Polycystic Ovary Syndrome: Challenges and Possible Solutions

Abstract

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. This syndrome not only impairs female fertility but also increases the risk of obesity, diabetes, dyslipidemia, cardiovascular diseases, psychological diseases, and other health problems. Additionality, because of the high clinical heterogeneity, the current pathogenesis of PCOS is still unclear. There is still a large gap in precise diagnosis and individualized treatment. We summarize the present findings concerning the genetics, epigenetics, gut microbiota, corticolimbic brain responses, and metabolomics of the PCOS pathogenesis mechanism, highlight the remaining challenges in PCOS phenotyping and potential treatment approaches, and explain the vicious circle of intergenerational transmission of PCOS, which might provide more thoughts for better PCOS management in the future.

Keywords: pathogenesis; phenotype; polycystic ovary syndrome; treatment.

Figure 1

The pathological mechanisms of polycystic ovary syndrome. Great progress has been made in the etiological mechanism of PCOS, including genetics, epigenetics, microbiota, corticolimbic brain response, and metabolomics. Abbreviations: BCCA, branched-chain amino acid; DNA, Deoxyribonucleic acid; DNMT3A, DNA methyltransferases 3A; FFA, free fatty acid; FSHR, follicle-stimulating hormone receptor; INSR, insulin receptor; PCOS, polycystic ovary syndrome; TET, translocation methylcytosine dioxygenases. Components of this figure were created using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license (https://smart.servier.com).

Figure 2

The vicious circle of intergenerational transmission of PCOS. (a) Many challenges remain in the diagnosis and treatment of PCOS in reproductive age. The concurrent metabolic disturbances in PCOS will bring risks to both mother's and offspring's health. (b) Lifestyle intervention and metformin are the first-line treatment for PCOS and they are safe for use during conception. However, their efficiency in benefiting PCOS offspring requires more evidence to demonstrate. (c) The adverse uterine environment caused by maternal PCOS, according to the DOHaD theory, may increase the susceptibility to non-communicable diseases of their offspring. The offspring of PCOS are vulnerable to serval metabolic diseases in their early adult life, which will also affect their children's health. How to break this vicious cycle remains a huge challenge for the future. Abbreviations: BMI, body mass index; DOHaD, developmental origins of health and disease; PCOS, polycystic ovary syndrome. Components of this figure were created using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license (https://smart.servier.com).