PCOS and genetics: A study opens new treatment perspectives.

Polycystic Ovary Syndrome (PCOS) is one of the most common conditions among women of reproductive age. It affects up to 10–15% and manifests with menstrual cycle irregularities, ovulatory difficulties, acne, weight gain, and in many cases, an excess of androgen hormones such as testosterone. It is a condition that affects not only reproductive health but also emotional well-being and quality of life.

In recent years, research has sought to understand why PCOS develops and what the underlying causes of hyperandrogenism are. A recent study conducted by the Mount Sinai Health System in collaboration with Duke University and published in Nature Communications (August 2025) has identified a key piece: genetic variants in the DENND1A gene seem to directly increase testosterone production.

This is a result that does not yet change clinical practice, but it helps to better understand the mechanisms of PCOS and paves the way for future personalized therapies.

What is PCOS and why is testosterone mentioned?

PCOS is not a single disease but a complex condition that involves hormonal, genetic, and metabolic factors. It is characterized by:

Irregular or absent cycles.

Ovaries with numerous small follicles visible on ultrasound.

Increased androgen (testosterone) levels in the blood or clinical symptoms.

Hyperandrogenism is one of the most recognizable traits: it causes acne, hair growth in typically male areas, and sometimes hair loss. But most importantly, it impacts ovulation, making conception difficult.

Until now, we knew that PCOS had a genetic component, but it was unclear how genes directly influenced testosterone production.

The Mount Sinai–Duke University Study.

The research team, coordinated by Laavanya Sankaranarayanan and Andrea Dunaif, analyzed 14 regions of DNA already associated with PCOS through previous genetic studies. Among these, the focus was on DENND1A, a gene suspected to play a key role.

Using innovative molecular biology techniques, the researchers have:

Identified small non-coding variants (i.e., those that don’t directly change proteins but regulate how genes function).

Used epigenetic editing tools to "turn on" or "turn off" these variants in human cells.

Observed how hormone production changed in response.

The most relevant result? When the regulatory variants linked to DENND1A were activated, the cells produced more testosterone.

What does this discovery really mean?

The novelty is important because, for the first time, the research shifted from statistical observation ("these variants are more frequent in women with PCOS") to functional evidence: those variants can actually increase testosterone.

However, it is important to be clear and cautious:

The study focused only on one of the approximately 30 genes associated with PCOS.

The tests were conducted in the lab, not yet in large-scale clinical studies.

Currently, there are no therapies available that directly target DENND1A.

In other words: it’s an advance in understanding PCOS, not an immediately available cure.

Why could this make a difference in the future?

Knowing the role of genes allows research to:

Imagine more targeted therapies, capable of reducing excess androgens at their source.

Develop personalized medicine strategies: knowing whether a patient has certain variants could, one day, guide treatment choices.

Scientifically validate what many women experience: PCOS is not “the result of lifestyle” or willpower, but has concrete biological foundations.

These are still distant perspectives, but they are important for raising awareness and combating stigma.

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If living with PCOS raises questions for you, or you want better guidance regarding symptoms, diagnosis, and possible treatments, the Mater Clinic team is available to provide information, advice, and personalized support.

📱 WhatsApp: 645 096 548

📧 Email: care@mater.clinic

🌐Website: www.mater.clinic

Sources:

Sankaranarayanan et al., Nature Communications, August 18, 2025.

Mount Sinai Health System, press release, August 29, 2025.

Duke University, review of research projects in reproductive endocrinology.