Beyond Monotherapy: Targeting the Triad of Insulin Resistance, Hyperandrogenism and Obesity in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age group. It is a heterogeneous condition with multifactorial etiology and polygenic inheritance. Most prevalent current management of PCOS involves oral contraceptive pills (OCPs) with/without antiandrogens along with lifestyle modification. Given the multifaceted pathophysiology of PCOS, addressing it with a single pharmacologic agent makes long-term management difficult. The comprehensive management of PCOS must target the clinical symptomatology as well as underlying pathophysiologic mechanisms. Obesity, which is commonly observed in PCOS, contributes significantly in the pathophysiology of PCOS by exacerbating insulin resistance (IR) and hyperandrogenism. Women with Obesity and PCOS have poorer metabolic and reproductive outcomes than nonobese women. Although OCPs are widely used as first-line pharmacologic agents, they may worsen metabolic function and have multiple adverse effects and contraindications. Metabolic dysfunction is more prevalent in women with obesity and PCOS due to the additive effect of obesity and PCOS. Hence, there is an urgent need of a multipronged approach that targets both the pathophysiology and symptomatology in women with obesity and PCOS. Although combination therapies for management of PCOS have been explored in the past, an integrated approach addressing all 3 components of obese PCOS together-namely IR, hyperandrogenism, and obesity remains underutilized. A therapeutic strategy using a combination of insulin sensitizers for IR, antiandrogens for hyperandrogenism, and antiobesity medications for weight management, along with lifestyle modification offers a more holistic approach. Such a regimen is expected to improve both metabolic and reproductive outcomes in women with obesity and PCOS while avoiding the adverse effects of hormonal therapy.