Artemis was, according to Greek mythology, the deity of hunting, births and virginity, protector of childbirth and fertility. Depicted in art with a bow in her hand and a fawn at her feet, the goddess has also given her name to an old plant with known medicinal properties: artemisia, with therapeutic effects against malaria and, according to recent research, may beyond it. In a surprising crossover between science and mythology, a scientific study has illuminated a new effect of an artemisia compound that evokes, more than ever, the fate of the goddess: an article published this Thursday in the journal Science suggests that a derivative of these plants also has the potential to alleviate the 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, alterations in the menstrual cycle. , metabolic problems, acne or infertility.
Chinese medicine has been aware, for more than two millennia, of the healing potential of plants of the genus Artemisia: in the 16th century, for example, it was recommended qing hao tea (Artemisia annua or sweet wormwood) to treat the symptoms of malaria. Since then, science has scrutinized these plants to understand their properties and has revealed that one of their compounds, artemisinin, also has the ability to improve energy expenditure and insulin sensitivity. The new study by researchers at Fudan University (in Shanghai, China) delves into these benefits and examines their competence in treating polycystic ovary syndrome, a disorder linked to metabolic dysfunction and characterized by the excessive production of androgens, male hormones that are also produced, although to a lesser extent, in women. In experiments with animals and in a pilot trial with 19 patients, scientists have proven that an artemisinin compound manages to stop the excessive production of androgens and, thereby, reduce the symptoms associated with this condition. The discovery opens the door to a new treatment for a very heterogeneous pathology with very limited therapeutic options.
Polycystic ovary syndrome is a common endocrine disorder, one of the most common in gynecology consultations, explains Ana Robles, a gynecologist at the Hospital del Mar in Barcelona and a specialist in endocrinology and human reproduction. “It is usually diagnosed in adulthood. Patients usually consult for menstrual disorders or fertility problems,” she says. The essential characteristic of this disorder 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 (there is a high prevalence of obesity). among patients). In the long term, they also have a greater risk of cardiovascular disease, diabetes or hypertension. “Different pathways or causes of polycystic ovary syndrome have been described, but it is surely multifactorial. There will be a genetic basis and intrauterine environmental factors and other situations will influence it, such as obesity,” explains Robles.
Furthermore, it is a tremendously heterogeneous disorder and, probably, that is what makes it difficult to understand its origin, emphasizes Gemma Casals, a gynecologist in the Human Reproduction section of the Hospital Clínic of Barcelona: “There are questions. It is not well known how the syndrome develops and there is speculation that perhaps it does not always develop the same way,” she reflects.
For the diagnosis, says Casals, doctors look at “three cardinal points”: menstrual cycle disorders, the appearance of the ovaries and the increase in androgens. In these patients, there are usually alterations in menstruation and the ovaries have a particular morphology: they are usually larger in volume and have many antral follicles, which are a type of sac with immature eggs inside. Excess androgens are also confirmed by tests and scales that measure excess hair in more androgynous areas, such as the chin, buttocks or back, for example.
The tools available to treat this clinical condition are limited and are fundamentally aimed at relieving symptoms. Thus, to the recommendation of healthy lifestyle habits and weight reduction, contraceptives are added, above all, which control hormonal production, improve symptoms and regulate menstruation. But these treatments do not solve the problem comprehensively. In fact, they do not improve infertility or the morphology of the polycystic ovary, the authors of the study add.
The versatility of artemisinins
In this context of a limited therapeutic arsenal and limited efficacy, the Fudan University study opens the door to a new avenue of treatment and explores the versatility of artemisinin. “It has shown great promise in various applications with minimal adverse effects, such as the treatment of malaria, cold, diarrhea, lupus erythematosus and cancer. Our previous findings showed that artemisinins promoted homeostasis [equilibrio] metabolic and protected against obesity, which led us to investigate whether they could regulate the development of polycystic ovary syndrome,” the authors justify in the article.
Qi-qun Tang, principal investigator of the study, explains in an email response that if excess androgens are the main driver of numerous characteristics of this disorder, “controlling the excess is crucial to intervene” in this pathology. And artemisinin can do it. In mice, scientists discovered that artemether, a derivative of artemisinin, reduces the production of ovarian androgens by affecting a key enzyme for the manufacture of these hormones. As a result, “considerable improvements” were found, the research points out, in irregular cycles, the morphology of the polycystic ovary and the low fertility of the animals.
The scientists then took these initial findings to a small pilot clinical trial with 19 women and found that by taking dihydroartemisinin (a medication used for malaria) for 12 weeks, PCOS biomarkers were reduced and menstrual cycles were reduced. they normalized. “Our findings highlight the promising potential of artemisinins as effective drugs for the comprehensive treatment of polycystic ovary syndrome,” the authors conclude in the scientific article. The researchers admit, however, some limitations in the research, such as the animal model used, which does not exactly replicate “the complex conditions of polycystic ovary syndrome in women.”
Promising approach
In an analysis accompanying the study, Elisabet Stener-Victorin, a researcher at the Department of Physiology and Pharmacology at the Karolinska Institute in Sweden, considers that the discovery of artemisinins as a remedy against the symptoms of polycystic ovary is a “promising approach” in this pathology. “This advance not only highlights the versatility of artemisinins, but also has great potential to improve the quality of life of millions of affected women, representing an important advance in reproductive medicine,” she reflects. Along the same lines, Robles, who has not participated in the research either, adds: “It is a pilot clinical trial, but everything that is basic research on the pathways and knowing which proteins and enzymes are involved opens the door to designing target drugs for improve treatment.”
For his part, Casals, who has also published A study on the impact of bariatric surgery in patients with obesity and polycystic ovary syndrome to reduce the symptoms of this hormonal disorder, maintains that Tang’s study is a first step and, although more confirmatory research is required, it is “good news.” . “This compound not only reduces testosterone levels, which is the main androgen, but also reduces menstrual cycles and the polycystic appearance of the ovary. And in animal models, it manages to improve embryo implantation. The authors also end up doing a pathophysiological study and determining why they work: the enzyme that inhibits artemisinin has effects on androgens,” he explains.
María Jesús Cancelo, spokesperson for the Spanish Society of Gynecology and Obstetrics, points out that Tang’s study presents “an interesting approach.” “The current availability of treatments is based on treating the symptoms and what these authors propose is to treat the cause, to reduce the production of androgens from the ovary itself. The investigations are very initial and we must be cautious, but it seems very promising,” she says. Tang assures that, currently, they are “extending the observation period [a las participantes del estudio] to determine if there is a relapse after a longer period without the medication.” In addition, they are working to refine the dose and duration of treatment to later begin a larger trial.
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