperandrogenism (hirsutism, acne, and female type boldness), menstrual irregularities, and infertility stemming from anovulation. However, obesity is integral to the pathophysiology of polycystic ovary syndrome and exacerbates all of its features. Therefore, lifestyle modifications aimed at weight reduction should be the primary strategy in overweight or obese women with polycystic ovary syndrome.

Keywords: Anovulation; Insulin resistance; Obesity; Polycystic ovary syndrome.

Figure 1

Pathophysiology of polycystic ovary syndrome (PCOS). The fundamental pathophysiology of PCOS encompasses excessive production of androgens primarily from the ovaries (and, to a lesser extent, the adrenal glands). There are two major external factors driving ovarian androgen overproduction: one is the elevated secretion of luteinizing hormone (LH) via the hypothalamic-pituitary axis, and the other is increased insulin levels stemming from insulin resistance. Obesity significantly contributes to PCOS pathophysiology primarily by worsening insulin resistance, but it also plays a role by converting precursor androgens to testosterone within adipose tissues directly. Furthermore, obesity influences gonadotropin release, leading to a rise in LH secretion or enhancing the sensitivity of thecal cells to LH stimulation. Obesity-induced insulin resistance may be further exacerbated by variation in adipokine and inflammatory cytokine levels. Lastly, obesity and PCOS may share an underlying genetic predisposition. GnRH, gonadotropin-releasing hormone.