Genetic Variants Linked to Increased Testosterone Production in Women with PCOS Identified

Recent research has uncovered specific DNA variations responsible for elevating testosterone levels in women diagnosed with polycystic ovary syndrome (PCOS), a prevalent hormonal disorder. The study focused on the gene DENND1A, which plays a crucial role in hormone regulation within reproductive tissues. Using advanced human cell models that mimic PCOS conditions, scientists discovered that activating certain genetic regulatory regions within DENND1A leads to increased gene expression, ultimately boosting testosterone production. This provides the first direct evidence that inherited genetic variants can cause the hormonal imbalance characteristic of PCOS. The findings were published in Nature Communications and shed light on the biological mechanisms underlying PCOS, a condition affecting 10-15% of women at reproductive age worldwide. Elevated testosterone levels are a hallmark of PCOS, contributing to symptoms like unwanted hair growth and fertility issues. Prior investigations had mapped broad genome regions associated with the disorder, but this study pinpointed specific regulatory DNA elements that influence gene activity.

By employing CRISPR-based epigenome editing, the research team demonstrated that turning these DNA switches on in hormone-producing cells increases DENND1A expression and testosterone output, offering a mechanistic link between genetic variation and disease phenotype. This precision approach narrows down the focus to potential therapeutic targets, opening avenues for treatments aimed at modulating gene activity rather than just managing symptoms. While DENND1A was a key locus identified, the research explored over 1,000 regulatory DNA elements across 14 PCOS-linked regions, revealing multiple potential targets involved in hormone regulation. These insights could lead to innovative interventions that address the root genetic causes of PCOS and related hormonal abnormalities.

The study emphasizes that inherited DNA variants are significant contributors to the hormonal dysregulation seen in PCOS. Understanding the genetic basis of increased testosterone production paves the way for personalized therapies and enhances biological understanding of this complex disorder. Future research aims to expand these discoveries across more genetic regions and diverse populations, ultimately aiming to develop targeted treatments that can significantly improve outcomes for women with PCOS.

Source: https://medicalxpress.com/news/2025-08-dna-variants-testosterone-production-pcos.html