Androgens and Cardiovascular Risk Factors in Polycystic Ovary Syndrome

*Licy L. Yanes Cardozo, Alexandra M. Huffman, Jacob E. Pruett and Damian G. Romero*

## **Abstract**

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Clinical or biochemical signs of androgen excess is a cardinal feature of the syndrome and are present in approximately 80% of women with PCOS. Increased blood pressure and insulin resistance, two major cardiovascular risk factors, are frequently present in women with PCOS. This chapter aims to highlight the fundamental role of androgens in mediating the increased blood pressure and insulin resistance in women with PCOS. This chapter is also a call for action to develop new pharmacological therapies that target the androgen synthesis and androgen receptor activation dysregulation present in women with PCOS. These novel therapies will allow to prevent or mitigate the excess androgenmediated cardiovascular risk factors that affect women with PCOS.

**Keywords:** polycystic ovary syndrome, androgens, androgen receptor, blood pressure, insulin resistance

#### **1. Introduction**

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder and cause of androgen excess in reproductive-age women [1, 2]. The etiology of the syndrome is unknown, and the pathophysiological characteristics are complex. There are three different sets of diagnostic criteria available to diagnose PCOS; the Rotterdam criteria is the most commonly used. The key difference among those three criteria is that hyperandrogenism is considered an essential component of the syndrome for the Androgen Excess Society guidelines [3] and National Institutes of Health (NIH) [4], but not for the Rotterdam criteria [5]. More recently, the Rotterdam criteria for PCOS diagnosis were endorsed by the NIH at an NIHsponsored workshop [6] as well as by the International evidence-based guideline for the assessment and management of PCOS [7]. Insulin resistance (IR) is frequently present in lean and obese women with PCOS, but it is not included in the diagnostic criteria. Women with PCOS may seek medical care due to a broad range of clinical manifestations such as infertility, menstrual dysfunction, excessive hair growth or hirsutism, alopecia, or acne. More recently, it became clear that the cardiometabolic risk factors, such as IR, increases in blood pressure (BP), and obesity affect a high percentage of women with PCOS compared to normal cycling women [8–11].

Importantly, in women with PCOS, plasma levels of androgens positively correlate with BP and IR. Whether and how androgen excess causes increased BP and IR in women with PCOS is unknown. Unfortunately, limited effective evidence-based therapeutic agents are available to treat those cardiovascular risk factors in PCOS patients. Furthermore, the use of antiandrogens in PCOS is often only recommended to manage the dermatological manifestations of the syndrome, but neither the IR nor increases in BP [12]. This chapter aims to highlight the fundamental role of androgens in mediating increases in BP and IR in women with PCOS and the lack of therapeutic options to ameliorate the hyperandrogenism and cardiometabolic complications in these patients.
