New genetic insights could change how we treat, and talk about, PCOS

Emerging research indicates that polycystic ovary syndrome is part of a broader metabolic disorder affecting both men and women. 

Polycystic ovary syndrome (PCOS) has traditionally been understood as a reproductive health condition exclusively affecting women. New groundbreaking research conducted by Dr. Jia Zhu, an attending physician in the Division of Endocrinology, along with her research team, is fundamentally transforming this understanding. Their recent discoveries reveal that PCOS represents a comprehensive metabolic and reproductive disorder impacting both males and females, with genetic risk indicators detectable from early childhood.

The Metabolic Impact of PCOS

Previous research has demonstrated that children of both sexes born to mothers with PCOS can develop signs of cardiometabolic dysfunction from childhood onward. These manifestations include elevated obesity risk, insulin resistance, and dyslipidemia. Such findings indicate that PCOS genetics influence overall metabolic function across both sexes throughout their lifetime, extending far beyond reproductive health concerns.

Building upon existing research, Dr. Zhu and her team conducted an earlier study utilizing a polygenic risk score (PRS) to examine PCOS genetics more comprehensively. Their research revealed that elevated PRS levels correlated not only with increased PCOS risk in women but also with obesity, type 2 diabetes, coronary artery disease, and androgenic alopecia (male pattern baldness) in men. These findings further demonstrate the condition’s extensive metabolic health implications.

In their latest research, the team employed the PCOS PRS to identify metabolic, growth, and developmental signs of this underlying disorder during childhood and adolescence. Through analysis of data from four extensive pediatric cohorts, they discovered that genetic predisposition to PCOS correlates with elevated body mass index, increased fat mass, and altered peak height velocity in both boys and girls.

Significantly, these changes can emerge in children as young as 6 years old, occurring well before typical puberty onset. This timing suggests that PCOS genetic risk factors influence these characteristics independently of active ovarian function.

“Our research confirms that genetic predisposition to PCOS manifests in observable ways in both boys and girls, beginning in middle childhood,” Dr. Zhu states. “Through genetic analysis, we can identify individuals with risk factors for this condition before they reach reproductive maturity.”

Preventive Strategies and a Possible New Name

This research represents a paradigm shift in clinical understanding and management of PCOS, carrying significant implications for clinical practice, patient care, and potentially the condition’s nomenclature. By recognizing PCOS as a lifelong, systemic metabolic disorder, endocrinologists can transition from reactive treatment approaches to proactive, preventive strategies.

Dr. Zhu describes the practical applications of her team’s findings: “Our goal is to eventually develop these discoveries into clinical tools for risk prediction and targeted counseling for children at risk of developing PCOS and related health conditions later in life.” Early genetic identification and risk evaluation allow healthcare providers to implement personalized preventive strategies well before complications arise.

Dr. Zhu suggests that these preventive interventions could include careful monitoring of weight and growth patterns, earlier and more frequent insulin resistance screening, implementation of dietary modifications, and promotion of increased physical activity from early childhood. “Numerous lifestyle-specific interventions can be implemented to modify genetic risk,” she notes.

These findings suggest a future where PCOS could become a preventable condition rather than an unavoidable genetic outcome.

The Future of PCOS Research

Dr. Zhu and her colleagues are continuing their investigation into how PCOS-associated genetic factors influence pediatric health. Their current research focuses on understanding how maternal genetic risk for PCOS and the maternal-fetal environment impact a child’s probability of experiencing adverse birth and childhood outcomes.

“PCOS risk involves both direct genetic inheritance from mother to child—where a child inherits approximately 50% of their mother’s risk factors if she has PCOS—and the maternal-fetal environment,” Dr. Zhu explains. “Women with PCOS face higher risks for pregnancy complications including gestational diabetes and preeclampsia. Their intrauterine environment increases their child’s risk for adverse birth outcomes that can subsequently lead to metabolic complications later in life.”

The research team is analyzing population-based biobanks containing mother-child pairs to better comprehend how these genetic and environmental factors interact. Their findings could potentially create opportunities for risk assessment and intervention even before birth.

“In the future, this research could enable clinicians to perform genetic testing when a woman with PCOS, or at high risk for developing it, is pregnant or planning pregnancy. This would allow healthcare providers to potentially customize prenatal care counseling that could ultimately influence her child’s metabolic health outcomes.”

Learn more about the Division of Endocrinology at Boston Children’s Hospital