How does artemisinin, a compound from Traditional Chinese Medicine (TCM) plant Artemisia get involved with PCOS management?
Artemisinin has been shown to be able to modulate testosterone and insulin.
The challenge of diagnosing and managing PCOS
Polycystic ovarian syndrome (PCOS) is one of the most common reproductive endocrine disorders that affects 10 to 13% of women in their reproductive age, with notably higher prevalence rates in South Asian countries. Although there is no single test to specifically diagnose PCOS, healthcare professionals typically start with a discussion of symptoms and these symptoms typically consist of the ovarian cysts, irregular menstrual periods, and often, excess hair growth on the face and body. PCOS is also often associated with metabolic disorders. It is a major risk factor for obesity, type 2 diabetes, and heart disease. It is also a leading cause of infertility. Yet despite how common it is, PCOS has no cure and few approved treatments, though a few early-stage clinical trials are underway.
Treatment options for PCOS usually include lifestyle changes such as weight loss regimes, and medications such as oral contraceptives, insulin-sensitising agents, and antiandrogens to help manage symptoms. Surgery can be considered to treat fertility problems related to PCOS, though the effectiveness varies among individuals. In a newly published study, scientists found that a derivative of artemisinin- a compound from Artemisia plants, which have been used for several hundred years to treat malaria in China, helped relieve PCOS symptoms in rats and a small group of women. In this article, we delve into the insights of the new study to explore its implications for clinical practice and patient management.
What are some possible causes of PCOS?
The exact cause of PCOS is unknown, but various factors that play a role include:
- Androgen Excess: Androgen excess, particularly testosterone, plays a central role in various phenotypic features of PCOS, including follicular dysplasia, impaired ovulation, endometrial conditions, and metabolic dysfunction. Additionally, prenatal androgen exposure can lead to PCOS-like traits in female offspring, increasing the transgenerational risk of PCOS. Therefore, effective management of androgen excess is essential for PCOS intervention.
- Insulin resistance: Blood sugar levels rise when cells are insulin-resistant. This also results in the body making more insulin to compensate. Insulin excess can lead to weight gain, irregular menstrual periods, and might also cause the body to make too much testosterone. One visible sign of insulin resistance is the presence of dark, velvety patches of skin on areas like the neck, armpits, groin, or under the breasts.
- Hereditary: Research indicates that specific genes may be associated with PCOS susceptibility, particularly genes that contribute to hormonal imbalances, insulin resistance, inflammation, and other PCOS-related traits. Having a family history of PCOS influences the likelihood of developing this condition. While genetics alone do not determine PCOS, understanding family history can provide valuable insights for early detection and personalised management.
- Low-grade Inflammation: Research consistently demonstrates that individuals with PCOS exhibit higher levels of specific inflammatory markers in their blood. This chronic inflammation, although less intense than acute inflammation, persists over time and can impact various aspects of health. Low-grade inflammation contributes to the production of androgens by the polycystic ovaries. These androgens can lead to complications such as heart and blood vessel problems.
What is artemisinin?
Artemisinin is a compound from Artemisia annua used in traditional Chinese medicine to treat malaria, reduce fever, and reduce swelling. The most common ethnobotanical usage of this plant involves using whole plant decoction to treat cold, malaria, and cough.
Why artemisinin?
The researchers in the study had previously demonstrated that artemisinin, the compound from Artemisia, and its derivatives exhibited the ability to enhance energy expenditure and improve insulin sensitivity. Through its mechanisms in activating thermogenic adipocytes (fat cells), artemisinin and its derivatives contribute to protecting against diet-induced obesity and metabolic disorders. Since obesity and insulin resistance are major risk factors for PCOS, the authors went on to investigate the therapeutic potential of artemisinins in both rodent PCOS-like models and human patients with PCOS. They evaluated the impact of artemisinin derivatives on testosterone levels, estrous cycles, and polycystic ovarian morphology.
Insights from the study
The study highlights artemisinins’ potential as effective drugs for comprehensive PCOS treatment, revealing a novel mechanism that artemisinins represses ovarian testosterone synthesis.
