PCOS - the many faces of a disorder in women and men

Purpose: Polycystic ovary syndrome (PCOS) is a very common endocrine, metabolic and reproductive disorder. The underlying pathophysiology is not yet fully understood and both genetic and environmental factors contribute to its development. We aimed to explore clinical and genetic aspects of familial clustering in PCOS, shedding light on its reproductive and metabolic consequences in both male and female first-degree relatives of the affected women.

Methods: Searching the electronic database of PubMed up to October 2023, we synthesized findings from available prospective and retrospective studies and review articles, investigating the familial clustering of PCOS and incorporating data on its metabolic consequences and genetic associations.

Results: There is a significant clustering of reproductive and metabolic abnormalities in first-degree relatives of women with PCOS. Genetic studies, including genome-wide association studies (GWAS), reveal a complex molecular etiology, emphasizing polygenic architecture. This is supported by the identification of two distinct PCOS subtypes, termed "reproductive" and "metabolic" which exhibit differential genetic underpinnings.

Conclusion: Clinicians should be aware of increased reproductive and metabolic dysfunction both in female and male first-degree relatives of PCOS probands. Current challenges include refining genetic risk scores and understanding the impact of PCOS genetic factors on diverse outcomes, necessitating a sex-specific approach in research and clinical practice. Future directions should address causality, improve diagnostic capability, and unravel the long-term consequences in both genders, emphasizing the importance of proactive clinical assessment in PCOS probands and their families.