madman
Super Moderator
Recent advances in emerging PCOS therapies (2023)
Kelly A. Glendining and Rebecca E. Campbell
Abstract
Polycystic ovary syndrome is a prevalent endocrinopathy involving androgen excess and anovulatory infertility. The disorder is also associated with many comorbidities such as obesity and hyperinsulinemia, and an increased risk of cardiovascular complications. Reproductive, endocrine, and metabolic symptoms are highly variable, with heterogenous phenotypes adding complexity to the clinical management of symptoms. This review highlights recent findings regarding emerging therapies for treating polycystic ovary syndrome, including i) pharmacological agents to target androgen excess, ii) modulation of kisspeptin signaling to target central neuroendocrine dysregulation, and iii) novel insulin sensitizers to combat peripheral metabolic dysfunction.
Introduction
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that is a leading cause of infertility in reproductive-aged women [1,2], and with an increasing incidence globally [3]. The most widely accepted guidelines for a clinical diagnosis of PCOS require the presence of a minimum of two out of three principal features: physical or biochemical signs of androgen excess, ovulatory dysfunction, and polycystic ovarian morphology [4]. However, a range of comorbidities is also associated with the disorder, including obesity, insulin resistance, type 2 diabetes, and cardiovascular conditions [5-8], contributing to heterogeneous phenotypes. Currently, there is no cure for PCOS, with therapies centered on the management of symptoms, and/or assisted fertility. This review will provide a brief summary of PCOS pathophysiology, and current standard treatments for PCOS, followed by an overview of recent findings regarding novel and emerging therapeutic strategies in PCOS management. In particular, focussing on pharmacological targeting of androgen excess, central neuroendocrine dysfunction, and peripheral metabolic pathophysiology.
*Pathophysiology of PCOS
*Current recommended treatments for PCOS
*Novel and emerging strategies for treatment of PCOS
*New treatments targeting androgen excess
*Clinical targeting of neuroendocrine dysfunction
-Modulation of kisspeptin
-Modulation of neurokinin B
-Modulation of dynorphin
*Treatments targeting insulin resistance
-Humanin
-Sodium glucose co-transporters (SGLT1, SGLT2)
-Incretin mimetics
Conclusion
There are a number of promising new therapies for PCOS emerging, which comprise a range of pharmacological strategies to target androgen excess, central neuroendocrine dysfunction, and/or metabolic pathophysiology (see Table 1). While there are no current AR antagonists approved for the treatment of PCOS, there is growing interest in the potential of therapeutic modulation of SHBG to manage hyperandrogenism. Recent evidence from clinical studies indicates that modulators of the KNDy neuronal network that target the central neuroendocrine pathophysiology of PCOS may also be incredibly useful therapeutic tools. Similarly, humanin, SGLT2 inhibitors, and incretin mimetics show promise in mitigating metabolic dysregulation in PCOS. These emerging PCOS therapies have the potential to improve patient outcomes in the future, beyond currently available strategies. However, further clinical investigations are needed to verify their efficacy and safety, particularly over the long term, and across PCOS phenotypes.
Kelly A. Glendining and Rebecca E. Campbell
Abstract
Polycystic ovary syndrome is a prevalent endocrinopathy involving androgen excess and anovulatory infertility. The disorder is also associated with many comorbidities such as obesity and hyperinsulinemia, and an increased risk of cardiovascular complications. Reproductive, endocrine, and metabolic symptoms are highly variable, with heterogenous phenotypes adding complexity to the clinical management of symptoms. This review highlights recent findings regarding emerging therapies for treating polycystic ovary syndrome, including i) pharmacological agents to target androgen excess, ii) modulation of kisspeptin signaling to target central neuroendocrine dysregulation, and iii) novel insulin sensitizers to combat peripheral metabolic dysfunction.
Introduction
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that is a leading cause of infertility in reproductive-aged women [1,2], and with an increasing incidence globally [3]. The most widely accepted guidelines for a clinical diagnosis of PCOS require the presence of a minimum of two out of three principal features: physical or biochemical signs of androgen excess, ovulatory dysfunction, and polycystic ovarian morphology [4]. However, a range of comorbidities is also associated with the disorder, including obesity, insulin resistance, type 2 diabetes, and cardiovascular conditions [5-8], contributing to heterogeneous phenotypes. Currently, there is no cure for PCOS, with therapies centered on the management of symptoms, and/or assisted fertility. This review will provide a brief summary of PCOS pathophysiology, and current standard treatments for PCOS, followed by an overview of recent findings regarding novel and emerging therapeutic strategies in PCOS management. In particular, focussing on pharmacological targeting of androgen excess, central neuroendocrine dysfunction, and peripheral metabolic pathophysiology.
*Pathophysiology of PCOS
*Current recommended treatments for PCOS
*Novel and emerging strategies for treatment of PCOS
*New treatments targeting androgen excess
*Clinical targeting of neuroendocrine dysfunction
-Modulation of kisspeptin
-Modulation of neurokinin B
-Modulation of dynorphin
*Treatments targeting insulin resistance
-Humanin
-Sodium glucose co-transporters (SGLT1, SGLT2)
-Incretin mimetics
Conclusion
There are a number of promising new therapies for PCOS emerging, which comprise a range of pharmacological strategies to target androgen excess, central neuroendocrine dysfunction, and/or metabolic pathophysiology (see Table 1). While there are no current AR antagonists approved for the treatment of PCOS, there is growing interest in the potential of therapeutic modulation of SHBG to manage hyperandrogenism. Recent evidence from clinical studies indicates that modulators of the KNDy neuronal network that target the central neuroendocrine pathophysiology of PCOS may also be incredibly useful therapeutic tools. Similarly, humanin, SGLT2 inhibitors, and incretin mimetics show promise in mitigating metabolic dysregulation in PCOS. These emerging PCOS therapies have the potential to improve patient outcomes in the future, beyond currently available strategies. However, further clinical investigations are needed to verify their efficacy and safety, particularly over the long term, and across PCOS phenotypes.