- Clinical Findings: In rodent PCOS models, the artemisinin analog, artemether, improved hyperandrogenemia, irregular estrous cycles, and polycystic ovarian morphology. A pilot clinical trial showed that dihydroartemisinin treatment effectively reduced hyperandrogenemia, reduced anti-Müllerian hormone levels, improved polycystic ovarian morphology, and normalised menstruation in patients with PCOS.
- Mechanism of Action: CYP11A1 converts cholesterol into pregnenolone, which serves as the precursor for various steroid hormones, including oestrogen, testosterone, aldosterone, and cortisol. Artemisinins were found to ameliorate PCOS symptoms by enhancing the interaction between proteins LONP1 and CYP11A1, leading to the degradation of CYP11A1 and inhibition of ovarian androgen synthesis.
The study also offers a new approach to managing hyperandrogenism and PCOS occurrence by targeting the LONP1-CYP11A1 interaction.
Comparing the effectiveness of artemisinin derivatives and current treatments in PCOS
The treatment landscape for PCOS is diverse, encompassing lifestyle modifications, pharmacological interventions, and occasionally surgical options. Among the pharmacological options, oral contraceptives and insulin-sensitising agents have been the mainstay treatments. Oral contraceptives primarily address the hormonal imbalance in PCOS by reducing androgen levels, thereby mitigating symptoms like hirsutism (excessive hair growth in a male-like pattern) and acne and restoring regular menstruation. Insulin-sensitising agents, such as metformin, target metabolic aspects of PCOS, improving insulin sensitivity and often leading to weight loss and normalised menstrual cycles. In contrast, artemisinin derivatives, as revealed in the recent study, not only address hyperandrogenemia but also show promising results in reversing polycystic ovarian morphology and normalising menstruation. This suggests that artemisinin could offer a more comprehensive management of PCOS by targeting both the endocrine and metabolic facets of the disorder.
Conclusion
PCOS remains one of the most pervasive endocrine disorders affecting women of reproductive age. Despite its prevalence and the significant health risks it poses, PCOS continues to be a condition with no cure and limited treatment options. Artemisinin derivatives introduce a compelling perspective in the treatment of PCOS by targeting both metabolic and endocrine dysfunctions, showing potential advantages over traditional treatments like oral contraceptives, which primarily address hormonal imbalances, and insulin-sensitising agents such as metformin, which focus on metabolic symptoms. Moving forward, the success of artemisinin derivatives will hinge on further clinical validation, understanding their long-term impacts, and integrating them into personalised treatment plans that address the multifaceted nature of PCOS. The ongoing research into these compounds, specifically targeting the LONP1-CYP11A1 interaction, highlights the potential to significantly improve patient outcomes, offering a promising pathway for advancing the management of PCOS.
References
- Alzate, S. (2023, October 3). PCOS is Genetic, Showing an Increased Prevalence in South Asian Countries. Medical Channel Asia. https://medicalchannelasia.com/pcos-is-genetic-showing-an-increased-prevalence-in-south-asian-countries/
- Tan, R. (2023, March 8). Understanding PCOS on International Women’s Day: Symptoms, Solutions, and Hope. Medical Channel Asia. https://medicalchannelasia.com/understanding-pcos-on-international-womens-day-symptoms-solutions-and-hope/
- Teede, H. J., Tay, C. T., Laven, J. J. E., Dokras, A., Moran, L. J., Piltonen, T. T., Costello, M. F., Boivin, J., Redman, L. M., Boyle, J. A., Norman, R. J., Mousa, A., & Joham, A. E. (2023). Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Journal of Clinical Endocrinology & Metabolism. Advance online publication. https://doi.org/10.1210/clinem/dgad463
- Mayo Clinic. (2022, September 8). Polycystic ovary syndrome (PCOS). https://www.mayoclinic.org/diseases-conditions/pcos/symptoms-causes/syc-20353439
- Wani, K. I., et al. (2022). Artemisia annua L.: Traditional Uses, Phytochemistry, and Pharmacological Activities. In H. P. Devkota & T. Aftab (Eds.), Medicinal Plants of the Asteraceae Family. Springer, Singapore.
- Liu, Y., et al. (2024). Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction. Science, 384(eadk5382). https://doi.org/10.1126/science.adk5382
