Antimalarial compound opens path to treatment for polycystic ovary syndrome | Health and wellness

Artemis was, according to Greek mythology, the deity of hunting, childbirth and virginity, the protector of childbirth and fertility. Depicted in art with a bow in her hand and a fawn at her feet, the goddess also gave her name to an old plant with known medicinal properties: wormwood, which has a therapeutic effect against malaria and, according to recent research, may be superior to it. A scientific study that surprisingly combines science and mythology has revealed a new effect of the wormwood compound that more than ever resembles the fate of the goddess: an article published this Thursday in the journal The science suggests that a derivative of these plants may also relieve symptoms of polycystic ovary syndrome, a complex hormonal disorder that affects up to 13% of women of reproductive age and can cause, among other things, changes in the menstrual cycle. metabolic problems, acne or infertility.

Chinese medicine has known about the healing potential of plants of this genus for more than two thousand years. Artemisia: in the 16th century, for example, Qing Hao tea (Artemisia annual or sweet wormwood) to treat symptoms of malaria. Since then, science has studied these plants extensively to understand their properties and has discovered that one of their compounds, artemisinin, also has the ability to improve energy expenditure and insulin sensitivity. A new study from scientists at Fudan University (in Shanghai, China) takes a deeper look at these benefits and examines their effectiveness in treating polycystic ovary syndrome, a disorder associated with metabolic dysfunction and characterized by excessive production of androgens, a male symptom that is also common. although to a lesser extent in women. In animal experiments and a pilot study with 19 patients, scientists have proven that the artemisinin compound can stop excessive androgen production and thereby reduce the symptoms associated with this condition. This discovery opens the door to new treatments for a highly heterogeneous pathology with very limited therapeutic options.

Polycystic ovary syndrome is a common endocrine disease, one of the most common in gynecological consultations, explains Ana Robles, gynecologist at the Del Mar Hospital in Barcelona and specialist in endocrinology and human reproduction. “It is usually diagnosed in adulthood. Patients usually present for menstrual irregularities or fertility problems,” she says. An essential characteristic of this disease is the excessive production of androgens in the ovaries (hyperandrogenism), which causes a wide range of associated symptoms such as increased hair, alopecia, acne, irregular menstrual cycles or metabolic problems (high prevalence of this disease). obesity) among patients). In the long term, they also have a greater risk of cardiovascular disease, diabetes or hypertension. “Various pathways or causes of polycystic ovary syndrome have been described, but it is certainly multifactorial. There will be a genetic basis, it will be influenced by prenatal environmental factors and other situations, such as obesity,” explains Robles.

In addition, this is an extremely heterogeneous disease, and this is probably what makes it difficult to understand its origin, emphasizes Gemma Casals, gynecologist at the human reproduction department of the Hospital Clinic of Barcelona: “There are questions. It is not known how the syndrome develops, and there is speculation that it may not always develop in the same way,” he reflects.

To diagnose, Casals says, doctors look at “three cardinal points”: menstrual irregularities, the appearance of ovaries and rising androgen levels. These patients usually experience changes in the menstrual cycle, and the ovaries have a special morphology: they are usually larger in volume and have many antral follicles, which are a type of sac with immature eggs inside. Androgen excess is also confirmed by tests and scales that measure excess hair in more androgynous areas, such as the chin, buttocks or back.

The tools available to treat this clinical condition are limited and primarily focus on symptomatic relief. Thus, the recommendations for a healthy lifestyle and weight loss are supplemented primarily by contraceptives, which control hormone production, improve symptoms and regulate menstruation. But these treatment methods do not solve the problem comprehensively. They do not actually improve infertility or polycystic ovary morphology, the study authors add.

The versatility of artemisinins

In this context of limited therapeutic arsenal and limited efficacy, the Fudan University study opens the door to new treatment options and explores the versatility of artemisinin. “It has shown great promise in various applications with minimal side effects, such as treating malaria, colds, diarrhea, lupus and cancer. Our previous results showed that artemisinins promote metabolic homeostasis (balance) and protect against obesity, which prompted us to investigate whether they could regulate the development of polycystic ovary syndrome,” the authors explain in the paper.

Qi-qun Tang, the study’s principal investigator, explains in an email response that if androgen excess is the underlying cause of the disorder’s many characteristics, “controlling the excess is critical to intervention” in the disorder. And artemisinin can do this. In mice, scientists found that artemether, an artemisinin derivative, reduces ovarian androgen production by interfering with a key enzyme for producing these hormones. The results found “significant improvements,” the researchers noted, in the animals’ irregular cycles, polycystic ovary morphology, and low fertility.

The researchers then applied these initial findings to a small pilot clinical study of 19 women and found that when taking dihydroartemisinin (a drug used for malaria) for 12 weeks, PCOS biomarkers decreased and menstrual cycles normalized. “Our results highlight the promising potential of artemisinins as effective drugs for the comprehensive treatment of polycystic ovary syndrome,” the authors conclude in the scientific paper. However, the researchers acknowledge some limitations in the study, such as the animal model used does not accurately reproduce “the complex conditions of polycystic ovary syndrome in women.”

Forward Approach

In an analysis accompanying the study, Elisabeth Stener-Victorin, a researcher in the Department of Physiology and Pharmacology at Karolinska Institutet in Sweden, believes that the discovery of artemisinins as a treatment for PCOS symptoms is a “promising approach” to this pathology. “This achievement not only highlights the versatility of artemisinins, but also has great potential to improve the quality of life for millions of affected women, representing an important advance in reproductive medicine,” he reflects. In a similar vein, Robles, who was also not involved in the study, adds: “This is a pilot clinical study, but anything that is fundamental research into the mechanisms and knowing what proteins and enzymes are involved opens the door to developing targeted drugs.” to improve treatment.”

For his part, Casals, who has also published a study on the effects of bariatric surgery in obese patients with PCOS on reducing symptoms of this hormonal disorder, argues that Tang’s study is a first step and, although more confirmatory studies are needed, it is “good news.” . “This compound not only reduces testosterone levels, which is a major androgen, but also reduces menstrual cycles and polycystic ovaries. And in animal models it is possible to improve the implantation of embryos. The authors also conduct a pathophysiological study and determine why they work: the artemisinin-inhibiting enzyme affects androgens,” he explains.

Maria Jesús Cancelo, a spokeswoman for the Spanish Society of Gynecology and Obstetrics, said Tang’s study represents an “interesting approach.” “Current treatments are based on treating symptoms, and the authors propose treating the cause by reducing the production of androgens by the ovary itself. The investigation is very initial and we have to be careful, but it seems very promising,” he assesses. Tan says they are currently “extending the follow-up period (for study participants) to determine whether relapse occurs after a long period without medication.” They are also working to refine the dose and duration of treatment so they can begin a larger study later.

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