Metabolic Syndrome as Driver for Gynecological Cancer: Systematic Review and Meta-Analysis Finds

The systematic review and meta-analysis were published in the Indian Journal of Medical Research in October 2025.

Metabolic syndrome represents a complex multifactorial condition (obesity, hyperglycemia, and hypertension), while its specific contribution to gynecological oncology has remained inconsistent in earlier reports. Consequently, Indra Kundu, of the ICMR-National Institute of Research in Reproductive and Child Health, Mumbai, Maharashtra, India, and colleagues conducted the review, aiming to systematically quantify the risks of gynecological cancers among women with metabolic syndrome.

The systematic review and meta-analysis evaluated 25 observational studies involving women aged 18 and older with MetS, defined by the World Health Organization (WHO) or International Diabetes Federation (IDF) as having at least three out of five standard metabolic abnormalities. The researchers assessed diverse populations—ranging from 1,000 to 600,000 participants—while strictly excluding individuals with significant comorbidities, sarcomas, or a history of malignancy to maintain diagnostic specificity. Primary and secondary endpoints for various reproductive tract cancers were quantified using random-effects models to pool the odds ratio (OR), hazard ratio (HR), relative risk (RR), and standardised incidence ratio (SIR)

Key Clinical Findings of the Study:

• Uterine and Endometrial Cancer Risk: MetS is most strongly linked to uterine and endometrial cancer, with data showing a pooled OR of 1.99 in case-control studies and a significant 1.45 HR in cohort investigations.
• Ovarian and Cervical Malignancy Association: Clinical evidence indicates that metabolic disturbances are associated with a 3.44-fold increased odds of ovarian cancer and a consistent 1.27 HR for the development of cervical cancer.
• Risks in Rare Gynecological Sites: Metabolic dysfunction also extends to less common malignancies, with research demonstrating an elevated hazard for both vaginal cancer (HR 1.54) and vulvar cancer (HR 1.49).
• Impact of Diagnostic Criteria: The degree of identified cancer risk varies by the diagnostic framework applied, with the IDF criteria revealing a higher risk for endometrial cancer compared to the Harmonized Definition (HD) or the Adult Treatment Panel III (ATP III).
• Hormonal and Pathophysiological Drivers: The increased cancer risk is largely driven by hyperinsulinemia suppressing sex hormone-binding globulin (SHBG), which raises circulating estrogen and facilitates a pro-inflammatory, proliferative environment conducive to malignancy.

The findings reveal that women diagnosed with metabolic syndrome face a consistently heightened risk of gynecological malignancies (endometrial, ovarian, cervical, vaginal, and vulvar cancers) by creating a pro-inflammatory environment where insulin resistance suppresses SHBG, leading to elevated circulating hormones that stimulate reproductive tissues, regardless of the specific diagnostic criteria or study design employed.

The review suggests that clinicians should focus on primary metabolic prevention and rigorous cancer screening to reduce the risk of these malignancies.

Reference

Kundu I, John D, Ansari I, Pavithran K, Idicula-Thomas S. Risk of gynecologic cancers in women with metabolic syndrome: A systematic review & meta-analysis. Indian J Med Res 2025; 162: 197-210