Plant-derived compounds best known for their antimalarial properties relieve polycystic ovary syndrome, a major public health problem that affects millions of women worldwide. These compounds, called artemisinins, achieve their affect by suppressing ovarian androgen production in multiple rodent models as well as in a small cohort of human patients, according to a new study. The findings not only underscore the versatility of artemisinins but reveal a promising new approach for preventing and treating the disorder.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. It is characterized by elevated androgen levels (hyperandrogenemia) and associated with a wide range of health impacts, including metabolic dysfunction, impaired ovulation, and often infertility. However, despite the high prevalence of the syndrome, the mechanistic basis of PCOS is poorly understood, and drug treatments often focus only on specific symptoms with limited effectiveness.

Because hyperandrogenemia is the main feature and cause of most PCOS-associated symptoms and comorbidities, treatments aimed at suppressing androgen production could be beneficial in treating PCOS.

Here, the researchers evaluated the effect of artemisinin and its derivatives on PCOS development. While better known for their antimalarial effects, these compounds have also been shown to have beneficial metabolic effects.

In rodent models, the authors found that artemether (ATM), an artemisinin derivative isolated from Artemisia plants, reduces ovarian androgen synthesis by targeting CYP11A1, a crucial enzyme in androgen production.

ATM induces CYP11A1 degradation by enhancing its interaction with the protease LONP1. And, LONP1 overexpression, the authors found, suppresses ovarian androgen production.

In a pilot clinical study of 19 women with PCOS, the authors further demonstrated the therapeutic potential of artemisinin. For these women, taking dihydroartemisinin – a drug used to treat malaria – for 12 weeks substantially reduced key PCOS biomarkers and led to more regular menstrual cycles without side effects.

“Although further studies will be needed to fully understand the long-term effects and to optimize dosing strategies to maximize therapeutic outcomes, the discovery of artemisinins as effective remedies for PCOS nonetheless represents a promising new approach for the development of specific therapies that will potentially change the landscape of PCOS treatment,” writes an author in a related Perspective.

https://www.science.org/doi/10.1126/science.adk5382